虚拟实验系统在医学机能实验学教学中的应用
作者:
张弛;曾勇智;张海涛;易光辉
期刊:
教育教学论坛 ,2013年(33):265-266 ISSN:1674-9324
作者机构:
南华大学 医学院机能学实验中心,湖南 衡阳,421001
关键词:
机能实验学;虚拟实验;真实实验
摘要:
医学机能实验学是基础医学领域的一门实验课程,继承了生理学、药理学和病理生理学实验课程的实验教学内容。在机能实验教学中构建虚拟实验室是为了适应社会发展,本文对其在机能实验中的应用进行了研究与探讨。
语种:
中文
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血清淀粉样蛋白A对THP-1巨噬细胞炎症反应及SR—BI表达的影响
作者:
朱明燕;陈意;赵国军;石金凤;龙治峰;...
期刊:
中国动脉硬化杂志 ,2013年21(9):I0052-I0053 ISSN:1007-3949
作者机构:
南华大学医学院组织学与胚胎学教研室南华大学附属第二医院心血管内科,湖南省衡阳市421001
会议名称:
第十二次全国动脉硬化性疾病学术会议
会议时间:
2013-10-11
会议地点:
江苏苏州
会议论文集名称:
第十二次全国动脉硬化性疾病学术会议论文集
关键词:
B类I型清道夫受体;血清淀粉样蛋白A;THP-1巨噬细胞
摘要:
目的 观察血清淀粉样蛋白A(SAA)对THP-1巨噬细胞B类Ⅰ型清道夫受体(SR-BI)及炎症因子MCP-1、TNF-α、CRP、IL-1表达的影响,初步探讨SAA在巨噬细胞炎症反应中的作用及机制。方法 以不同浓度(0、50、100、200、400及800 μg/L)的SAA处理THP-1巨噬细胞24h,或以400 μg/L的SAA处理细胞不同时间(0、4、8、16、24及32 h),或以400 μg/L的SAA分别与p38激动剂amsomycin或抑制剂SB203580共同处理细胞24 h,分别采用RT-PCR检测SR-BI、炎症因子MCP-1、TNF-α、CRP及IL-1 mRNA的表达,Western blot及细胞免疫组织化学检测SR-BI、磷酸化p38蛋白、炎症因子蛋白的表达。结果 与对照组相比,SAA处理细胞后,炎症因子的mRNA及蛋白表达上调,而SR-BI mRNA及蛋白的表达受到抑制,并且磷酸化p38蛋白的表达也上调,这种效应呈浓度和时间依赖性。与SAA单独处理组比较,SAA与p38激动剂anisomycin共同处理细胞后,其SR-BI表达下调,炎症因子及磷酸化p38蛋白表达增加;而SAA与p38抑制剂SB203580共同处理细胞后,其SR-BI表达增加,炎症因子及磷酸化p38蛋白表达减少。结论 SAA增加THP-1巨噬细胞炎症因子的表达,抑制SR-BI的表达,促进THP-1巨噬细胞炎症反应;SAA的作用可能与p38蛋白的磷酸化有关,p38 MAPK信号途径可能参与了SR-BI的表达调节及SAA刺激的THP-1巨噬细胞炎症反应。
语种:
中文
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内脂素对人脐静脉内皮细胞通透性的影响及机制
作者:
曾颖;张青海;李晨曦;李媛彬;熊升林;...
期刊:
中国动脉硬化杂志 ,2013年21(9):I0048-I0049 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化学湖南省重点实验室,湖南省衡阳市421001
会议名称:
第十二次全国动脉硬化性疾病学术会议
会议时间:
2013-10-11
会议地点:
江苏苏州
会议论文集名称:
第十二次全国动脉硬化性疾病学术会议论文集
关键词:
内脂素;缝隙连接蛋白;磷酸肌醇3激酶;细胞外调节蛋白激酶1;p38丝裂原活化蛋白激酶
摘要:
背景与目的 内脂素是一种来源于内脏脂肪的新脂肪因子,具有复杂的生物学功能,除具有类似胰岛素的降血糖效应外,还可能作为炎症介质参与体内炎症反应.大量证据表明内脂素可能在心脑血管疾病、糖尿病、代谢综合征和肾脏疾病等动脉粥样硬化性疾病中发挥着重要作用,这与内脂素影响斑块稳定性、血管炎症及糖脂代谢等作用密切相关.近年来,研究认为它可能是一个替在危险因素参与了内皮功能紊乱的发生.然而,内脂素对血管内皮功能的影响非常复杂,到目前为止,一直没有直接证据证实内脂素能导致动脉内皮损伤及其作用机制.本研究从内皮细胞间连接角度出发,拟观察内脂素对人脐静脉内皮细胞通透性及缝隙连接蛋白Connexin37(Cx37)、Connexin40 (Cx40)和Connexin43(Cx43)表达的影响及初步探讨其可能机制.方法 将HUVEC12细胞以5×104/孔的密度种板,经不同浓度(0、1、10、100 nmol/L)和不同时间(0、3、6、12、24h)内脂素处理,或预先Wortmannin(50 nmol/L)、U0126 (50 μmol/L)、SB203580 (50 μmol/L)等抑制剂孵育3h.运用实时荧光定量PCR和Western blot分别检测Cx37、Cx40和Cx43 mRNA与蛋白水平的变化,并采用Transwell system检测单层内皮细胞通透性的改变.结果 内脂素处理内皮细胞对Cx37、Cx40 mRNA表达无影响,但Cx37、Cx40蛋白的表达随着内脂素浓度的增高和时间的延长而减少,呈一定剂量、时间依赖性.然而,内脂素能呈剂量、时间依赖性上调Cx43 mRNA和蛋白的表达.通透性实验结果显示,随着内脂素浓度的增加及处理时间的延长,内皮细胞致密单层的通透性逐渐增大,且该作用呈剂量和时间依赖性.此外,Wortmannin特异性抑制磷酸肌醇3激酶(PI3K)活性后,能明显逆转内脂素诱导的Cx43蛋白表达,但对Cx43的mRNA表达无影响.U0126特异性抑制ERK1/2活性或SB203580特异性抑制p38MAPK活性则均能明显下调内脂素诱导的Cx43 mRNA及蛋白表达.结论 内脂素可下调内皮细胞Cx37、Cx40蛋白表达,上调Cx43的表达;内脂素可增加内皮细胞的通透性,且呈时间、剂量依赖性;PI3K、ERK1/2及p38丝裂原活化蛋白激酶(p38MAPK)经不同方式介导内脂素诱导HUVEC-12内皮细胞Cx43的表达.
