Exploration on the regulation mechanism of LXR-α/SREBP-1 c pathway in MASH rats based on the theory of"liver and large intestine communication"
Objective To explore the therapeutic mechanism of Xiaoyao pills on MASH rats,and to clarify the guiding significance of the theory of"connecting liver and large intestine"in TCM.Methods A total of 24 adult male SD rats were selected and randomly divided into Control group(8 rats)and Model group(16 rats).The Control group was fed with ordinary diet,and the Model 0 group was fed with high-fat diet,with subcutaneous injection of 40％carbon tetrachloride into the back,as well as with hunger and satiation disorder and tail-clip stimulation.4 weeks later,the Model 0 group was randomly divided into Model group and Xiaoyao pill group(XYW group),with 8 animals in each group.The rats in XYW group were given Xiaoyao pill and the other two groups were given normal sa-line.After 4 weeks of administration,the liver function and liver fat content of rats were measured respectively.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of liver tissue.The damage of intestinal barrier was observed by Alcian blue-periodate Shev(AB-PAS)staining.The levels of inflammatory factors in rat liver homogenate were determined by ELISA kit.The mRNA expressions of LXR-α,SREBP-1c and Nrf2 in liver and Claudin1,ZO-1,SREBP-1c and Nrf2 in colon were determined by qRT-PCR.The protein expression of LXR-α,SREBP-1c and Nrf2 in liver and Claudin1,ZO-1,SREBP-1c and Nrf2 in colon were detected by Western blot.Results Compared with Control group,the levels of serum ALT,AST and liver homogenate T-CHO,TG,LDL-C,IL-8,IL-17 and TNF-α in Model group were increased(P＜0.05),while the levels of HDL-C,IL-10 and TGF-β1 were decreased(P＜0.01).In Model group,the mRNA expressions of LXR-α and SREBP-1c in liver tissue were increased(P＜0.001),the mRNA expressions of Nrf2 were decreased(P＜0.01),and the mrna expressions of Claudin1,ZO-1 and Nrf2 in colon tissue were decreased(P＜0.01).The expression of SREBP-1c was increased(P＜0.01).The protein levels of LXR-α and SREBP-1c in liver tissue of Model group were increased(P＜0.01),while Nrf2 was decreased(P＜0.05),the protein levels of Clau-din1,ZO-1 and Nrf2 in colon tissue were decreased(P＜0.001),and SREBP-1 c was increased(P＜0.001).Conclusion Xiaoyao Pill has a certain therapeutic effect on MASH rats,and its therapeutic mechanism may be related to reducing inflammation,oxidative stress and inhibiting fatty acid accumulation.Protecting the intestinal mucosal barrier from damage can effectively reduce the damage of the liver.The theory of"connecting the liver and the large intestine"has certain guiding significance for MASH treatment.
Metabolic related steatohepatitisXiaoyao pillLiver in the large intestineSterol regulatory element binding protein-1C(SREBP-1c)Nuclear factor E2-related factorNif2Liver X receptor α(LXR-α))
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