The Influence Of Decorin On Expression Of TGF-β1, α-SMA In CCl₄ Induced Mice With Liver Fibrosis

Objective: There are no effective drugs for the therapy of hepatic fibrosis currently. In this study, we constructed the hepatic fibrosis mouse model by applying with carbon tetrachloride(CCl4) to explore the influence of decorin(DC) on the expression of proteins TGF-β1, α-SMA in liver tissue of mouse with liver fibrosis, and to explore its action mechanism for treating liver fibrosis, aiming to provide drug candidates for clinical treatment of hepatic fibrosis.Methods: A total of 40 Balb/c mice were collected in this research, among which 15 were randomly assigned into the blank control group, and the remaining 25 mice were given CCl4 for constructing the model. In order to establish a mouse model of liver fibrosis, mixture of CCl4 and olive oil was given by fasting intraperitoneal injection, use dosage of CCl4 being 1ml/kg, and the volume ratio of CCl4 and olive oil being 1: 1, administered once every two days. Blank control group received olive oil. 3 weeks later, we randomly selected 5 mice from the control group and CCl4 processed mice, respectively, then observed their changes in liver surface; basing on histopathological examination of liver, we tested whether liver fibrosis mode is successfully established. The remaining 20 CCl4 processed mice were randomly divided into the model group and the intervention group(DC given as 250μg/kg). After 2 weeks, the mice were killed. The liver pathological section was stained using HE and Masson methods to evaluate the statements of liver damage and fibrosis, then expression of the proteins TGF-β1, α-SMA in liver were detected by immunohistochemistry(IHC) methods.Results: The HE and Masson staining methods were applied on the liver tissue after DC was processed for 2 weeks in the HF mouse model. In the study, we found that DC could ease the intensity of HF in CCL4 induced HF mouse model. That is the decreasement in liver cell alteration and necrosis, in inflammatory cell infiltration and in collagen fibers deposits, and further more, fibrous septa became narrower. IHC showed that: 1. Expression of TGF-β1 protein in normal liver control group was significantly lower to both the model group and the intervention group, the difference was statistically significant(P<0.05). 2. Expression of α-SMA protein in normal liver control group was significantly lower to both the model group and the intervention group, the difference was statistically significant(P<0.05). 3. Expression of TGF-β1 protein from the liver of mouse in the intervention group was significantly lower compared to the model group and the difference was statistically significant(P<0.01). 4. Expression ofα-SMA protein from the liver of mouse in the intervention group was significantly lower compared to the model group and the difference was statistically significant(P<0.01).Conclusion: DC reduce activation of hepatic stellate cells(HSC) probably by decreasing the expression level of TGF-β1 in the Balb/c mouse liver tissue, then reduce synthesis of the extracellular matrix(ECM), and ultimately exert the therapeutic action, even reverse the HF.