语种:
中文
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S1P通过S1PRl/3对THP-1源性巨噬细胞胆固醇代谢的调控作用及机制
作者:
张智超;刘行;张大棣;伍荣;鲁艳菊;...
期刊:
中国动脉硬化杂志 ,2013年21(9):I0047-I0047 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化学湖南省重点实验室,湖南省衡阳市421001
关键词:
鞘氨醇-1-磷酸;鞘氨醇-1-磷酸受体;ATP结合盒转运体A1;胆固醇流出;动脉粥样硬化
摘要:
背景与目的鞘氨醇.1.磷酸(S1P)作为一种信号鞘磷脂,介导HDL诸多生物功能如抗动脉粥样硬化、抗血栓和保护血管内皮等。S1P通过其5个受体(S1PRl-S1PR5)激活细胞内复杂的信号转导通路实现生物功能多样化。其中S1PRl/3在细胞增殖、血管发生和重建、神经形成、免疫细胞迁移、炎症反应、内皮细胞屏障功能等方面发挥重要作用。本研究主要探讨S1P通过S1PRl/3对THP-1源性巨噬细胞胆固醇流出的调控作用及其信号机制。方法佛波酯(PMA)诱导THP-1单核细胞24h后,选择不同时间和浓度的SIP进行处理,人胆固醇ELISA试剂盒检测细胞培养液中胆固醇含量。
语种:
中文
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Regulation of metabolism and transport of sphingosine-1-phosphate in mammalian cells
作者:
Liu, Xing;Zhang, Qing-Hai;Yi, Guang-Hui*
期刊:
Molecular and Cellular Biochemistry ,2012年363(1-2):21-33 ISSN:0300-8177
通讯作者:
Yi, Guang-Hui
作者机构:
[Liu, Xing; Yi, Guang-Hui] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qing-Hai] Univ S China, Clin Res Inst, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Yi, Guang-Hui] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词:
Sphingosine-1-phosphate;Ceramide;Sphk;ABC transporter;SR-B1
摘要:
Sphingosine-1-phosphate (S1P), which is generated from the sphingosine kinase-catalyzed phosphorylation of sphingosine, is now recognized as a critical regulator of many kinds of physiological and pathological processes, including cancer, cardiovascular function, and diabetes. It can also trigger a wide variety of biological effect, such as cell movement, differentiation, survival, inflammation, immunity, calcium homeostasis, and angiogenesis. As we know, a number of the biological effects of S1P are mediated by its binding to five specific G protein-coupled receptors located on the cell surface or intracellular targets. However, the synthesis and the secretion of S1P are regulated by various endogenetic or ectogenous stimuli and involve many kinds of enzymes and transporters. In this review, we discuss the regulation of S1P synthesis by many kinds of enzymes and mainly introduce the process of ceramide to S1P. Moreover, S1P deterioration is important balance in physiologic adjustment. We also describe the role of verified or potential transporters in S1P release in detail.
语种:
英文
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NO-1886 ameliorates glycogen metabolism in insulin-resistant HepG2 cells by GSK-3β signalling
作者:
Wang, Zong-bao;Zeng, Huai-cai;Wei, Han-song;Yi, Guang-hui;Yu, Jian;...
