白藜芦醇对动脉粥样硬化兔Fas/FasL凋亡途径的影响

目的:探讨白藜芦醇对兔动脉粥样硬化斑块内细胞凋亡及Fas、FasL、Caspase-3基因转录的影响.方法:成熟健康雄性新西兰白兔70只,适应性喂养10 d后随机分为5组:A组继续喂普通饲料;B组喂高脂饲料;C、D、E组喂高脂饲料的同时分别给予白藜芦醇4 mg·kg~(-1)·d~(-1)、8 mg·kg~(-1)·d~(-1)、16 mg·kg~(-1)·d~(-1)进行干预.末端脱氧核苷酸转移酶介导的脱氧三磷酸尿苷缺口末端标记法(TUNEL)检测细胞凋亡;逆转录聚合酶链式反应法(RT-PCR)检测Fas、FasL、Caspase-3mRNA转录水平.结果:高脂喂养12周后,成功建立动脉粥样硬化模型;病理对照组斑块内有大量的凋亡细胞;与病理对照组比较,正常对照组血管内膜偶见少量的凋亡细胞(P<0.01),低至高剂量白藜芦醇干预组细胞凋亡依次降低(P<0.05),其Fas mRNA、FasL mRNA转录水平也依次降低,白藜芦醇高剂量组Fas mRNA转录水平与正常对照组比较差异无统计学意义(P>0.05).结论:白藜芦醇可抑制动脉粥样斑块内细胞凋亡,从而稳定斑块、抑制动脉粥样病变进展,这一作用可能通过抑制Fas/FasL凋亡途径,降低Caspase-3基因转录来实现,并具有一定的量效关系.

Effects of resveratrol on Fas/FasL apoptotic pathway in rabbits with atherosclerosis

Objective:To investigate the effect of resveratrol on FasmRNA, FasLmRNA and Caspase-3mRNA transcription in rabbits with atherosclerosis.Method:Seventy male New Zealand white rabbits were randomly divided into 5 groups:A normal control group,B pathological control group, C pathological control group treated with low dosage resveratrol(4mg·kg~(-1)·d~(-1)),D pathological group teated with mid dosage resveratrol(8 mg·kg~(-1)·d~(-1))and E pathological group treated with high dosage resveratrol(16mg·kg~(-1)·d~(-1)).At the end of the 12th week, apoptotic cells were detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. The mRNA expression of Fas, FasL and caspase-3 was examined by RT-PCR. The analysis of ANOVA by SSPS software package was used to analyses the data.Result:The atherosclerosis model with rabbits had been successfully established with high fat diet. Apoptotic index in group B was significantly increased when compared to group A (P<0.01). Resveratrol inhibited apoptosis of cells in atherosclerotic plaque. There were large quantity of FasmRNA and FasLmRNA in AS plaques in group B, but small quantity of them in normal control group(P<0.01). The expression of FasmRNA and FasLmRNA in group D and group E was significantly decreased than group B (dose dependent) (P<0.01). Compared with group A, the expression of FasmRNA did not increase significantly (P>0.05).Conclusion:Resveratrol can inhibit apoptosis of cells in atherosclerotic plaque of atherosclerosis rabbits, have plaque stabilization effects and inhibit the progress of atherosclerosis. It could inhibit the Fas/FasL apoptotic pathway, and depress the expression of caspase-3 mRNA. This effect has dose-effect relationship.