氯沙坦拮抗急性胰腺炎胰腺纤维化启动的研究(1)
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【中图分类号】R969.4【文献标识码】A【文章编号】1005-2720(2009)08-0281-04
【摘要】目的:应用免疫组化、RT-PCR等测定方法从组织细胞、基因等水平探讨AT-Ⅱ受体拮抗剂对急性胰腺炎大鼠纤维化启动的作用及意义。方法:采用SHOP法诱导急性胰腺炎大鼠模型,治疗组大鼠给予氯沙坦灌胃,时间从术前3d始,至时间点止,对照组给予生理盐水灌胃。分别于72h、120h处死大鼠,取完整胰腺组织用免疫组化方法检测Ⅰ型胶原和α-SMA的表达,再以逆转录聚合酶链反应(RT-PCR)检测TGF-β1 mRNA、Coll-Ⅰ mRNA的表达情况,并根据结果统计治疗组和对照组差异。结果:光镜下比较可见两组均出现典型急性胰腺炎组织表现,但两组对比无明显可见差异。免疫组化显示对照组和治疗组α-SMA染色无比较差异,治疗组较对照组染色无明显减轻;Coll-Ⅰ分布范围基本同α-SMA,经统计学处理亦无明显差异出现。RT-PCR结果显示,TGF-β1、Coll-Ⅰ的mRNA表达均较正常组明显增强,可见干预组TGF-β mRNA表达量较对照组有所减少,而Coll-Ⅰ的mRNA在72h组变化不明显,而于120h组则略有下降。结论:RAS系统在急性胰腺炎中活性明显增强,和胰腺纤维化之间关系紧密。AT-Ⅱ受体抑制剂能够抑制胰腺内TGF-β mRNA的表达,并最终在一定成度上影响ECM生成。RAS系统是影响胰腺纤维间质组织生成的所有因素中的一个重要部分,单纯抑制RAS系统虽然不能完全阻止胰腺纤维化的产生,但在某种程度上能够延缓纤维化的进展。
【关键词】急性胰腺炎;胰腺纤维化;Ⅰ型胶原;α-平滑肌激动蛋白;转化生长因子-β1
Study of losarton in suppressing pancreatic fibrosis.Wu Fugang1,Zhang Zhigao2,Sun Ziqin2,et al.(1Zhangying hospital of Yuncheng county,Shandong 274700 China;2General hospital of Jinan military reagion of PLA)
【Abstract】Objective:The study is to investigate the effect of losarton,a AT-Ⅱ receptor antagonist,on the start of pancreatic fibrosis in the early time of acute pancretitis by determining the expression of transforming growth factor-β1(TGF-β1)and Collagen Ⅰ messenger RNA and deposition of Collagen-Ⅰ、α-smooth muscle actin(α-SMA)in acute pancreatitis.Methods:Acute pancreatitis was induced in rats by SHOP for 72h and 120h.Treatment group animals are gavaged with losarton 3 days before the induction of pancreatitis,and control animals only with saline.Entire pancreas is harvested in the timepoint of 72h and 120h.Imunohistochemistry was performed with collagen-Ⅰ and α-smooth muscle actin antibodies.Messenger RNA of transforming growth factor-β1(TGF-β1)and Collagen-Ⅰ was detected by reverse transcriptive polymerase chain reaction(RT-PCR) ......
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