Effects Of Jie-Du-Hu-Gan Decoction On The Expression Of STAT3 In Rats With APAP-induced Liver Injury

Objective: To investigate the prevention and treatment effect of Jie-Du-Hu-Gan Decoction on drug-induced liver injury(DILI),the liver function index,early biomarkers of liver injury,inflammatory factors in serum,expression of HMGB1 protein,STAT3 gene and protein in liver tissue were detected,meanwhile the mechanism was revealed.Methods: Acetaminophen(APAP)was selected to replicate DILI rat model according to references,and drugs were applied for intervention at the same time.72 wistar rats were randomly divided into normal group,model group,silybin capsule group and high,middle,low dose groups of Jie-Du-Hu-Gan Decoction.The normal group was given distilled water in the morning,while the other groups were given APAP.In the afternoon,normal group and model group were given distilled water,and the rest were given corresponding therapeutic drugs for 30 consecutive days.At the end of the experiment,blood was taken from the femoral artery,and the blood samples were centrifuged to separate serum and plasma.Then the activity or content of serum ALT,AST,TBIL,DBIL,MDH,PON1,GLDH,Arg1,TNF?,IL-6,IL-13 and IL-22 were detected.A portion of liver tissue was frozen with liquid nitrogen,then the expression of STAT3 gene and protein was detected by qRT-PCR and Western Blot.Another liver tissue was put into 4%paraformaldehyde solution,the morphological status of liver tissue was observed by HE staining,and the expression of HMGB1 was observed by immunohistochemistry.Results: Compared with normal group,the activity or content of serum ALT,AST,DBIL,MDH,PON1,GLDH,Arg1,TNF?,IL-6,IL-13,IL-22 and the expression of HMGB1 and p-STAT3 protein in liver tissue of the model group were significantly increased(P<0.05 or P<0.01).Compared with themodel group,the activity or content of serum ALT,AST,DBIL,IL-22 and the expression of HMGB1 in liver tissue in each therapeutic group of Jie-Du-Hu-Gan Decoction were significantly decreased(P<0.05 or P<0.01),at the same time it can counter the liver tissue pathological damage.In the middle dose group,the activity or content of MDH,GLDH,Arg1,TNF?,IL-13,IL-22 and the expression of p-STAT3 protein were significantly decreased(P<0.05 or P<0.01).In the high dose group,the activity or content of MDH,GLDH,Arg1,TNF?,IL-13,IL-22 and the expression of p-STAT3 protein were significantly decreased(P<0.05 or P<0.01).Conclusion: Jie-Du-Hu-Gan Decoction could prevent and treat liver injury caused by APAP,and has a certain effect of liver protection.The mechanism may be reducing the content of inflammatory factors in serum and the expression of HMGB1 and p-STAT3 protein in liver tissue,inhibiting the phosphorylation of STAT3 protein,and then inhibiting the occurrence of liver inflammation,thus achieving the purpose of treatment.