Effects Of Resveratrol On The Apoptosis And Fas/FasL Apoptotic Pathway In Rabbits With Atherosclerosis

Objectives:The aim of this study was to develop the model of atherosclerotic rabbit,to investigate the effects of resveratrol on the apoptosis and Fas/FasL apoptotic pathway in rabbits with atherosclerosis, And to probe the molecular mechanism for resveratrol of action on anti-atherosclerosis from the level of animal.Methods: 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 RES (4mg/kg.d),D,pathological group treated with mid dosage RES (8mg/ kg.d),E,pathological group treated with high dosage RES (16mg/ kg.d). Rabbits in groups A were fed with normal chow; Rabbits in groups B,C,D and E were fed with high-lipid feeding; at the same time, Rabbits in groups C,D and E were given different dosage resveratrol intervention. all rabbits were sacrificed at the end of the 12th week. Blood glucose and serum lipids levels were measured on the 0,12th weeks. Aortae were analyzed by histopathological examination. Apoptotic index(AI) were detected by Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. The mRNA expression of Fas,FasL and caspase-3 was examined by reverse transcription-polymerase chain reaction(RT-PCR). The analysis of (ANOVA) or non-parametric test of the SSPS software package were used to analyses the data. The value of p<0.05 was statistically considered significant .Results: (1) The blood lipid(TC, TG, LDL-C and HDL-C )of pathological control group is higher than normal control(P<0.01). High,mid,low dose of RES could depress the TG and LDL-C of AS rabbits(P<0.01), the decreasing amplitude in high dose of RES group is maximal. High and mid dose of RES could heighten the HDL-C of AS Rabbits(P<0.05).The differences of blood glucose between 0 week and 12th week were not significant(P>0.05). (2) The atherosclerosis model with rabbits had been successfully established with high fat diet. There were severe pathological lesions in group B. Resveratrol can inhibit the development of atherosclerosis, the pathological of atherosclerosis in group C,D and group E was significantly milder than group B (P<0.05). Resveratrol could greatly diminish the area of plaque and thickness of endomembrane in dose-dependent way.(3) Apoptotic index in group B was significantly increased when compared to group A (P<0.01). Resveratrol can inhibit apoptosis of cells in rabbits with atheroscler- otic plaque, the apoptotic index in group C,D and group E was significantly decreased than group B (P<0.05). There are marked difference between group C,D and group E (P<0.01).(4) There are large quantity of expressing FasmRNA in AS plaques in group B, but small quantity of it in normal control group(P<0.01). The expressing FasmRNA in group D and group E was significantly decreased than group B (P<0.01). Compared with group A, the expression of FasmRNA did not increased significantly (P>0.05).(5) The expression of FasLmRNA greatly increased in group B when comparing to group A (P<0.01). The expression of FasLmRNA in group D and group E was lower (P<0.01) than in group B and higher than in group A (P<0.01). There are not marked significance between group B and group C .(6) The expression of FasLmRNA greatly increased in group B and group C when comparing to group A (P<0.01). Compared with group B and group C, it was significantly reduced in group D and group E(dose dependent) (P<0.01),but still higher than in group A. (P<0.01)(7) The expression of caspase-3mRNA was positively correlated with the expression of FasmRNAï¹™r=0.793, p<0.01).Conclusions: Resveratrol can inhibit apoptosis of cells in rabbits with atherosclerotic plaque, because it could depress the serum TG,LDL-c of AS Rabbits, heighten the HDL-C, inhibit apoptosis and Fas/FasL apoptotic pathway, and depress the expression of caspase-3 mRNA .