Bioactive Peptides Reverse The Hepatic Fibrosis Of SD Rats Via PINK1/PARKIN-mediated Mitophagy

Objective To study the effect of bioactive peptide on liver fibrosis induced by CCl₄ in SD rats,and explore the mechanism of bioactive peptide regulating the mitophagy mediated by PINK1/PARKIN.Method Forty female SD rats were randomly divided into blank group,model group,trial group and protecting liver soup group,with 10 rats in each group.Except for the blank group,the rats in the three groups were injected with CCl₄intraperitoneally twice a week,and the blank group was injected with the same amount of normal saline.After4 weeks,the trial group received intragastric administration of bioactive peptide,the protecting liver soup group received intragastric administration of protecting liver soup,and the blank group and the model group received intragastric administration of normal saline twice a week.After 4 weeks of treatment,the animal was weighed and died after anesthesia.Blood was collected and liver tissues were weighed.After calculating the liver index,part of the liver was fixed to prepare the paraffin section,and part of the liver was frozen in liquid nitrogen.HE staining and MASSON staining were performed in paraffin sections of the liver,and the expression levels of TGF-?1,PINK1 and PARKIN protein were analyzed by immunohistochemical staining.Liver function was determined by the detection of serum biochemical indexes ALT and AST.The levels of MMP1 and TIMP1 in liver tissues were detected by ELISA.The expression of TGF-?1,PINK1 and PARKIN was detected by RT-q PCR.Result Compared with the blank group,the liver index of rats in the model group was increased,the content of ALT and AST were increased?P<0.05?,and the liver tissue showed serious lesions,which proved the success of CCl₄ modeling.Compared with the model group,the liver index of rats in the protecting liver soup group and the trial group decreased,the levels of ALT and AST down-regulated,and the histological staining results showed that the degree of liver tissue damage was inhibited.ELISA showed that the expression level of MMP1 protein was increased,and the expression level of TIMP1 protein was decreased.Immunohistochemical staining results and q PCR results further indicated that the treatment with active peptide and protecting liver soup up-regulated the expression levels of PINK1 and PARKIN,while significantly inhibited the expression levels of TGF-?1.Conclusion CCl₄ can mediate the expression levels of TGF-?1,PINK1 and PARKIN,thereby regulating the mitophagy process and inducing liver fibrosis in SD rats.Both the trial group and the protecting liver soup group could promote mitophagy by up-regulating the expression level of PINK1/PARKIN and down-regulating the expression level of TGF-?1.Both treatments could delay the change of liver structure and have the same protective reversal effect.