Research On The Mechanism Of Yinchenhao Decoction On Treating Nonalcoholic Fatty Liver Disease

BACKGROUND:In recent years,non-alcoholic fatty liver disease(NAFLD)is rapidly becoming one of the most common liver diseases in the world.Due to inadequate awareness and supervision of the disease and lack of effective treatment,non-alcoholic Fatty liver has begun to put a huge burden on the medical system.Therefore,actively explor:ing the pathogenesis and treatment of nonalcoholic fatty liver disease is of great significance in preventing the occurrence and development of diseases,reducing the possibility of complications,reducing the incidence of liver transplantation and even mortality.At present,Western medicine has no specific drugs,and the treatment effect is not satisfactory.The traditional medicine of the motherland has a unique understanding of the pathogenesis and treatment of nonalcoholic fatty liver disease.Yinchenhaotang is a famous prescription for treating damp heat and jaundice.It is widely used in the clinical treatment of hepatobiliary diseases because of its characteristics of clearing away heat and dampness and promoting blood circulation.Therefore,it explores its non-alcoholic fatty liver disease.The prevention and control is forward-looking.OBJECTIVE:To study the pathogenesis of non-alcoholic fatty liver disease patients and the relationship between different TCM syndrome types and transient elastography(Fibrotouch);to explore the formation mechanism of non-alcoholic fatty liver model induced by high-fat diet in mice;The mechanism by which the soup treats nonalcoholic fatty liver.Methods:Based on the patient-derived data derived from Fibrotouch,the incidence factors of non-alcoholic fatty liver disease patients were analyzed.The independent sample t test was used to analyze the relationship between different TCM syndrome types and non-alcoholic fatty liver disease(Fatattenuation parameter,FAP).),liver hardness value(Liver Stiffiness Measurement(LSM));the experiment is mainly through tissue section HE staining and oil red O staining,serum ALT,AST,liver tissue TC,TG content,qPCR detection of liver tissue inflammatory factors The mRNA expression levels of M1 and M2 macrophages were explored.The differences between the mice in each group were analyzed.The data were analyzed by independent sample t-test.RESULTS:This study found that NAFLD is the most common form of damp-heat accumulation syndrome.The NAFLD type IV is based on FAP index.The liver-stagnation and spleen-deficiency syndrome is mainly mild fatty liver,and the phlegm-inhibiting syndrome and damp-heat accumulation syndrome are Moderate and severe fatty liver were the main factors,and those with phlegm and blood stasis were mainly fatty liver.From the stage of LSM,the liver stagnation and spleen deficiency syndrome was mainly F0-F1,F1-F2 stage;turbid internal resistance and The indicators of damp heat accumulation are mainly F3-F4 and F4,while those of phlegm and blood stasis are mainly F4.Through animal experiments,high-fat diet can promote the weight gain of model mice,the difference is statistically significant(*P<0.05);at the same time induce the establishment of NAFLD model;promote the spleen weight of NAFLD mice,the difference is statistically significant(*P<0.05);The serum transaminase ALT and AST of NAFLD mice were significantly higher than those of normal mice,the difference was statistically significant(*P<0.05);the content of TC and TG in liver tissue of NAFLD mice was induced.The difference was statistically significant(*P<0.05);the expression levels of inflammatory factors IL-1,IL-10 and TNF-a in liver tissue of NAFLD mice increased,the difference was statistically significant(*P<0.05);The expression level of inflammatory factor IL-6 was not significantly increased(P>0.05).The expression of Ml macrophage marker TNF-a was up-regulated in the liver tissue of mice,and the difference was statistically significant(*P<0.05).However,the expression of M1 macrophage markers iNOS and MCP-1 was not obvious.The difference was(P>0.05).The expression of M2 macrophage markers ARG1,MRC2 and CD 163 in liver tissue of model mice was down-regulated,the difference was statistically significant(**P<0.01,****P<0.0001)..Yinchenhao Decoction can significantly reduce the weight of spleen in mice,the difference was statistically significant(**P<0.01);the blood ALT level was decreased,the difference was statistically significant(*P<0.05)and had no significant effect on blood AST.(P>0.05).(Fig.12)The levels of TG and TC in liver tissue were significantly decreased(Fig.13),and the difference was statistically significant(*P<0.05,***P<0.001).The mice in the Yinchenhaotang group were more mature than the model liver.The expression levels of inflammatory cytokines IL-1,IL-10 and TNF-a were decreased,and the difference was statistically significant(*P<0.05).The expression level of inflammatory cytokines IL-6 was not significantly changed(P>0.05).The expressions of M2 macrophage markers ARG1,MRC2 and CD 163 were up-regulated in the liver tissue of mice with Artemisia decoction.The difference was statistically significant(*P<0.05,**P<0.01);M1 macrophage marker TNF-a expression was down-regulated,the difference was statistically significant(*P<0.05);while the expression of Ml-type macrophage markers iNOS and MCP-1 were not significantly different(P>0.05).The differentiation of macrophages M1/M2(CD163/iNOS)in the Yinchenhaotang group was significantly higher than that in the model group(Fig.16),and the difference was statistically significant(**P<0.01).Conclusion:The syndrome of damp-heat accumulation is the most common among the four syndromes of NAFLD patients.In the FAP index,the liver-stagnation and spleen-deficiency syndrome is mainly mild fatty liver,the phlegm-stagnation syndrome and the damp-heat syndrome are moderate and severe.Fatty liver is the main component,and those with phlegm and blood stasis are mainly fatty liver.From the LSM staging,the liver stagnation and spleen deficiency syndrome is mainly F0-F1,F1-F2 stage;phlegm internal resistance syndrome and damp heat accumulation The witnesses are mainly in the F3-F4 and F4 periods;the ??-interns are mainly in the F4 period.The high-fat diet promotes the differentiation of mouse liver macrophages from M2 to M1,aggravating the development of NAFLD.Yinchenhao Decoction can regulate the expression of inflammatory factors by regulating the expression of M1 type macrophages in the liver of NAFLD mice,and to a certain extent,it can play a role in the treatment of NAFLD.Yinchenhao Decoction can reduce the expression level of inflammatory factors in the pathogenesis of NAFLD in different degrees.This mechanism may be related to the promotion of the differentiation of M2 macrophages in the liver.In the future research,we can further explore the signaling pathways and targeting genes of Yinchenhao Decoction to promote the differentiation of M2 macrophages in the liver.