分级阻断肾素-血管紧张素系统对大鼠急性胰腺炎的影响及其机制

Action mechanism of the blockade of renin-angiotensin system in grade on acute pancreatitis in rats

目的探讨分级阻断大鼠胰组织肾素-血管紧张素系统对急性胰腺炎的影响及其机制。方法用雨蛙肽诱导大鼠急性胰腺炎模型,观察卡托普利、沙拉新及洛沙坦对大鼠胰湿重比、病理学评分、血浆AMY、MPO、MDA、NO、SOD、TNF-α及Ang-Ⅱ,胰组织MPO、MDA、NO、SOD、TNF-α及Ang-Ⅱ,免疫组织化学ABC法染色胰组织AT1、AT2的影响。结果单用卡托普利、沙拉新、洛沙坦能降低急性胰腺炎血浆AMY、MPO、MDA、NO、TNF-α及Ang-Ⅱ,水平,升高SOD水平;降低胰组织MPO、MDA、NO、TNF-α、Ang-Ⅱ及AT1、AT2水平,升高SOD水平;但联合给药并没有进一步改善急性胰腺炎的所有指标。结论ACE抑制剂、非选择性Ang-Ⅱ受体拮抗剂及特异性AT1阻断剂能改善急性胰腺炎时胰组织损伤程度,但联合应用无协同效果,其可能机制是阻断RAS对胰组织的胰酶过度释放、微循环障碍、氧自由基损伤、炎症介质瀑布样效应有关。

Objective To investigate the action mechanism of the blockage of renin-angiotensin system in grade on acute pancreatitis in rats. Methods The acute pancreatitis in rats was induced with cuelein. The influence of captopril, saralasin and losartan on the levels of AMY, MPO, MDA, NO, SOD, TNF-α and Ang- Ⅱ in plasma, the wet body ratio of pancreas, histological score, the contents of MPO, MDA, NO, SOD, TNF-α and Ang- Ⅱ in the pancreatic tissue, and the expression of AT1 and AT2 in the pancreatic tissue were observed. Results The single use of captopril, saralasin and losartan could decrease the levels of AMY, MPO, MDA, NO, TNF-α and Ang-Ⅱ , and increase the level of SOD in plasma of acute pancreatitis rats; and reduce the wet body ratio, histological score, the levels of MPO, MDA, NO, TNF-α and Ang- Ⅱ ,increase the level of SOD in the pancreatic tissues, and reduce the expression of AT1 and AT2 in the pancreatic tissues of acute pancreatitis rats. However, the combined use of captopril, saralasin and losartan couldn＇ t improve the indexes of acute pancreatitis in rats. Conclusion ACE inhibitor and angiotensin receptor antagonist （nonspecific or specific） alone can reduce the damages to pancreas in rats with acute pancreatitis by blocking pancreatic enzyme release and sepsis mediators,improving pancreatic microcirculation and attenuating the injury of oxygen free radicals, but combined use of them has no synergetic effects on acute pancreatitis.