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目的观察大黄丹参水煎剂抗胰腺纤维化的可能作用机制。方法 50只雄性Wistar大鼠随机分为正常组、模型组和大黄丹参水煎剂低、中、高剂量组,每组10只。腹腔注射二乙基二硫代氨基甲酸钠(DDC)6周建立胰腺纤维化模型。大黄丹参水煎剂低、中、高剂量组在造模同时分别给予大黄丹参水煎剂0.137、0.274、0.548 g/(kg·d)灌胃,正常组和模型组给予等量生理盐水灌胃,连续给药6周。免疫组化检测胰腺α-平滑肌肌动蛋白(α-SMA)表达,RT-PCR检测胰腺大鼠转化生长因子β1(TGF-β1)mRNA、血小板衍生生长因子BB(PDGF-BB)mRNA表达,免疫印迹法检测TGF-β1蛋白、PDGF-BB蛋白表达。结果正常组α-SMA低表达,模型组α-SMA高表达,大黄丹参水煎液各剂量组α-SMA均有不同程度的减弱。模型组TGF-β1、PDGF-BB蛋白B mRNA表达较正常组上调(P<0.05或P<0.01);与模型组比较,大黄丹参中、高剂量组TGF-β1蛋白及mRNA表达下调,大黄丹参高剂量组PDGF-BB蛋白及mRNA下调(P<0.05或P<0.01)。与大黄丹参中剂量组比较,大黄丹参高剂量组TGF-β1蛋白下降显著(P<0.05)。结论“下调TGF-β1及PDGF-BB及其mRNA表达—抑制α-SMA表达—抑制PSC活化—减少ECM合成—改善ECM沉积”可能是大黄丹参抗胰腺纤维化的作用机制之一。
Objective To observe the possible mechanism of anti-pancreatic fibrosis of Radix et Rhizoma Rhei decoction. Methods Fifty male Wistar rats were randomly divided into normal group, model group and Rhubarb salvia miltiorrhiza decoction low, medium and high dose group, 10 rats in each group. The model of pancreatic fibrosis was established by intraperitoneal injection of sodium diethyldithiocarbamate (DDC) for 6 weeks. Rhubarb Danshen decoction low, medium and high dose group were given Rhubarb Danshen decoction 0.137,0.274,0.548 g / (kg · d) gavage at the same time, the normal group and model group given the same amount of saline gavage , Continuous administration for 6 weeks. The expression of α-smooth muscle actin (α-SMA) in pancreas was detected by immunohistochemistry. The expression of TGF-β1 mRNA and PDGF-BB mRNA was detected by RT-PCR. The expression of TGF-β1 and PDGF-BB were detected by Western blot. Results The expression of α-SMA was low in normal group and α-SMA in model group. Α-SMA in each dose group of Rhubarb Danshen decoction decreased to some extent. Compared with the model group, the expression of TGF-β1 and PDGF-BB protein B mRNA and protein in the model group were significantly up-regulated (P <0.05 or P <0.01) High-dose group PDGF-BB protein and mRNA downregulation (P <0.05 or P <0.01). Compared with Danshen Danshen middle-dose group, TGF-β1 protein in Rhubarb Danshen high-dose group decreased significantly (P <0.05). Conclusion “Down-regulating the expression of TGF-β1 and PDGF-BB and its mRNA - inhibiting the expression of α-SMA - inhibiting PSC activation - decreasing ECM synthesis - improving ECM deposition” may be one of the mechanisms of anti-pancreatic fibrosis in Radix Salviae miltiorrhizae.