期刊:
Journal of Pharmacy and Pharmacology ,2012年64(2):293-301 ISSN:0022-3573
通讯作者:
Yin, Wei-dong
作者机构:
[Zhang, Ya-li; Yin, Wei-dong; Wang, Zong-bao; Yi, Guang-hui; Wang, Yue-ting] Univ S China, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Yu, Jian; Wang, Zong-bao] Univ S China, Dept Lab Anim Sci, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Huai-cai] Univ S China, Sch Publ Hlth, Hengyang 421001, Hunan, Peoples R China.;[Wei, Han-song] Ninghe Cty Hosp, Dept Lab Med, Tianjin, Peoples R China.
通讯机构:
[Yin, Wei-dong] U;Univ S China, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词:
glycogen synthesis;GSK-3 ss;insulin resistance;lipoprotein lipase;NO-1886
摘要:
Objectives The aim of the study was to elucidate the possible role and mechanism of NO-1886 (ibrolipim, a lipoprotein lipase activator) in ameliorating insulin resistance induced by high palmitate. Methods HepG2 cells were cultured in RPMI 1640 medium and were treated with palmitate to induce insulin resistance. Free fatty acids (FFAs), glucose, glycogen, cell viability and mRNA and protein levels were analysed separately. Key findings We found that HepG2 cells treated with 0.5 mm palmitate for 48 h led to a significant decrease of insulin-induced glucose consumption (from 2.89 ± 0.85 mm in the control to 0.57 ± 0.44 mm in palmitate). Insulin resistance (IR) of HepG2 cells was induced by 0.5 mm palmitate for 48 h. NO-1886 stimulated glucose consumption, glycogen synthesis and FFA absorption in insulin-resistant HepG2 cells. Maximum stimulation effects were observed with 10 μm NO-1886 for 24 h. Compared with the dimethyl sulfoxide-treated group, 2.5 μm NO-1886 or higher could induce the mRNA expression of lipoprotein lipase. Meanwhile, NO-1886 increased the protein content of P-GSK-3βser 9 and decreased the protein level of GSK-3β in insulin-resistant HepG2 cells, but NO-1886 didn't change the protein levels of PI3-Kp85 and Akt2. Conclusion Lipoprotein lipase activator NO-1886 could increase glycogen synthesis in HepG2 cells and could ameliorate the insulin resistance, which was associated with GSK-3 signalling. © 2011 Royal Pharmaceutical Society.
语种:
英文
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An involvement of SR-B1 mediated PI3K–Akt–eNOS signaling in HDL-induced cyclooxygenase 2 expression and prostacyclin production in endothelial cells
作者:
Zhang, Qing-Hai;Zu, Xu-Yu;Cao, Ren-Xian;Liu, Jiang-Hua;Mo, Zhong-Cheng;...
期刊:
Biochemical and Biophysical Research Communications ,2012年420(1):17-23 ISSN:0006-291X
通讯作者:
Yi, Guang-Hui
作者机构:
[Liu, Xing; Xiong, Sheng-Lin; Zeng, Ying; Li, Yuan-Bin; Zhang, Qing-Hai; Mo, Zhong-Cheng; Yi, Guang-Hui] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Qing-Hai; Cao, Ren-Xian; Zu, Xu-Yu; Liu, Jiang-Hua] Univ S China, Affiliated Hosp 1, Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Yi, Guang-Hui] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词:
COX-2;ENOS;HDL;PGI 2;PI3K;SR-B1
摘要:
It is well-known that sphingosine-1-phosphate (S1P), the phospholipid content of HDL, binding to S1P receptors can raise COX-2 expression and PGI 2 release through p38MAPK/CREB pathway. In the present study we assess the action of SR-B1 initiated PI3K-Akt-eNOS signaling in the regulation of COX-2 expression and PGI 2 production in response to HDL. We found that apoA1 could increase PGI 2 release and COX-2 expression in ECV 304 endothelial cells. Furthermore, SR-B1 was found to be involved in HDL induced up-regulation of COX-2 and PGI 2. Over-expressed SR-B1 did not significantly increase the expression of COX-2 and the PGI 2 levels, but knock-down of SR-B1 by siRNA could significantly attenuate COX-2 expression and PGI 2 release together with p38MAPK and CREB phosphorylation. Consistently, the declines of p-p38MAPK, p-CREB, COX-2 and PGI 2 were also observed after incubation with LY294002 (25μmol/L; PI3K special inhibitor) or L-NAME (50μmol/L; eNOS special inhibitor). In addition, we demonstrated the increases of PGI 2 release, COX-2 expression and p38MAPK phosphorylation, when nitric oxide level was raised through the incubation of L-arginine (10 or 20nmol/L) in endothelial cells. Taking together, our data support that SR-B1 mediated PI3K-Akt-eNOS signaling was involved in HDL-induced COX-2 expression and PGI 2 release in endothelial cells. © 2012 Elsevier Inc.
