白藜三醇抑制大鼠血管平滑肌细胞增殖的作用机制

目的 探讨植物雌激素白藜三醇（RV）对大鼠血管平滑肌细胞增殖的调控及可能机制.方法 用植块贴壁法体外培养大鼠血管平滑肌细胞,使用Western blotting检测各组雌激素受体α（ERα）、雌激素受体β（ERβ）、P38、P-P38、C-myc蛋白的表达水平.实验分为6组（每组n=6）：正常对照组（NC组）,含10% 胎牛血清（FBS）的DMEM; RV干预组（RV组）,50 μmol/L RV干预24 h; 血管紧张素Ⅱ组（AngⅡ组）,1 μmol/L AngⅡ干预12 h;RV＋ AngⅡ组,1 μmol/L AngⅡ干预12 h,然后加入50 μmol/L RV干预24 h;RV＋ICI182780组,1 μmol/L ICI182780干预2 h,然后加入50 μmol/L RV干预24 h;RV＋ICI182780＋AngⅡ组,1 μmol/L ICI182780干预2 h,然后加入1 μmol/L AngⅡ干预12 h,最后加入50 μmol/L RV干预24 h.结果 各组P38蛋白表达差异无统计学意义（P＞0.05）;ERα、ERβ蛋白的表达：RV组ERα、ERβ蛋白的表达水平较正常对照组增高（P＜0.01）,而RV＋ICI182780组与RV组比较表达降低（P＜0.01）;C-myc蛋白的表达：RV组与NC组比较表达降低（P＜0.01）,AngⅡ组与NC组比较表达增高（P＜0.01）,AngⅡ组与RV组比较表达增高（P＜0.01）,RV＋AngⅡ组与RV组比较表达增高（P＜0.01）,RV＋ICI182780＋AngⅡ组与RV＋AngⅡ组比较表达降低（P＜0.05）;P-P38蛋白的表达：RV组与NC组比较表达降低（P＜0.01）,AngⅡ组与NC组比较表达增高（P＜0.01）,AngⅡ组与RV组比较表达增高（P＜0.01）,RV＋AngⅡ组与RV组比较表达增高（P＜0.01）,RV＋ICI182780＋AngⅡ组与RV＋AngⅡ组比较表达降低（P＜0.01）.结论 白藜三醇可以抑制C-myc的表达,抑制P38的磷酸化,此作用可被ICI182780阻断,说明白藜三醇可能是通过ER进而抑制C-myc的表达和P38的磷酸化发挥抗平滑肌细胞增殖的作用.

The mechanisms of resveratrol inhibiting the proliferation of vascular smooth muscle cells in rats

Objective To investigate the regulation of the phytoestrogen resveratrol （RV） on the proliferation of vascular smooth muscle cells in rats and the possible underlying mechanism. Methods Rat vascular smooth muscle cells were cultured using adherent explant method in vitro, and the protein expressions of estrogen receptor α （ERa） , ERI3, P38, P -P38 and C -myc were detected by Western blotting. The rats were divided into six groups （n =6 each） ： normal control group （NC group）, which contained DMEM with 10% of fetal bovine serum （FBS） ; RV intervention group （RV group）, which underwent 50 μmol/L RV intervene for 24 h; angiotensin U group （Ang 1/ group ）, which underwent intervention with 1 μmol/L Ang II for 12 h; RV ＋ Ang II group, which underwent intervention with 1 μmol/L Ang II for 12 h, followed by the addition of 50 μmol/L RV for subsequent intervention for 24 h; RV ＋ ICI182780 group, which underwent intervention with 1 μmol/L ICI182780 for 2 h, followed by the addition of 50 μmol/ L for subsequent intervention for 24 h; RV ＋ ICI182780 ＋ Ang II group, which underwent intervention with 1 μmol/L ICI182780 for 2 h, followed by the addition of I ixmoL/L Ang II for subsequent intervention for 12 h and further addition of 50 txmol/L RV for intervention for 24 h. Results The differences in the expression levels of P38 among the groups had no statistical significance （ P 〉 0.05 ）. The protein expression levels of ERa and ERI3 ：The protein expression levels of ERa and ER3 were increased in RV group compared with NC group （P 〈 0.01 ）. while those in RV ＋ Ici182780 group were decreased as compared to RV group（P 〈 0.01 ） ;The protein expression levels of C - myc：The protein expression levels of C - myc were decreased in RV group compared with NC group （ P 〈 0.01 ）. Those in Ang H group were in- creased as compared to NC group（P 〈 0.01 ）. Those in Ang II group were increased as compared to RV group（P 〈 0.01）. Those in RV ＋Ang 1I group were increased as compared to RV group（P 〈0.01 ）. Those in RV ＋ Ici182780 ＋ Ang II groupwere decreased as compared to RV ＋ Ang I1 group（ P 〈 0.05 ） ;The protein expression levels of P- P38 ：The protein expression levels of P - P38 were decreased in RV group compared with NC group（ P 〈 0.01 ）. Those in Ang I/ group were increased as compared to NC group （ P 〈 0.01 ）. Those in Ang H group were decreased as compared to RV group（P 〈0.01 ）. Those in RV ＋ Ang H group were increased as compared to RV group （ P 〈 0.01 ）. Those in RV ＋ 1ci182780 ＋ Ang ]I were decreased as compared to RV ＋ Ang II group（ P 〈 0.01 ）. Conclusion RV could inhibit the ex- pression of C -myc and the phosphorylation of P38, but this action could be blocked by ICI182780, which suggests that the anti - proliferative effect of RV on vascular muscle cells by inhibiting the expression of C - myc and the phosphorylation of P38 via the ER pathway.