Effect Mechanism Of Xuefuzhuyu Decoction On Regulating LPS/p38MAPK Signaling Pathway In The Treatment Of NAFLD

Objective:To establish C57BL/6J Apoe^-/-mice of non-alcoholic fatty liver disease?NAFLD?animal models and Intervened with Xuefu Zhuyu Decoction in order to explore the effect of Xuefu Zhuyu Decoction on neutrophil granul ocytes infiltration in mice with NAFLD.Also,explore the mechanism of action to provide more theoretical basis for clinical treatment of NAFLD.Method:Selection of 30 C57BL/6J Apoe^-/-mice,they were randomly divided into blank group,model group and experimental group.They were intervened by combination of high fat feed and ultra-low dose LPS to establish the NAFLD model and Xuefu Zhuyu Decoction was used to treat four weeks.Use HE staining and oil red O staining to observe the pathological changes of liver.Use Flow cytometry to detect the number of CD14⁺CD11b⁺Ly6G⁺cells in peripheral blood of mice.Use ELISA method to measure the concentration of KC?MIP-2?MPO of mice.And Western blot was used to detect the Protein expression of p38MAPK,MKP7,Caspase-3,PARP and etc of mice.Results:Liver steatosis and inflammatory infiltration in the experimental group were better than those in the model group;It was significant that the percentage of CD14-CD11b⁺Ly6G⁺cells in peripheral blood of mice in the experimental group was less than the model group,and the difference is in a statistically meaningful way.?P<0.05?;The concentration of MIP-2 in peripheral blood of mice in the experimental group was considerably below the concentration in the model group.And it was between a statistically significant discrepancy.?P<0.05?;Compared with the model group,the concentration of KC factor in peripheral blood of mice in the experimental group was sharply lower,and the diversity was notable.?P<0.05?;The expression of PARP protein in the liver of mice in the experimental group was fewer than that in the model group;The expression of Caspase-3 protein in the liver of mice in the experimental group was significantly fewer than that in the model group;The concentration of MPO in the experimental group was similar to that in the model group,and there was no significant difference?P>0.05?;The expression of MKP7protein in experimental group was obviously more than that in model group.The expression of p38MAPK protein in experimental group was lower than that in model group.Conclusion:1.High-fat diet combined with subclinical dose of LPS intraperitoneal injection can successfully prepare the animal model of NFALD.2.Xuefu Zhuyu Decoction can effectively control and reduce liver lobular inflammation and steatosis.3.Xuefu Zhuyu Decoction can inhibit the activation of neutrophils which were stimulated by LPS,by reducing the concentration of chemokines KC and MIP-2.It can also inhibit the activation of neutrophils in peripheral circulation.4.Xuefu Zhuyu Decoction can inhibit the apoptosis of NAFLD hepatocytes by down-regulating the expression of Caspase-3 protein and lysed PARP protein.;5.Xuefu Zhuyu Decoction can promote the expression of MKP7 protein,inhibit the expression of p38MAPK protein and restrain the signal pathway of LPS/p38MAPK.