语种:
英文
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ABCA1, ABCG1, and SR-BI: Transit of HDL-associated sphingosine-1-phosphate
作者:
Liu, Xing;Xiong, Sheng Lin;Yi, Guang-Hui*
期刊:
Clinica Chimica Acta ,2012年413(3-4):384-390 ISSN:0009-8981
通讯作者:
Yi, Guang-Hui
作者机构:
[Liu, Xing; Yi, Guang-Hui] Univ S China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang, Hunan, Peoples R China.;[Xiong, Sheng Lin] You Cty People Hosp, Zhuzhou, Hunan, Peoples R China.
通讯机构:
[Yi, Guang-Hui] U;Univ S China, Key Lab Atherosclerol Hunan Prov, Inst Cardiovasc Res, Hengyang, Hunan, Peoples R China.
关键词:
ABCA1;HDL;S1P;Sphingolipids;SR-BI
摘要:
Sphingosine-1-phosphate (S1P) is a zwitterionic lysophospholipid generated by the sphingosine kinase-catalyzed phosphorylation of sphingosine. A number of the biological effects of S1P are mediated by its binding to five specific G protein-coupled receptors located on the cell surface or intracellular targets. However, the synthesis and secretion of S1P require release out of cells for binding with receptors by certain transporters and carriers. High-density lipoprotein (HDL) is an important carrier of S1P in the blood, but the mechanism by which it does so is unclear. This review discusses the mechanism how S1P is transported, and focuses particularly on how the formation of HDL-associated S1P (HDL-S1P) is mediated by certain transporters and carriers. A hypothesis that the ATP-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B memberI (SR-BI) play pivotal roles in HDL-S1P formation is also described. © 2011 Elsevier B.V.
语种:
英文
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Calphostin C抑制脂肪分化相关蛋白诱导的ACAT1表达
作者:
袁中华;陶媛;刘清南;黄谙非;刘晓辉;...
期刊:
中国动脉硬化杂志 ,2012年20(12):1057-1063 ISSN:1007-3949
作者机构:
[袁中华; 陶媛; 唐朝克; 易光辉; 王佐] 南华大学心血管疾病研究所;[刘清南] 益阳医学高等专科学校护理系基础护理学教研室;[黄谙非] 深圳市西丽医院病理科;[刘晓辉] 苏州大学唐仲英血液学研究中心;[田国平] 南华大学附属第二医院心内科
关键词:
脂肪分化相关蛋白;乙酰辅酶A:胆固醇酰基转移酶1
摘要:
目的我们已经发现adipophilin通过改变乙酰辅酶A∶胆固醇酰基转移酶1(ACAT1)的表达来促进细胞内脂质蓄积,病理状态下形成泡沫细胞,成为动脉粥样硬化的始动因素。本研究旨在探讨该过程所涉及的信号通路,阐明adipophilin引起细胞内脂质积聚的机制。方法通过克隆adipophilin基因,构建逆转录病毒载体pQCXIP-HA-Adi,使用siRNA技术构建pSuper-retro-adipophilin siRNA逆转录病毒载体,包装病毒后,感染RAW264.7细胞,筛选后获得高或低表达adipophilin的细胞。将该细胞分别与300 nmol/L PKC抑制剂Calphostin C孵育16 h或同时再加入50 mg/L氧化型低密度脂蛋白(ox-LDL)共孵育,应用RT-PCR和Western blot检测细胞内ACAT1的表达。当低表达adipophilin的细胞与Calphostin C共孵育时,在不同的时间点取样,RT-PCR和Westernblot检测各时间点细胞内ACAT1的表达。结果高表达adipophilin细胞中ACAT1表达增加,低表达adipophilin细胞中ACAT1表达减少。无论在高或低表达adipophilin的细胞中,Calphostin C能够抑制ACAT1的表达,与不孵育Calphostin C组相比差别有显著性。与ox-LDL孵育使高表达adipophilin的细胞荷脂,同样能够发现Calphostin C抑制ACAT1的表达。低表达adipophilin的细胞与Calphostin C共孵育1 h后,ACAT1 mRNA开始下降;孵育8 h后,ACAT1蛋白开始下降;孵育16 h后ACAT1 mRNA及蛋白表达均明显下降,与对照组相比差别有显著性。高及低表达adipophilin或负荷脂质状态下,Calphostin C能够时间依赖性的抑制ACAT1的表达。结论adipophilin引起细胞内脂质积聚的机制可能是,PKC信号分子作用于adipophilin,并进一步影响ACAT1的表达,最终导致细胞内脂质积聚。
语种:
中文
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Knowledge of stroke warning signs and risk factors among patients with previous stroke or TIA in China
作者:
Zeng, Ying;He, Guo-Ping* ;Yi, Guang-Hui;Huang, Yan-Jin;Zhang, Qing-Hai;...
期刊:
Journal of Clinical Nursing ,2012年21(19-20):2886-2895 ISSN:0962-1067
通讯作者:
He, Guo-Ping
作者机构:
[Zeng, Ying; He, Guo-Ping] Cent S Univ, Sch Nursing, Changsha, Hunan, Peoples R China.;[Zeng, Ying; Huang, Yan-Jin] Univ S China, Sch Nursing, Hengyang, Hunan, Peoples R China.;[Yi, Guang-Hui] Univ S China, Sch Med, Inst Cardiovasc Dis, Hengyang, Hunan, Peoples R China.;[Zhang, Qing-Hai] Univ S China, Affiliated Hosp 1, Hengyang, Hunan, Peoples R China.;[He, Ling-Ling] Univ S China, Affiliated Hosp 2, Hengyang, Hunan, Peoples R China.
