| Liver fibrosis is a common chronic disease in humans.Without effective intervention,it will further deteriorate into liver cirrhosis and even liver cancer,which seriously threatens human life and health.Due to the complex and changeable mechanism of liver fibrosis,there is no effective treatment drug in clinical practice.Traditional Chinese medicine has many advantages,such as many active ingredients,many targets and small side effects.Therefore,it shows great application prospects in the treatment of liver fibrosis.Panax notoginseng is a precious traditional Chinese medicinal material in Chinese,which can effectively reduce the degree of liver fibrosis,but its mechanism of action needs to be further studied.Based on this,this subject will study the anti-liver fibrosis activity and mechanism of Panax notoginseng from the molecular level of signaling pathways and the level of intestinal bacterial communities respectively.The main contents are as follows:1.Study on the pharmacological activity of Panax notoginseng against liver fibrosis.Male SD rats were used as experimental animals,and a rat liver fibrosis model was constructed using the method of bovine serum albumin immune induction.The anti-liver fibrosis of Panax notoginseng was investigated from the aspects of organ index,histopathological section,serum marker detection,and ultrasound imaging.The experimental rats were divided into normal control group,liver fibrosis model group and Panax notoginseng administration group.The results of organ index and liver histopathological section showed that compared with the liver fibrosis model group,the liver index and spleen index of rats in the Panax notoginseng administration group were reduced by 10.42% and 19.25% respectively,at the same time,the liver cell injury and collagen fiber proliferation in the liver tissue were improved,and the structure tended to be normal.Serum marker detection results showed that Panax notoginseng could significantly reduce the expression levels of alanine aminotransferase,aspartate aminotransferase and hyaluronic acid in rats serum,indicating that Panax notoginseng could promote the recovery of rat liver function,and reduce the degree of liver fibrosis in rats.Compared with the liver fibrosis model group,the imaging test results showed that the two-dimensional mean value of the liver of the rats in the Panax notoginseng administration group increased from(19.26±2.87)d B to(24.24±3.98)d B,and the liver stiffness value decreased from(25.63±4.48)Kpa to(16.81±5.49)Kpa,it indicated that the intervention of Panax notoginseng could significantly improve the echo of liver parenchyma and liver stiffness in rats,and had good pharmacological activity against liver fibrosis.2.Study on the molecular mechanism of Panax notoginseng against liver fibrosis.Aiming at the main pathogenesis of liver fibrosis,the anti-liver fibrosis mechanism of Panax notoginseng was studied at the molecular level of inflammation,hepatic stellate cell activation,extracellular matrix deposition and related regulatory signaling pathways.Experimental results of blood biochemical indicators showed that Panax notoginseng could effectively reduce the serum levels of tumor necrosis factor-α and interleukin-1 in rats with liver fibrosis,which helps to inhibit liver inflammation and slows the development of liver fibrosis.Further research results showed that compared with the liver fibrosis model group,the expression levels of the hepatic stellate cell activation marker α-smooth muscle actin(α-SMA)and the extra matrix deposition markers hydroxyproline(Hyp)and type I collagen(Collagen I)in the liver tissue of the rats in the Panax notoginseng administration group were significantly reduced by 21.70%,51.75% and 20.45% respectively,at the same time,the expression of Rho A and ROCK1 protein in the Panax notoginseng administration group were also significantly reduced.The results showed that Panax notoginseng could inhibit the activation of hepatic stellate cells and reduce collagen deposition by down-regulating the Rho A/ROCK1 signaling pathway,thereby reversing liver fibrosis.3.Diversity analysis of intestinal flora of Panax notoginseng against liver fibrosis.Studies have shown that the composition of the intestinal bacterial community is closely related to liver fibrosis.Therefore,in this chapter,we used the Illumina Miseq platform to perform high-throughput sequencing on the 16 S r DNA of intestinal bacteria to analyze the effect of Panax notoginseng on the intestinal flora of rats with liver fibrosis.The experimental results showed that the three samples of the normal control group,the liver fibrosis model group,and the Panax notoginseng administration group obtained a total of 834 species at the level of the operational taxonomic units.The results of Alpha diversity and Beta diversity analysis showed that compared with the liver fibrosis model group,the diversity and composition of the intestinal bacterial community of rats in the Panax notoginseng administration group had significant changes,it showed Panax notoginseng had a certain regulatory effect on the intestinal flora of liver fibrosis rats.At the level of genus taxonomy,the analysis of species composition and species differences showed that the intervention of Panax notoginseng significantly promoted the increase of the beneficial bacteria Lactobacillus in the intestines of rats,and inhibited the proliferation of harmful bacteria unclassified＿f＿Prevotellaceae,and their relative abundance was respectively2.123 times and 0.138 times that of the liver fibrosis model group.The relationship between intestinal microbes and liver fibrosis was further analyzed through environmental factor correlation,and the results showed that Panax notoginseng could affect the expression levels of TNF-α,IL-1 in rat serum and Hyp,α-SMA,Collagen I and Rho A/ROCK1 in liver tissues,it further promoted the increase of beneficial bacteria Lactobacillus and norank＿f＿Lachnospiraceae,and inhibited the proliferation of harmful bacteria such as Prevotellaceae＿Ga6A1＿group in the intestines of rats with liver fibrosis,reshaped the structure of the intestinal flora of rats,thereby producing prevention and treatment effects. |
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