Experimental Study Of Baogan Decoction On Intervention Of Chronic Chemical Liver Injury

Purpose:Through this experiment,the protective effect of Baogan Decoction on the liver of mice with chronic chemical liver injury induced by carbon tetrachloride（CCl₄）was studied,and the mechanism of baogan decoction was preliminarily revealed.Material and method:Male SPF level Kunming mice were randomly divided into 6groups according to body weight,namely,normal group,model group,Hugan Tablet group,high-dose group of Baogan Decoction group,medium-dose group of Baogan Decoction group and low-dose group of Baogan Decoction group,14 mice in each group,a total of 84 mice.In addition to the normal group,the rest groups were intraperitoneally injected with 0.5%CCl₄solution(0.1mL·10g^-1)prepared with vegetable oil at the first,the third,the tenth,the sixteenth,the twenty-second,the twenty-fifth and the twenty-eighth of the experimental cycle,respectively.Gastric gavage was started on the 10th day after the modeling,in which the normal group and the model group were given distilled water(0.1mL·10g^-1),Hugan Table group（0.5g·kg-1）,high-dose Baogan Decoction group(32g·kg^-1),medium-dose Baogan Decoction group(16g·kg^-1),and low-dose Baogan Decoction group(8g·kg^-1)were given corresponding drugs once a day.On the 30th day of the experiment,two hours after the administration,samples were taken and indicators were detected.Liver general conditions and pathological changes were observed,and liver index was calculated.the activity of ALT,AST,MDA and SOD were detected by biochemical methods,LPS and CD14 protein activities were detected by ELISA,and Raf-1,ERK-1 and PPAR-amRNA expressions were detected by QPCR.The SPSS16.0 software was used to calculate the experimental data.Result:1 Effect on pharmacodynamics of mice with chronic chemical liver injury1.1 General liver condition of mice with chronic chemical liver injuryMacroscopic observation showed that the liver surface of mice in the model group was not smooth,with uneven nodules,blunt edges and different thickness.1.2 Liver histopathological changes in mice with chronic chemical liver injuryOptical microscope,the model group mice liver central vein and hepatic cell morphology and structure deformation,the arrangement of liver cell level disorders,liver cell swelling,boundary is not clear,the nucleus,nucleolus disappeared,and see many focal necrosis,building success.1.3 Effects of serum ALT,AST and AST/ALT in mice with chronic chemical liver injury1.3.1 Effect on serum ALT in mice:the serum ALT level in the model group was significantly higher than that in the normal group（P<0.05）.Compared with the model group,Baogan Decoction was significantly reduced in each group（P<0.05）.The difference between the two groups was significant（P<0.05）.1.3.2 Effects on serum AST in mice:the serum AST in the model group was significantly higher than that in the normal group（P<0.05）.The medium dose group and model group of Baogan Decoction group was significantly reduced（P<0.05）.The difference between the two groups was significant（P<0.05）.1.3.3 Effects of AST/ALT ratio on mice:the AST/ALT value of mice in the model group was slightly increased,but there was no statistical difference（P>0.05）.Compared with the model group,the dose of Baogan Decoction in each group increased significantly,and the difference was statistically significant（P<0.05）.2 Effect on the mechanism of chronic chemical liver injury in mice2.1 Effects on serum MDA and SOD in mice with chronic chemical liver injury2.1.1 Effects on serum MDA in mice:compared with the normal group,the serum MDA value of the model group was significantly increased（P<0.05）.Compared with the model group,Baogan Decoction was significantly reduced in the medium and low dose groups（P<0.05）.Comparison between groups showed that the high-dose group of Baogan Decoction wa significantly higher than the medium-dose group（P<0.05）,with no significant difference in the rest.2.1.2 Effect on serum SOD in mice:compared with the normal group,the serum SOD value of mice in the model group was significantly decreased（P<0.05）.Compared with the model group,SOD values in the high,medium and low dose groups of Baogan Decoction were significantly increased（P<0.05）.Comparison between groups with different doses of Baogan Decoction showed that medium and low doses of Baogan Decoction were significantly higher than those with high doses of Baogan Decoction（P<0.05）.There was no significant difference between the medium and low dose groups（P>0.05）.2.2Effect of Baogan Decoction group on LPS and CD14 in liver tissue of mice with chronic chemical liver injury2.2.1 Effect on LPS of mouse liver tissue:Compared with the normal group,the LPS of the model group was significantly increased（P<0.05）.Compared with the model group,the drug delivery groups were significantly reduced（P<0.05）.The difference between the two groups was statistically significant（P<0.05）.The low dose group was significantly higher than the high and medium dose group（P<0.05）.2.2.2 Effect on CD14 in mouse liver tissue:Compared with the normal group,the liver CD14value in the model group was significantly increased（P<0.05）.Compared with the model group,the drug delivery groups were significantly reduced（P<0.05）.The difference between the two groups was statistically significant（P<0.05）.The low dose group was significantly higher than the medium dose group（P<0.05）.2.3 Effect of Baogan Decoction group on the Raf-1,ERK-1 and PPAR-amRNA in liver tissue of mice with chronic chemical liver injury2.3.1 Effect on Raf-1 mRNA in mouse liver tissue:compared with the normal group,the expression of Raf-1 mRNA in mouse liver was significantly increased in the model group,and the difference was statistically significant（P<0.05）.Compared with the model group,the drug delivery groups were significantly reduced（P<0.05）.Compared between groups,the high-dose group of Baogan Decoction was significantly lower than the medium-dose and low-dose group（P<0.05）.There was no significant difference between the medium and low dose groups（P>0.05）.2.3.2 Effect on ERK-1 mRNA in liver tissues of mice:ERK-1 mRNA expression in liver tissue of model group was significantly higher than that of normal group（P<0.05）.Compared with the model group,the drug delivery groups were significantly reduced（P<0.05）.Compared between groups,the low dose group of Baogan Decoction was significantly higher than the high and medium dose group（P<0.05）.2.3.3 Effect on PPAR-amRNA expression in liver tissues of mice:the expression of PPAR-amRNA in liver tissues of mice in the model group was significantly decreased than that of normal group（P<0.05）.Compared with the model group,there was a significant increase in each administration group（P<0.05）.Comparison between groups showed that the high-dose group of Baogan Decoction was significantly higher than the medium-dose and low-dose groups（P<0.05）,while the low-dose group of Baogan Decoction was significantly lower than the high-dose and medium-dose groups（P<0.05）.Conclusion:1 Baogan Decoction can reduce serum transaminase of mice with chronic chemical liver injury induced by CCl₄,inhibit the liver lipid peroxidation reaction,promote the oxidation of free fatty acids,and have a protective effect on the chronic chemical liver injury induced by CCl₄.2 The liver protective effect of Baogan Decoction is related to the regulation of Ras/Raf/MEK/ERK signaling pathway.3 The effect of Baogan Decoction is more ideal in medium and high dose groups.Among them,the effect of reducing serum transaminase and inhibiting free radical to start lipid peroxidation was the best in Baogan Decoction.Baogan Decoction can regulate the expression of key factors in Ras/Raf/MEK/ERK signaling pathway with high dose.