通讯机构:
[He, Guo-Ping] C;Cent S Univ, Sch Nursing, Changsha, Hunan, Peoples R China.
关键词:
emergency treatment;knowledge;risk factors;stroke;transient ischaemic attacks;warning signs
摘要:
Aims and objectives. The purpose of this study was to describe knowledge about stroke warning signs and risk factors in patients with previous stroke or transient ischaemic attacks in China and to investigate the relationship between socio-demographic characteristics & health status and patients' knowledge about stroke. Background. Stroke is the leading cause of death and functional impairment in China. Survivors are at high risk of new vascular events. Secondary prevention after stroke or transient ischaemic attacks is not satisfactory. Previous research suggests that awareness of stroke plays an important role in facilitating secondary prevention. However, little is known about knowledge of stroke warning signs and risk factors among patients with previous stroke/transient ischaemic attacks. Design. A cross-sectional questionnaire study. Methods. This study was conducted in Hunan Province, China, between July and December in 2010. Subjects were recruited using a cluster sampling method. A questionnaire was administered to 1600 patients with stroke/transient ischaemic attacks diagnose from eight hospitals, and 1200 patients (75%) responded. Patients' knowledge about stroke warning signs and risk factors were collected and analysed. Results. Patients' knowledge about stroke warning signs was very poor (only 3·3% identified all warning signs and 28·3% identified three). Patients' knowledge about important risk factors (e.g. atrial fibrillation, diabetes, metabolic syndrome, etc.) was also very poor (<30%). Patients' action in emergency was extremely poor (only 9·2% reported to call emergency service). The age, education, stroke-related diagnoses and family history of cardiovascular disease were significantly associated with patients' knowledge about stroke. Conclusions. Knowledge about stroke warning signs and risk factors was very poor in patients with previous stroke or transient ischaemic attacks in China. Relevance to clinical practice. Dissemination of stroke knowledge should be a core responsibility for Chinese clinical nurse. Future clinical education to improve patient's knowledge about stroke and further intervention to manage cardiovascular risk factors are indicated. © 2012 Blackwell Publishing Ltd.
语种:
英文
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ATP Citrate Lyase Inhibitors as Novel Cancer Therapeutic Agents
作者:
Zu, Xu-Yu;Zhang, Qing-Hai;Liu, Jiang-Hua;Cao, Ren-Xian;Zhong, Jing;...
期刊:
Recent Patents on Anti-Cancer Drug Discovery ,2012年7(2):154-167 ISSN:1574-8928
通讯作者:
Pizzorno, Giuseppe
作者机构:
[Zhong, Jing; Quan, Zhi-Hua; Zhang, Qing-Hai; Cao, Ren-Xian; Zu, Xu-Yu; Liu, Jiang-Hua] Univ S China, Affiliated Hosp 1, Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Pizzorno, Giuseppe] Desert Res Inst Summerlin, Human Hlth & Environm Program, Las Vegas, NV 89135 USA.;[Yi, Guang-Hui] Univ S China, Sch Med, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;[Pizzorno, Giuseppe] Desert Res Inst Summerlin, Human Hlth & Environm Program, 10530 Discovery Dr, Las Vegas, NV 89135 USA.
通讯机构:
[Pizzorno, Giuseppe] D;Desert Res Inst Summerlin, Human Hlth & Environm Program, 10530 Discovery Dr, Las Vegas, NV 89135 USA.
关键词:
ACL inhibitors;ATP citrate lyase;Hydroxycitrate;Non-hydroxycitrate Citric Acid Analogues;Posttranslational regulation;Transcriptional regulation;cancer therapy;citrate;lipogenesis;small chemicals
摘要:
ATP citrate lyase (ACL or ACLY) is an extra-mitochondrial enzyme widely distributed in various human and animal tissues. ACL links glucose and lipid metabolism by catalyzing the formation of acetyl-CoA and oxaloacetate from citrate produced by glycolysis in the presence of ATP and CoA. ACL is aberrantly expressed in many immortalized cells and tumors, such as breast, liver, colon, lung and prostate cancers, and is correlated reversely with tumor stage and differentiation, serving as a negative prognostic marker. ACL is an upstream enzyme of the long chain fatty acid synthesis, providing acetyl-CoA as an essential component of the fatty acid synthesis. Therefore, ACL is a key enzyme of cellular lipogenesis and potent target for cancer therapy. As a hypolipidemic strategy of metabolic syndrome and cancer treatment, many small chemicals targeting ACL have been designed and developed. This review article provides an update for the research and development of ACL inhibitors with a focus on their patent status, offering a new insight into their potential application.
