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黄连提取物对ApoE基因敲除小鼠主动脉易损斑块Perilipin和PPAR-γ基因表达的影响
引用本文:周明学,徐浩,陈可冀,温见燕,潘琳,郭艳茹.黄连提取物对ApoE基因敲除小鼠主动脉易损斑块Perilipin和PPAR-γ基因表达的影响[J].中国中西医结合杂志,2008,28(6):532-536.
作者姓名:周明学  徐浩  陈可冀  温见燕  潘琳  郭艳茹
作者单位:1. 中日友好医院全国中西医结合心血管病中心,北京,100029
2. 中日友好医院全国中西医结合心血管病中心,北京,100029;中国中医科学院西苑医院心血管病中心
3. 中日友好医院临床研究所中心实验室
基金项目:国家自然科学基金 , 国家重点基础研究发展计划(973计划)
摘    要:目的 观察黄连提取物对ApoE基因敲除小鼠动脉粥样硬化(AS)易损斑块内周脂素(perilipin)和过氧化物酶体增殖物激活受体γ(PPAR-γ)基因表达的影响,探讨黄连提取物稳定AS斑块的作用及可能机制。方法 33只6~8周龄ApoE基因敲除小鼠予高脂饮食喂养13周,待其形成成熟的AS斑块后,随机分为3组:模型组、黄连提取物组、辛伐他汀组(阳性对照组),每组11只。继续高脂喂养,并按体重比折算给予小鼠临床推荐剂量的相应药物治疗13周,处死动物,每只小鼠分别取主动脉根部的4个切面,分别行HE染色和Movat染色,观察并计算各组小鼠主AS斑块内埋藏纤维帽的平均数目,实时荧光定量PCR法检测主动脉内perilipin和PPAR-γmRNA的表达。结果 给药13周后,黄连提取物组斑块内埋藏纤维帽的数目与模型组比较明显减少(P<0.05),并且斑块内perilipin mRNA的表达与模型组比较显著降低(P<0.05),而PPAR-γmRNA的表达较模型组显著增加(P<0.01)。结论 在临床推荐剂量上,黄连提取物可显著减少ApoE基因敲除小鼠主动脉粥样斑块破裂次数,有助于稳定易损斑块,其机制可能与促进小鼠AS斑块内PPAR-γmRNA表达,抑制perilipin mRNA表达有关。

关 键 词:黄连提取物    周脂素  过氧化物酶体增殖物激活受体γ    动脉粥样硬化    斑块破裂  易损斑块
修稿时间:2007年10月15

Effect of Coptis Root Extract on Gene Expressions of Perilipin and PPAR-γ in Aortic Vulnerable Athernsclerotic Plaque of ApoE-gene Knockout Mice
Authors:ZHOU Ming-xue  XU Hao  CHEN Ke-ji
Institution:National Integrative Medicine Center for Cardiovascular Diseases, China-Japan Friendship Hospital, Beijing.
Abstract:OBJECTIVE: To observe the effect of coptis root extract (CRE) on the gene expressions of perilipin and peroxisome proliferator activated receptor gamma (PPAR-gamma) in atherosclerotic plaque of ApoE-gene knockout mice for exploring its plaque stabilizing action and possible mechanism. METHODS: Thirty-three ApoE knockout mice, 6-8 weeks old, were fed with high-fat diet for 13 weeks. After mature atherosclerotic plaques being formed, the animals were randomly allocated into the control group, the CRE group, and the simvastatin group (as positive control) , 11 in each group. They were continuously fed with high-fat diet and to the two drug-treated groups, respective drugs in clinically recommended dose were given for another 13 weeks. Then all mice were sacrificed by the end of experiment. The morphology and composition of atherosclerotic plaques in 4 sections of aortic roots were examined with HE and Movat stain, the average number of fibrous caps buried in the plaque was observed and counted, and the gene expressions of perilipin and PPAR-gamma mRNA were determined by Real-time fluorescent quantitative PCR technology. RESULTS: After treatment for 13 weeks, the number of fibrous caps and the gene expression of perilipin mRNA in the CRE group was significantly lower (P<0.05), but gene of PPAR-gamma mRNA was higher (P<0.01) than those in the model group. CONCLUSION: In a clinically recommended dose, CRE can significantly decrease the frequency of plaque rupture in aorta of ApoE-gene knockout mice and do favour to plaque stability, its mechanism may be related to the promotion of PPAR-gamma mRNA expression and the inhibition of perilipin mRNA expression.
Keywords:coptis root extract  perilipin  PPAR-γ  atherosclerosis  plaque rupture  vulnerable plaque
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