Yin Chen Si Ling Granules Protect The ER Stress-induced Acute Failing Liver Mechanisms Of Cell Apoptosis

Objective:In animal experiments,To explore the protective effect of Yin Chen Si ling granules on hepatocyte apoptosis induced by ER stress in mice with acute liver failure by studying related proteins and PPAR αunder ER stress in liver tissue,It provides a theoretical basis for the clinical treatment of Chen Si ling granules in acute liver failure.Methods:With the comparison of ER stress inhibitors,Making up model of acute liver failure in mice after Yin Chen Siling granule intervention in mice and observing mouse liver work,liver pathology,hepatocyte apoptosis,liver ER stress-related signaling molecules and PPARα protein expression To investigate the regulation of hepatocyte apoptosis mediated by ER stress in mice with acute liver failure.detailed procedures: 1.Liver function results: Both the control group and each TCM group could reduce the liver function level in mice with acute liver failure,and the concentration of TCM in each TCM group was positively correlated with the level of liver function improvement in the liver function,among which the improvement of liver function was the most obvious in the high-dose group.2.HE staining of liver tissue: normal liver structure;the model group showed hemorrhage,hepatic lobular structure,inflammatory cell infiltration and degeneration and necrosis of hepatcells;pathological changes of each TCM group and control group were reduced compared with the model group.3.TUNEL and WB test results: compared with the normal group,CHOP and GRP 78 protein levels were significantly increased(P <0.01),apoptosis was significantly increased and PPAR α activity was significantly decreased(P <0.01);compared with the model group,CHOP,GRP 78 protein levels and hepatocyte apoptosis decreased,and the α activity of PPAR was increased.In each TCM group,the TCM concentration was negatively correlated with CHOP,GRP 78 protein level and hepatocyte apoptosis level,and positively correlated with PPAR α protein level.Moreover,CHOP,GRP 78 protein levels and hepatocyte apoptosis were lower,with higher GRP 78 activity.Results:1.Liver function results: Both the control group and each TCM group could reduce the liver function level in mice with acute liver failure,and the concentration of TCM in each TCM group was positively correlated with the level of liver function improvement,with the most obvious improvement in the high-dose group.2.HE staining of liver tissue: normal liver structure;the model group showed hemorrhage,hepatic lobular structure,inflammatory cell infiltration and degeneration and necrosis of hepatcells;pathological changes of each TCM group and control group were reduced compared with the model group.3.TUNEL and WB test results: compared with the normal group,CHOP and GRP 78 protein levels were significantly increased(P <0.01),apoptosis was significantly increased and PPAR α activity was significantly decreased(P<0.01);compared with the model group,CHOP,GRP 78 protein levels and hepatocyte apoptosis decreased,and the α activity of PPAR was increased.In each TCM group,the TCM concentration was negatively correlated with CHOP,GRP 78 protein level and hepatocyte apoptosis level,and positively correlated with PPAR α protein level.Moreover,CHOP,GRP 78 protein levels and hepatocyte apoptosis were lower,with higher GRP 78 activity.Conclusion: 1.Yin Chen Si ling granules can effectively improve the liver function,reduce the degree of liver tissue pathology damage and reduce liver cell apoptosis in mice with acute liver failure.2,4-PBA can inhibit ER stress and protect against hepatocyte apoptosis in acute liver failure in mice.3,inhibition of ER stress promotes the expression of PPARα induced by D-Gal N /LPS in mice with acute liver failure.4.Yin Chen Si ling granules protect ER stress-mediated hepatocyte apoptosis in acute liver failure,and the mechanism may be related to the regulation of ER stress-related molecule GRP 78,CHOP expression levels and activation of PPAR α to reduce hepatocyte apoptosis.