摘要
目的研究氧自由基在慢性胰腺炎发病过程中对转化生长因子-β1(TGF-β1)表达的影响及其促胰腺纤维化作用。方法每周2次在大鼠腹腔内注射不同剂量二乙基二硫代氨基甲酸盐(DETC),分别于注射后1.5h,24h,48h,72h,2周,3周,4周,6周将大鼠处死。检测胰腺中超氧歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-PX)活性和丙二醛(MDA)含量以及α-平滑肌肌动蛋白(α-SMA),结蛋白(Desmin)。胶原Ⅰ,Ⅲ(CoⅠ,Ⅲ).转化生长因子β1(TGF-β1),纤维连接蛋白(FN)的表达。结果注入DETC后,胰腺组织内SOD、GSH-PX活性下降,MDA含量升高,提示氧自由基增多,3周后出现较明显纤维化,6周达高峰,与对照组有显著差异(P<0.001)。2周起胰腺内α-SMA,Desmin,TGF-β1呈阳性表达,提示胰腺星状细胞(PSCs)的激活。CoⅠ,CoⅢ,FN的表达2周时弱,4周时强。RT-PCR半定量测定2周时TGF-β1mRNA、FNmRNA水平高于对照组(P<0.001),4周和6周时达高峰。结论氧自由基可能通过激活PSCs刺激TGF-β1的分泌,后者促使了胰腺纤维化的形成。
Objective To clarify the effect of oxygen free radicals on the expression of transforming growth factor-β1 (TCF-β1) and its role in promoting the development of pancreatic fibrosis. Methods Wistar rats were sacrificed at 1. 5 h, 24 h, 48 h, 72 h, 2 w, 3 w, 4 w and 6 w after intraperitoneal administration of diethyldithiocarbamate (DETC) todetect superoxide dismutase(SOD) and glutathione peroxidase(GSH-PX)activities. content of malondialdehyde(MDA) and the expression of α-smooth muscle actin(α-SMA), desmin, collagen Ⅰ , Ⅱ (Co Ⅰ ,Ⅲ). TGF-β1 and fibronectin(FN). Results DETC obviously reduced SOD and GSH-PX activities and increased MDA in pancreatic tissue, suggesting that oxygen free radicals were increased. Fibrosis was observed in the pancreas 3 w after DETC administration and became more serious at 6 w, which was significantly different from control groups(P < 0. 001). From 2 w on, positive expression of α-SMA, desmin, TCP-β1, Co Ⅰ , Ⅲ and FN αSMA was detected in the pancreas, suggesting that pancreatic stellate cells (PSCs) were activated. The expreasion of Co Ⅰ , Ⅲ and FN was weak at 2 w and strong at 4 w. The TGF-β1 mRNA and FN mRNA levels were higher than those of the control group at 2 w by semi-quantitative RT-PCR(P < 0. 001), and reached the peak at 4 w and 6 w. Conclusions Oxygen free radicals might enhance the secretion of TGF-β1, by activating pancreatic PSCs, thus promoting the development of pancreatic fibrosis.
出处
《胰腺病学》
2005年第2期75-78,共4页
Chinese JOurnal of Pancreatology
