Clinical And Experimental Study Of Lidan Mixture Against Oxidative Stress In The Treatment Of Cholestatic Liver Fibrosis

Objective:Through consulting the materials and learning to be familiar with the relationship between infantile cholestasis,cholestatic liver fibrosis and oxidative stress in the literature of traditional Chinese and Western medicine,we adopted the therapeutic scheme of the prescription based on Lidan Mixture for infantile cholestatic liver fibrosis caused by cholestatic liver disease,and tested the four items of liver fibrosis,liver elasticity test and oxidative stress biological index in the children to observe the clinical efficacy of Lidan Mixture for cholestatic liver fibrosis.At the same time,animal experiments were conducted to observe the effect of Lidan Mixture on cholestatic liver fibrosis model mice induced by DDC diet,explore the mechanism of Lidan Mixture against cholestatic liver fibrosis,and understand the role of oxidative stress in the occurrence and development of cholestatic liver fibrosis,so as to provide the basis for further research on the treatment of cholestatic liver disease in infants with Lidan Mixture.Method:1.Theoretical research: through consulting the ancient books of traditional Chinese medicine and retrieving the ten years "Zhiwang","Wanfang" and "Wei In general " and " pubmed ",the clinical and experimental research articles of cholestatic hepatic fibrosis systematically reviewed the evolution of disease name,etiology and pathogenesis,syndrome differentiation in traditional Chinese medicine,the epidemiological overview,clinical process,risk factors,pathogenesis and treatment in western medicine,as well as the role of oxidative stress in cholestatic hepatic fibrosis,providing new research ideas for the possible role of Lidan Mixture in improving cholestatic hepatic fibrosis.2.Clinical trial study: Blood samples were all from Wuhan Children's Medicine Affiliated to Huazhong University of Science and Technology Hospital,in this study,detailed list of each patient's general situation,main symptoms,secondary symptoms,signs,laboratory indicators,ultrasound room indicators,syndrome differentiation and other indicators according to the inclusion criteria and exclusion criteria were grouped: a total of 40 cases,in the observation group,4 cases of damp-heat fumigation syndrome,8 cases of cold-damp stagnation syndrome,7 cases of stasis and yellow syndrome;in the control group,5cases of damp-heat fumigation syndrome,9 cases of cold-damp stagnation syndrome,and 7 cases of stasis and yellow syndrome.The general data of children in each group were collected,counted and analyzed.The laboratory tests,liver elasticity tests,overall efficacy,and TCM syndrome efficacy were compared between the observation group and the control group.The effects of lidan mixture on the prognosis of children with the same syndrome type were compared between the two groups.3.Animal experiments: Blood samples were taken from C57BL6/J young mice,and the cholestatic hepatic fibrosis model was established.Meanwhile,the blank control group was established and randomly divided into four groups: the model group,the cholagogue mixture group,the fenofibrate group,and the ursodeoxycholic acid group.The blood samples of liver and spleen were collected from five groups after being administered with distilled water,cholagogue mixture,fenofibrate,and ursodeoxycholic acid,to detect blood biochemical indicators and observe pathological changes of the liver.SPSS22.0 and stata14.0 statistical software were used to calculate the liver function biochemical indicators,the four indicators of liver fibrosis and oxidative stress indicators,to observe the effect of Lidan mixture on liver fibrosis and biomarkers of oxidative stress,and to observe the effect of oxidative stress in the improvement of cholestatic liver fibrosis by Lidan mixture.result1 Results of two groups of objective indicators of cholestatic liver fibrosis in clinical experiments Clinical studies showed that the general data of the two groups were comparable,and the retraction time of liver and spleen in the observation group was shorter than that in the control group.After treatment,there were significant differences in TBIL,DBIL,ALP,?-GGT,ALT,AST and TBA between the observation group and the control group.There was no significant difference in MDA and GSH between the observation group and the control group after treatment,and there was a significant difference in SOD between the observation group and the control group after treatment.HA,P-III-P,IV-C,and LN in the observation group were significantly different from those in the control group after treatment.There was significant difference in liver elasticity between the observation group and the control group after treatment.There was significant difference in APRI after treatment between the observation group and the control group.The treatment of cholestatic liver fibrosis in the two groups was generally effective.The total effective rate of TCM syndrome observation group was better than the control group.2 The objective index results of Lidan mixture improving cholestatic hepatic fibrosis in young mice in animal experimentsThe observation results showed that the mice in the normal group had normal conditions,while those in other groups had dark fur and partial alopecia.The liver indexes of the cholagogue mixture group and fenofibrate group were significantly different from those of the model group.The liver index of the ursodeoxycholic acid group was not different from that of the model group.The spleen indexes of the cholagogue mixture group,fenofibrate group and ursodeoxycholic acid group were not significantly different from those of the model group.The liver of the blank group was bright red,while that of the model group was dark black,with a slightly smaller volume.The mice in the Lidan mixture group,fenofibrate group and ursodeoxycholic acid group were dark black,with a slightly larger volume than that in the model group.HE staining of mice in the model group showed significant cholestasis,degeneration and necrosis of hepatocytes,and a large number of inflammatory cell infiltration.Masson staining showed a large amount of collagen deposition,cross-linked into a network structure and incomplete segmentation of pseudolobules.Compared with the model group,the levels of cholagogue mixture group,fenofibrate group and ursodeoxycholic acid group were reduced,with inflammation in the portal area and enlargement of the portal area.The degree of Metavir score fibrosis in the model group and fenofibrate group could reach two points,while the levels of ursodeoxycholic acid group and cholagogue mixture group reached one point.The levels of TBIL,DBIL,ALT,AST,ALP,?-GT,HA,P-III-P,IV-C,LN,SOD,GSH,and MDA in the model group,Lidan mixture group,fenofibrate group and ursodeoxycholic acid group were significantly different from those in the blank control group.The levels of TBIL,DBIL,ALT,AST,ALP,?-GT,HA,P-III-P,IV-C,LN,SOD,GSH,and MDA in the Lidan mixture group,fenofibrate group and ursodeoxycholic acid group were significantly different from those in the model group.The levels of TBIL,DBIL,ALT,AST,ALP,?-GT,HA,PIII-P,IV-C,LN,SOD,GSH,and MDA in the fenofibrate group and ursodeoxycholic acid group were significantly different from those in the Lidan mixture group.conclusion1 After treatment,MDA and GSH of the observation group were ot different from those of the control group,while liver function,SOD,HA,P-III-P,IV-C,LN,APRI and liver elasticity test of the observation group were significantly different from those of the control group.The treatment for cholestatic liver fibrosis in the two groups was generally effective.The total effective rate observation group was superior to the control group in TCM syndrome efficacy.Lidan mixture could improve cholestatic liver fibrosis and reduce the levels of oxidative stress-related markers.2 In the animal experiment,young mice were selected as the subjects.According to the pathological changes of the liver and the changes of levels of TBIL,DBIL,ALT,AST,ALP,?-GT,HA,P-III-P,IV-C,and LN,and the occurrence of cholestasis and liver fibrosis in the mice with cholestatic liver fibrosis induced by DDC,the modeling was successful.The intervention with cholestatic mixture,fenofibrate,and ursodeoxycholic acid could improve the liver pathology of the mice in all groups.Cholestasis,liver fibrosis degree,including lidan mixture effect is the best,according to the changes of the levels of SOD,GSH,MDA,confirmed that markers of oxidative stress and cholestatic liver fibrosis course and severity have consistency,show that oxidative stress in cholestatic liver fibrosis plays an important role.