目的:探讨和解利湿方对酒精性慢性胰腺炎(ACP)大鼠胰腺纤维化及TGF-β/Smad/ERK信号通路的影响。方法:Lieber-DeCarli酒精流质饮食联合尾静脉注射脂多糖(LPS)制备大鼠ACP模型。以不同浓度(2.170、1.085、0.543g/mL)的和解利湿方治疗4周后,采用HE和天狼猩红染色观察胰组织病理变化,碱水解法检测胰腺组织羟脯氨酸(HYP)含量变化,Western Blot法检测α-SMA、FN及TGF-β/Smad/ERK信号通路蛋白的表达。结果:与模型组比较,高剂量的和解利湿方显著减轻大鼠ACP纤维化病变;减少HPY含量;减少α-SMA,FN,TGF-β1,Smad2、3,P-Smad 2、3,ERK1以及P-ERK1/2的表达。结论:高剂量的和解利湿方对ACP胰腺纤维化可能有一定的治疗作用,其机制可能与调节胰腺组织TGF-β/Smad/ERK信号通路蛋白的表达和抑制其通路蛋白活化有关。
Objective: To investigate the effects of Hejie Lishi Formula on pancreatic fibrosis through TGF-β/Smad/ERK pathway in rat alcohol chronic pancreatitis (ACP). Methods: The rat ACP model was established by feeding Lieber-DeCarli Liquid diet containing ethanol and injection of lipopolysaccharide (LPS) into caudal vein. The rats were treated by different concentrations (2.170, 1.085, 0.543g/mL) of Hejie Lishi Formula. After 4 weeks of treatment, the pathological changes of pancreatic tissue were observed by HE and picrosirius red stainings, the levels of hydroxyproline contents in pancreatic tissue by alkaline hydrolysis, and the levels of a-SMA, FN, TGF-131, Smad2, 3, P- Smad2, 3, ERK1 and P-ERK1/2 expressions in pancreatic tissue were detected by Western Blot. Results: Compared to control group, high-dose of Hejie Lishi Formula not only alleviated fibrosis and reduced hydroxyproline contents, but also reduced the levels of a-SMA, FN, TGF-β1, Smad2, 3, P-Smad2, 3, ERK1 and P-ERK1/2 expressions in pancreatic tissue of ACP rats. Conclusion: High-dose of Hejie Lishi Formula may prevent against the fibrosis of pancreatic tissue, through regulating protein expressions and activations of TGF-β/Smad/ERK pathway in ACP rats.