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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。
Objective To investigate the inhibitory effect of losartan, an antagonist of type 1 angiotensin Ⅱ receptor (AT1), on experimental pancreatic fibrosis in rats. Methods Pancreas fibrosis model was induced by intraperitoneal injection of 2% trinitrobenzene sulfonic acid (TNBS). On the second day after modeling, losartan (10mg / kg body weight) was given intragastrically in the treatment group once a day, and the control group was given equal volume of sterile distilled water. At 3, 7, 14, 21 and 28 days after model establishment, two groups of rats (6 in each group) were killed, and serum and pancreatic tissue were collected. Pancreatic histopathological changes and extracellular matrix collagen distribution were observed by HE staining and Van Gieson (V G) staining. Serum hyaluronic acid (HA) and amylase were determined by radioimmunoassay and enzyme kinetic assay respectively. Pancreatic tissue AT1 receptor protein and mRNA expression were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT PCR) method. Losartan inhibited TNBS-induced pancreatic fibrosis in rats, decreased pancreatic inflammatory cell infiltration, necrosis of acinar cells and fibrosis, decreased serum levels of HA and amylase, decreased AT1 receptor gene and protein expression. Conclusion Angiotensin Ⅱ type 1 receptor antagonist has an inhibitory effect on TNBS-induced pancreatic fibrosis in rats, indicating that renin-angiotensin system (RAS) plays an important role in the development of pancreatic fibrosis in chronic pancreatitis Mediate regulation.