语种:
英文
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AOPPs Inhibits Cholesterol Efflux by Down-regulating ABCA1 Expression in a JAK/STAT Signaling Pathway-Dependent Manner
作者:
Mo, Zhong-Cheng;Xiao, Ji;Liu, Xie-Hong;Hu, Yan-Wei;Li, Xiao-Xu;...
期刊:
Journal of Atherosclerosis and Thrombosis ,2011年18(9):796-807 ISSN:1340-3478
通讯作者:
Tang, Chao-Ke
作者机构:
[Tang, Chao-Ke; Li, Xiao-Xu; Hu, Yan-Wei; Liu, Xie-Hong; Tang, Ya-Ling; Mo, Zhong-Cheng; Yi, Guang-Hui; Wang, Zuo; Xiao, Ji] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
通讯机构:
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词:
Advanced oxidation protein products;ATP-binding cassette transporter A1;JAK/STAT;Cholesterol efflux
摘要:
AIMS: Advanced oxidation protein products (AOPPs) are new independent risk factor for coronary artery disease. This study was to determine the effects and potential mechanisms of AOPPs on cholesterol efflux from human macrophage foam cells. METHODS: Human THP-1 monocytes were preincubated with Phorbol-12-myristate- 13-acetate (PMA) and oxidized low density lipoprotein (ox-LDL) to form foam cells. The protein and mRNA expression were examined by western immunoblotting assays and real-time quantitative PCR, respectively. Cellular cholesterol content was measured by HPLC. The cholesterol efflux was assessed by liquid scintillation counting. RESULTS: AOPPs significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and liver X receptor alpha (LXRalpha) and reduced cholesterol efflux from THP-1 macrophage- derived foam cells. AOPPs substantially activated NADPH oxidase and activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal pathway in THP-1-derived foam-like cells. Inhibiting NADPH oxidase by diphenyliodonium (DPI) effectively abolished the AOPPs-induced decrease in cholesterol efflux and the expression of ABCA1. Inhibiting JAK/STAT activation by its specific inhibitor AG-490 or by siRNA could also block AOPPs action on THP-1 cells. CONCLUSIONS: AOPPs may first down-regulate the expression of LXRalpha and ABCA1 through JAK/STAT signal pathway activation and then inhibit cholesterol efflux in THP-1-derived foam-like cells; therefore, our study may be useful for understanding the critical effects of AOPPs on the pathogenesis of atherosclerosis.
语种:
英文
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ciglitazone对巨噬细胞CD36表达及胆固醇流入的影响
作者:
莫中成;陈欣;龙治峰;曾颖;张青海;...
期刊:
细胞与分子免疫学杂志 ,2011年27(6):685-687 ISSN:1007-8738
通讯作者:
Mo, Z.C.
作者机构:
[莫中成; 龙治峰] 南华大学:医学院组织胚胎学教研室;[陈欣; 曾颖; 张青海; 易光辉] 南华大学:心血管病研究所
通讯机构:
Department of Histoplogy and Embryology, University of South China, China.,
关键词:
过氧化物酶体增殖物激活型受体-γ;环格列酮;动脉粥样硬化
摘要:
目的:观察过氧化物酶体增殖物激活型受体γ(PPARγ)的激动剂ciglitazone对THP-1巨噬细胞CD36表达及细胞胆固醇流入的影响.方法:以THP-1巨噬细胞为研究对象,用50 mg/L氧化低密度指蛋白(oxLDL)分别与不同浓度的PPAγ激动剂ciglitazone(0、5、10、15 μmol/L)共同孵育THP-1巨噬细胞24 h后,采用液体闪烁计数法检测[3H]胆固醇流入,采用逆转录-聚合酶链式反应和Western blot分别检测CD36的表达.结果:oxLDL及不同浓度的ciglitazone 与THP-1巨噬细胞共孵育后,与对照组比较(20.3%),加ciglitazone的处理组胆固醇流入随着浓度的增加而依次增加,分别为28.6%、37.2%、44.3%、48.7%,细胞CD36的表达上调.结论:ciglitazone可上调THP-1巨噬细胞CD36的表达,并增加细胞胆固醇流入.
语种:
中文
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HSP27对雌激素诱导的内皮保护作用的影响
作者:
周琴;张青海;李媛彬;熊升林;刘行;...
