1型血管紧张素Ⅱ受体拮抗剂抑制大鼠胰腺纤维化形成

目的探讨1型血管紧张素Ⅱ受体(AT1)拮抗剂洛沙坦对大鼠实验性胰腺纤维化形成的抑制作用。方法胰管内注射2％三硝基苯磺酸(TNBS)诱导大鼠胰腺纤维化模型。于制模后第2天，治疗组给予洛沙坦(10mg／kg体重)灌胃，每日1次，对照组给予等容积的无菌蒸馏水。于制模后3，7，14，21．28d分别处死两组大鼠(每时点各6只)，并留取血清和胰腺组织。通过HE染色和Van Gieson(V-G)染色观察胰腺组织病理学改变和细胞外基质胶原纤维分布。分别应用放射免疫法和酶动力法测定血清透明质酸(HA)和淀粉酶。胰腺组织AT1受体蛋白和mRNA表达分别采用免疫组化和逆转录-聚合酶链式反应(RT-PCR)方法。结果洛沙坦可抑制TNBS诱导的大鼠胰腺纤维化形成，降低胰腺组织炎症细胞浸润、腺泡细胞坏死及纤维化程度，并且能降低血清HA和淀粉酶水平、下调AT1受体基因和蛋白的表达。结论1型血管紧张素Ⅱ受体拮抗剂对TNBS诱导的大鼠胰腺纤维化形成具有抑制作用，表明肾素-血管紧张素系统(RAS)在慢性胰腺炎胰腺纤维化的发生发展过程中起重要的介导调节作用。

Inhibition of pancreatic fibrosis by angiotensin II type I receptor antagonist in rats

Objective To determine whether losartan, an AT1 receptor antagonist, can inhibit pancreatic fibrosis in rats induced by trinitrobenenze sulfonic acid (TNBS). Methods Pancreatic fibrosis was induced in male SD rats by infusion of 2% TNBS into the pancreatic duct. All rats were treated either with losartan (10 mg/kg body weight) by gavage daily in losartan-treated group or with distilled water in the control group. Six rats in each group were sacrificed on day 3, 7, 14, 21 and 28 d after TNBS intraductal infusion. Histological changes of the pancreas were evaluated by HE staining and distribution of extracellular matrix in the pancreatic tissue was assessed by Van Gieson (V-G) staining. Radioimmunoassay was performed to determine the serum level of hyaluronic acid (HA). Expression of AT1 receptor protein and mRNA in pancreatic tissue was detected by immunohistochemical staining and RT-PCR. Results Losartan treatment reduced inflammatory cell infiltration and fibrosis. The serum levels of HA and amylase were decreased and expression of AT 1 receptor down-regulated in the losartan-treated group as compared with the control group. Conclusions Losartan alleviates TNBS-induced pancreatic fibrosis in rats, suggesting that rennin-angiotensin system might be one of the important contributors for formation of pancreatic fibrosis.