【Animal modeling】-Effect of Shenren Huoxue Granules on TGF-β1/Smad signaling pathway in carbon tetrachloride-induced hepatic fibrosis in rats

  Objective: To observe the effect of Shenren Huoxue Granules on the TGF-β1/Smad signaling pathway of carbon tetrachloride-induced liver fibrosis in rats, and to explore the mechanism of Shenren Huoxue Granules in the treatment of liver fibrosis.

  Methods: 50 male SD rats were randomly divided into normal group, model group and Shenren Huoxue granule low, medium and high dose groups. The normal group was given intraperitoneal injection of normal saline 1 mL/kg, while the model group and Shenren Huoxue granule group were given intraperitoneal injection. 40% carbon tetrachloride 0.2mL/100g intraperitoneal injection, 2 times/week, for 8 consecutive weeks, Shenren Huoxue Granules were given from the 4th week, the low dose group was 1.575g/(kg∙bw) per day, the middle dose The daily dose of 3.15 g/(kg∙bw) in the high-dose group and 6.3 g/(kg∙bw) per day in the high-dose group were given by gavage for 4 consecutive weeks, and the rats were sacrificed at the 8th week. HE staining and Masson staining were used to detect the liver of the rats. The degree of fibrosis; the expression of collagen I, collagen III and TGF-β1 in the rat liver was detected by immunohistochemistry; the expression of TGF-β1, Smad3 and Smad7 in the rat liver was detected by real-time PCR and Western blot.

  Results: Compared with the normal group, the hepatic lobule structure was destroyed in the model group, the fibers were significantly increased, and pseudolobules of different sizes were formed; while the Shenren Huoxue granule groups with different doses significantly improved the degree of liver fibrosis compared with the model group, with Shenren Huoxue granule The high-dose group had the most significant curative effect. ②The expressions of collagen I, collagen III, TGF-β1, and Smad3 in the liver of the model group were significantly higher than those in the normal group (P<0.05), while the expression of Smad7 was significantly decreased (P<0.05). Compared with the model group, the expressions of collagen I, collagen III, TGF-β1 and Smad3 in each dose group of Huoxue Granules were lower than those in the model group (P<0.05), and the expression of Smad7 was higher than that in the model group. ).

  Conclusion: Shenren Huoxue Granules can significantly improve liver fibrosis in rats, and its mechanism may be related to its down-regulation of TGF-β1 and Smad3 expression and up-regulation of Smad7 expression in rat liver tissue, thereby reducing the synthesis of Collagen I and Collagen III.