期刊:
中国动脉硬化杂志 ,2011年(3):256 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化学湖南省重点实验室
关键词:
人脐静脉内皮细胞;雌激素;热休克蛋白27;一氧化氮;细胞间黏附分子1
摘要:
目的观察雌二醇(E2)及雌激素受体拮抗剂他莫昔芬对HUVEC HSP27表达的影响,以及HSP27 siRNA对雌激素内皮保护作用的影响。方法分别用不同浓度(10-9、10-8和10-7mol/L)E2处理HUVEC 24 h;10-7mol/L雌二醇及10-6mol/L他莫昔芬处理HUVEC 24 h。以空白组为阴性对照,RT-PCR和Western blot检测HSP27的表达。分别转染HSP27 siRNA和mockRNA48 h后,再与10-7mol/L E2孵育24 h。空白组做为阴性对照,RT-PCR和Western blot检测HSP27的表达;分别用硝酸还原酶法和ELISA检测培养基中NO和内皮素1的含量;ELISA检测细胞表面细胞间黏附分子1(ICAM-1)的含量。结果 E2处理HUVEC可上调HSP27的mRNA和蛋白表达水平,并且具有剂量依赖性,表达的峰值在10-7mol/L。10-6mol/L他莫昔芬可阻断10-7mol/L E2的作用。RT-PCR、Western blot检测HSP27 siRNA序列能明显下调HSP27mRNA及蛋白的表达。HU-VEC转染HSP27 siRNA48 h后再与10-7mol/LE2孵育24 h,能显著减弱E2对内皮细胞分泌NO和ICAM-1的影响,而对内皮素1没有明显影响。结论雌二醇呈剂量依赖性诱导HUVEC产生HSP27增加,雌激素受体途径参与HSP27诱导的内皮细胞ICAM-1和NO的改变。
语种:
中文
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硫化氢对THP-1源性巨噬细胞脂质摄取的影响
作者:
赵战芝;姜志胜;易光辉;谭建苗;邓华菲;...
期刊:
中国动脉硬化杂志 ,2011年19(2):85-88 ISSN:1007-3949
作者机构:
[赵战芝; 姜志胜; 易光辉; 谭建苗; 索荣] 南华大学心血管病研究所;[邓华菲] 湘南学院病理生理教研室
关键词:
硫化氢;THP-1源性巨噬细胞;氧化型低密度脂蛋白;脂质摄取
摘要:
目的探索硫化氢对THP-1源性巨噬细胞脂质摄取的影响及可能机制。方法 采用荧光显微镜测DiI标记的氧化型低密度脂蛋白(DiI-OX-LDL)摄取、RT-PCR和免疫印迹法测定CD36 mRNA和蛋白表达。结果 巨噬细胞与DiI-OX-LDL孵育后大量摄取氧化型低密度脂蛋白(OX-LDL),外源性硫化氢供体硫氢化钠显著抑制巨噬细胞摄取氧化型低密度脂蛋白,而炔丙基甘氨酸(一个硫化氢产生酶胱硫醚-r-裂解酶抑制剂)加剧巨噬细胞摄取氧化型低密度脂蛋白。进而,硫氢化钠呈浓度依赖性抑制巨噬细胞CD36 mRNA和蛋白表达,而炔丙基甘氨酸促进巨噬细胞CD36 mRNA和蛋白表达。结论硫化氢抑制巨噬细胞摄取脂质及清道夫受体CD36表达。
语种:
中文
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肥厚型心肌病的分子遗传机制
作者:
何仗群;匡泽民;易光辉
期刊:
中国医药指南 ,2011年09(34):282-285 ISSN:1671-8194
作者机构:
南华大学心血管疾病研究所,动脉硬化学湖南省重点实验室,湖南,衡阳,421001;郴州市第一人民医院,湖南,郴州,423000
关键词:
心肌病;肥厚型;基因;信号转导;分子遗传
摘要:
家族性肥厚型心肌病是一种常染色体显性遗传病。肥厚型心肌病临床表现存在很大差异,从无症状到黑朦、晕厥、胸痛、心律失常及心力衰竭等不尽相同。很多青年患者往往平时无症状或首发症状就是猝死。已发现至少有25种基因的突变可导致家族性肥厚型心肌病。加深对其分子遗传学的认识有利于促进该病的诊断和治疗。本文对家族性肥厚型心肌病的近期分子遗传学研究进行了总结。
语种:
中文
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SR-B1依赖PI3K-Akt-eNOS信号途径的激活介导HDL诱导内皮细胞PGI2释放
作者:
张青海;李媛彬;熊升林;刘行;周琴;...
