氯沙坦抑制球囊损伤后腹主动脉富含半胱氨酸蛋白61、ERK1/2的表达

Effects of losartan on expression of cysteine-rich 61 and ERK1/2 in rat abdominal artery after balloon injury

目的观察球囊损伤后大鼠腹主动脉富含半胱氨酸蛋白61、ERK1/2的表达及氯沙坦对富含半胱氨酸蛋白61、ERK1/2表达的影响,探讨氯沙坦抑制动脉增殖的机制。方法72只雄性Wistar大鼠分为氯沙坦组、球囊损伤组和假手术组。对球囊损伤后不同时间段的大鼠腹主动脉标本采用免疫组织化学、免疫蛋白印记分析检测富含半胱氨酸蛋白61、ERK1/2的表达。结果7 d和14 d球囊损伤组富含半胱氨酸蛋白61、ERK1/2的表达均明显增强,与假手术组比较有显著差异(P<0.01),氯沙坦组与球囊损伤组比较均明显降低。28 d时,3组两两比较没有显著差异(P>0.05)。结论氯沙坦抑制球囊损伤后富含半胱氨酸蛋白61、ERK1/2的表达,提示氯沙坦抑制球囊损伤后内膜增生可能是通过抑制富含半胱氨酸蛋白61发挥作用的,这种抑制作用可能部分是通过ERK1/2信号转导途径介导的。

AIM To observe the effects of losartan on the expressions of cysteine-rich 61 and ERK1/2 in rat abdominal artery injured by balloon. METHODS Seventy-two male Wistar rats were randomized into losartan group, balloon injury group and sham operated group. Balloon injury was conducted in abdominal artery, respectively. Rats were killed at different time points and abdominal artery was collected in time. Intimal hyperplasia was studied by histological morphology method. The expressions of cysteine-rich 61 and ERK1/2 were determined by immunohistochemistry and western-blot method. RESULTS Intimal hyperplasia was present at day 7 after balloon injury, became more obvious at day ld and in progression at day 28. No change was observed in sham operated group. The expressions of cysteine-rich 61 and ERK1/2 increased significantly after balloon injury at day 7 and at day 14. There were significantly different between balloon injury group and sham operated group （P 〈 0.01 ） The expression of cysteine-rich 61 and ERK1/2 decreased significantly after losartan treatment at day 7 and at day 14. There were significantly different between losartan group and balloon injury group （P 〈 0.01 ）. CONCLUSION Cysteine-rich 61 might play an important role in the inhibition of intimal hyperplasia by losartan, which might be mediated through ERK1/2.