Therapeutic Effect Of Notoginsenoside R1 On CCL4-Induced Liver Fibrosis In Rats

Background: Research background and purpose: In recent years,the number of liver cancer patients has increased day by day,and liver fibrosis is the main liver background factor for its occurrence and development.Liver fibrosis is a dynamic and reversible process with the ability to repair itself.The reversibility of liver fibrosis provides an effective early window for treatment.However,there is currently no ideal anti-fibrotic drug in clinic.Various types of cells and cytokines are involved in the pathogenesis and progression of liver fibrosis,cirrhosis,and portal hypertension(PHT).Among them,hepatic stellate cells(HSCs)are the most important effector cells.Under the action of liver damage factors,the resting HSCs are transformed into myofibroblast-like phenotypes.The activated HSCs have the following characteristics:proliferation,migration to the injury site,and the production of a large amount of extracellular matrix(ECM)Protein,secretion of pro-fibrosis factor,etc.Too much ECM is deposited under the endothelium of liver sinusoidal endothelial cells(LSECs),forming a continuous basement membrane,called "liver sinusoidal endothelial cells(LSECs)".LSECs produce ECM proteins such as fibronectin(FN)and secrete pro-fibrotic cytokines such as transforming growth factor β1(TGF-β1).The TGF-β1pathway is one of the most important signaling pathways in the process of liver fibrosis,and TGF-β1 is the strongest cytokine in the liver to promote fibrosis,which can promote the synthesis of multiple ECM proteins by HSCs and LSECs.Previous studies found that Panax notoginseng saponins have a certain protective effect on immune liver injury mice.Notoginsenoside R1,as the main component of notoginsenoside,plays an important role in the treatment of lung and kidney fibrosis and inflammation.But the specific active ingredients are not clear.This study initially explored the therapeutic effect of panax notoginsenoside R1 on rat liver fibrosis induced by carbon tetrachloride.Method: Male SD rats were randomly divided into three groups: control group,liver fibrosis group and notoginsenoside R1 treatment group.Rats in the control group were intraperitoneally injected with olive oil twice a week;rats in the cirrhosis group were intraperitoneally injected with CCl4 twice a week to build a rat model of liver fibrosis;rats in the Notoginsenoside R1 treatment group were injected with CCl4 intraperitoneally for 8 weeks.Rats were given subcutaneous injection of panax notoginseng saponin R1.The liver specimens of rats in each group were collected,and hematoxylin-eosin(HE)staining was used for liver tissue examination.Masson staining was used to observe the degree of ECM deposition in the liver.RT-qPCR was used to detect liver fibrosis.Indicators such as α-smooth muscle actin(α-smooth muscle actin,α-SMA),collagen Ⅰ(Collagen-Ⅰ)and important cytokine promoting growth factor transforming growth factor β1(transforming growth factor β1,TGF-β1).Conclusion: 1.The liver histopathology showed that notoginsenoside R1 can significantly reduce the degree of fibrous hyperplasia compared with the model group.2.Compared with the model group,the expression levels of type I collagen,α-smooth muscle agonist protein and transforming growth factor β1 in t Notoginsenoside R1 group were significantly reduced(P <0.05).Notoginsenoside R1 has a certain therapeutic effect on CCL4-induced liver fibrosis model rats.