期刊:
中国动脉硬化杂志 ,2011年(3):259-260 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化学湖南省重点实验室
关键词:
B类Ⅰ型清道夫受体;磷酸肌醇3-激酶;内皮型一氧化氮合酶;环氧合酶2;前列环素
摘要:
目的观察SR-B1介导HDL诱导内皮细胞PGI2生成的信号激活途径。方法分别转染pcDNA3.1(-)-hSR-B1重组表达质粒或SR-B1 siRNA48 h后,30 mg/L HDL孵育24 h;30 mg/L apoA1与ECV304内皮细胞共孵育24 h;分别用25μmol/L PI3K特异性抑制剂LY294002或50μmol/L eNOS特异性抑制剂L-NAME预处理3 h后,30 mg/L HDL孵育24 h。空白组作为阴性对照,30 mg/L HDL处理组为阳性对照,RT-PCR和/(或)Western blot检测PGIS、COX-2、CREB及磷酸化CREB的表达;免疫细胞化学法检测内皮细胞中COX-2蛋白的表达;ELISA法检测培养液中6-keto-PGF1α的生成。结果不管是mRNA水平还是蛋白水平,在过表达SR-B1后,HDL均不能显著上调COX-2的表达,然而,有趣地是siRNA沉默SR-B1后,可见HDL诱导内皮细胞COX-2的表达明显减少,且免疫细胞化学检测能得到相似的结果。30 mg/L apoA1孵育内皮细胞24 h后,COX-2表达亦出现增加。但是,不管是HDL单独处理还是过表达或沉默SR-B1,PGIS的表达都没有明显变化。抑制剂单独处理细胞对PGI2的生成没影响,但抑制PI3K或eNOS活性后可明显减少HDL诱导的PGI2生成,其中以抑制PI3K活性后,PGI2生成减少更为显著;同样,LY294002或L-NAME对HDL诱导内皮细胞COX-2、磷酸化CREB表达的影响与影响PGI2的生成呈相同效果,特异性抑制PI3K和特异性抑制eNOS活性均能下调HDL诱导的COX-2表达及CREB磷酸化,且同样以抑制PI3K后下调幅度更为明显。结论 HDL诱导内皮细胞PGI2释放依赖SR-B1与其介导的胞内PI3K-Akt-eNOS信号途径的激活有关。
语种:
中文
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HDL上调脐静脉内皮细胞COX-2表达依赖鞘鞍醇激酶2和1-磷酸鞘鞍醇受体途径
作者:
熊升林;张青海;刘行;李媛彬;周琴;...
期刊:
中国动脉硬化杂志 ,2011年(03):256 ISSN:1007-3949
作者机构:
南华大学心血管疾病研究所动脉硬化学湖南省重点实验室
关键词:
高密度脂蛋白;鞘鞍醇激酶2;1-磷酸鞘氨醇;环氧合酶2;免疫共沉淀
摘要:
目的研究HDL通过1-磷酸鞘鞍醇受体途径上调COX-2表达的细胞内信号机制。方法培养人脐静脉内皮细胞,HDL不同时间和浓度处理,qPCR和WB检测COX-2、CREB和Sphk2表达情况。人脐静脉内皮细胞转染SiRNASphk2后,qPCR和WB检测HDL对COX-2表达情况。人脐静脉内皮细胞用采用JTE(抑制S1P2)、PTX(抑制Gi/o)、SB203580(抑制p38MAPK)、Stau-rosporine(抑制PKC)及U0126(抑制ERK1/2)抑制剂处理后,qPCR和WB检测HDL对COX-2的表达情况。免疫共沉淀检测p-CREB和Sphk2结合情况,用激光共聚焦进行定位观察。结果 HDL呈时间和剂量上调COX-2、SphK2表达及CREB磷酸化,转染SphK2siRNA后COX-2表达水平下调;采用JTE(抑制S1P2),SB203580(抑制P38MAPK),Staurosporine(抑制PKC),U0126(抑制ERK1/2)抑制剂处理后,HDL对COX-2的上调作用明显抑制;免疫共沉淀和激光共聚焦显示p-CREB和SphK2结合。结论 HDL通过S1P2-G i/o-PKC(P38MAPK/ERK)-SphK2?p-CREB途径影响COX-2的表达。HDL激活内皮细胞核内鞘鞍醇激酶和使CREB磷酸化,从而上调COX-2的表达。
语种:
中文
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构建医学机能实验课第二课堂的组织形式与现实意义
作者:
张弛;姜志胜;易光辉;屈顺林;韦星;...
期刊:
医学教育研究与实践 ,2010年18(4):770-772 ISSN:2096-3181
作者机构:
南华大学,医学院,机能学实验中心,湖南,衡阳,421001;南华大学,医学院病理生理学教研室,湖南,衡阳,421001;南华大学,医学院生理学教研室,湖南,衡阳,421001
关键词:
机能实验课;第二课堂;教学改革
摘要:
高校充分发挥第二课堂在人才创新培养体系的主阵地作用,不断提升第二课堂效能,是实现创新人才培养目标的现实要求。本文阐述了医学机能实验课第二课堂开展的组织形式及其现实意义。
语种:
中文
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致心律失常性右室心肌病的病因与发病机制
作者:
申惠龙;李媛彬;易光辉
期刊:
茶:健康天地 ,2010年4(10):19-20,22 ISSN:1002-431X
作者机构:
衡阳,南华大学心血管疾病研究所动脉硬化学湖南省重点实验室,湖南,421001
关键词:
致心律失常性右室心肌病;基因突变;发病机制
摘要:
致心律失常性右室心肌病是一种病因复杂的遗传性心肌病,临床上甚至导致致命性心律失常,尤其在年轻人和运动员.该病的病理组织学特征是右室心肌被纤维或/和脂肪组织取代,以至于发生早期室性心律失常和晚期心力收缩减弱和心衰.目前已经发现了8个致病基因与本病相关,其中有5个是桥粒蛋白编码基因(PG,PKP2,DP,DSG2,DSC2),表明桥粒蛋白基因突变越来越被关注和认识.本文对致心律失常性右室心肌病(ARVC)的病因与发病机制做一综述.
语种:
中文
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