| Objective: Taking Ferroptosis,a new cell death mode,as the entry point,to explore the effect relationship between autophagy signal and Ferroptosis at the level of ACLF disease and the therapeutic mechanism of JDHY granules in the intervention of Ferroptosis in ACLF liver cells.Methods: 70 healthy SD rats were randomly divided into 5 groups according to the random number method,namely,control group 10(group A),ACLF group 15(group B),JDHY granule group 15(group C),ACLF+autophagy inhibitor 15(group D),JDHY granule+autophagy inhibitor 15(group E).ACLF rat model was established.Rats in the JDHY Granule group and the JDHY granule+autophagy inhibitor group were given 16.28/kg JDHY granule by gavage 3 days before membrane formation and continued to 48 h after model formation,twice a day at an interval of 12 h.The volume of gavage fluid was 4ml/100 g body weight per day.Control group,ACLF group and ACLF+autophagy inhibitor group were given equal amount of distilled water instead.Serum and liver tissues were collected after membrane formation.Liver histological changes were detected by HE and Masson,liver function indexes of AST,ALT and TBIL were detected by biochemical analyzer,iron concentration was detected by elisa,and autophagy(LC3I/LC3 II and Beclin-1)and key Ferroptosis proteins(FTH1 and Tf R1)were detected by Western Blot.Results: Compared with group B,the decrease of AST,ALT and TBIL in group C was statistically significant(P < 0.05),while the decrease of ALT and TBIL in group D was statistically significant(P < 0.05).Compared with group D,AST,ALT and TBIL in groups C and E were significantly decreased(P < 0.05).Compared with group C,ALT and TBIL in group E showed a downward trend,and AST showed statistical differences(P < 0.05).HE and Masson staining found that compared with group B,group C,group D and group E in cell necrosis,apoptosis and liver regeneration cells arranged in has obviously improved,which improve the most significant group E,prompt blood detoxification slow granule can protect and acute liver failure rat liver function and alleviate liver tissue pathological damage,and the mechanism may be related to reduce the excessive autophagy activation ACLF.Western Blot showed that C and D could effectively inhibit the expression of autophagy proteins(LC3I/LC3 II,Beclin-1)and key Ferroptosis proteins(FTH1,Tf R1)compared with group B(P < 0.05).Compared with group C,the decreased expressions of LC3I/LC3 II,Beclin-1 and FTH1 in group E were statistically significant(P < 0.05).The changes of iron ion concentration and Ferroptosis protein expression were roughly the same between groups,group B > group D > group C > Group E > group A,suggesting that detoxification and stasis may inhibit the overexpression of autophagy protein,reduce iron metabolism in liver cells,and then interfere with Ferroptosis to realize the antagonistic effect of ACLF.Conclusion(s): In ACLF disease level,the occurrence of Ferroptosis against the development of the disease prognosis and autophagy expression was positively to the relationship with Ferroptosis occurred,and detoxification of blood particles can be adjusted by reducing liver cell autophagy signal and liver cell iron ion concentration,inhibit autophagy proteins and iron death protein expression,effectively protect ACLF rat liver function and alleviate liver tissue pathological damage,Improving the state of liver regeneration plays a biological role in intervening the process of ACLF disease. |
