胰腺星状细胞在大鼠胰腺纤维化形成中的作用  

Roles of pancreatic stellate cells in the pathogenesis of pancreatic fibrosis in rats

作　　者：王兴鹏[1] 张汝玲[1] 龚自华[1] 吴恺[1] 

机构地区：[1]上海市第一人民医院

出　　处：《中华消化杂志》2003年第8期466-469,共4页Chinese Journal of Digestion

基　　金：上海市科技发展基金 (0 14 1190 65 )

摘　　要：目的　动态观察三硝基苯磺酸 (TNBS)胰管内注射诱导大鼠胰腺纤维化过程中胰腺星状细胞 (PSC)的活化情况 ,并研究PSC相关介质转化生长因子 β1(TGF β1)、基质金属蛋白酶 2 (MMP 2 )和Ⅰ型胶原蛋白表达 ,探讨PSC在胰腺纤维化形成过程中的作用。方法　通过胰管内注射含 2 %TNBS的乙醇磷酸盐缓冲液诱导大鼠胰腺纤维化模型 ,并分别于术后 72h和 3、4、5、6、7周处死大鼠 ,留取胰腺组织。胰腺组织切片经HE染色 ,光镜下观察病理学变化。分别用免疫组化、RT PCR、Westernblot检测胰腺组织α 平滑肌肌动蛋白 (α SMA)、TGF β1、MMP 2mRNA和Ⅰ型胶原蛋白表达 ;电镜观察不同时点胰腺组织超微结构变化。结果　 2 %TNBS胰管内注射后早期主要以胰腺组织炎症、水肿、坏死为主 ,3周后则以纤维组织增生、腺泡萎缩、胶原沉积等纤维化表现为主 ,以第 4周为甚。第 3周时α SMA表达量较少 ,第 4周时则显著增多 ,而后又渐减。第 3周时胰腺组织TGF β1蛋白表达显著增加 ,4周时达峰值。正常胰腺组织仅有极微量MMP 2mRNA表达 ,而制模早期胰腺组织即有MMP 2mRNA表达显著增加 ,随时间延长其表达量呈波动性变化 ,但仍明显高于正常。正常胰腺组织间质有少量Ⅰ型胶原表达 ,而在胰腺纤维化区域则可见大量Ⅰ型胶原沉积。Objective To observe the activation of pancreatic stellate cells (PSC) during the formation of pancreatic fibrosis induced by the pancreatic injection of trinitrobenzene sulfonic acid (TNBS). Meanwhile, the effects of PSC-related factors, such as transforming growth factor β 1 (TGF-β 1), collagen Ⅰ and MMP-2 on the pathogenesis of pancreatic fibrosis in rats were also evaluated. Methods Pancreatic fibrosis model in rats was induced by the injection of 2% TNBS in ethanolate-phosphate buffer solution into the pancreatic duct. The rats were sacrificed and the pancreata were removed at the 72nd hour, 3rd week, 4th week, 5th week, 6th week and 7th week after the operation respectively. Expressions of α-smooth muscle actin (α-SMA), transforming growth factor β 1 (TGF-β 1), collagen Ⅰ and MMP-2 were determined by either immunohistochemistry or RT-PCR, or Western blot respectively. The ultrastructure of pancreas was studied by electron microscope at different time points. Results The inflammation, swelling and necrosis were the major pathological changes of the pancreas at the early stage after the injection of 2% TNBS. Subsequently, the fibrotic manifestations such as proliferation of the fibrosis, atrophy of vesicles, deposition of collagen because prominent at the 3rd week after the operation, which peaked at 4th week. The expression of TGF-β 1 was increased significantly at the 3rd week after the operation and reached maximum at the 4th week. The expression of α-SMA, which indicated the activation of PSC, could be detected at the 3rd week and also reached the peak value at the 4th week. After wards, it was decreased gradually. During the first 72 hours, the expression of MMP-2 mRNA was increased significantly and then was fluctuated but still higher than that in normal rats. The deposition of type Ⅰ collagen was increased in the areas of fibrotic tissues. Conclusions PSC might involve in the courses of the development and progression of TNBS induced pancreatic fibrosis in rats. This action wa

关 键 词：胰腺星状细胞 大鼠 胰腺纤维化形成 三硝基苯磺酸 胰腺纤维化 慢性胰腺炎 

分 类 号：R576[医药卫生—消化系统]