HGF Alleviates Ischemia And Reperfusion Injury In Cardiomyocytes By GSK3β Inhibition And Autophagy Promotion

Objective Myocardial infarction(MI)is an increasingly important in the lethality cardiovascular disease and the study of its special pathological process and molecular mechanism has also been increasingly sophisticated in recent years.Studies implicated that autophagy has a great influence in the progress and prognosis of the MI.GSK3β as a downstream protein of HGF signaling pathway,the strength of its activity play an important role in HGF alleviates ischemia and reperfusion injury(IRI)in cardiomyocytes.The present study was conducted to investigated the effect and mechanism of the activity of GSK3βregulated by HGF in protecting myocardical IRI.Methods Excised cardiomyocytes of rats were divided into 7 groups : normal control group,ischemia and reperfusion(I/R)control group,I/R+HGF activator group,I/R+HGF+GSK3β-Ad-GFP group,I/R+HGF+GSK3β-Ad-wt group,I/R+HGF+GSK3β-Ad-K85 A group and I/R+HGF+GSK3β-Ad-S9 A group.The activity of GSK3β was controlled by the method of Adenovirus infection.The total cellular proteins were collected under above conditions.The expression of signaling pathways proteins such as HGF,Akt,GSK3β,LKB1,AMPK and autopgagy-related proteins LC3 B,Beclin1 were detected by Western blot.Results Compared with normal control group and I/R group,Western blot results showed that HGF could improved the expression of its downstream proteins(pAkt、pGSK3β、LKB1、AMPK)and autophagy-related proteins(LC3B、Beclin1)(P<0.05);under the action of HGF activator,the inactivation of GSK3β(Ad-wt and Ad-K85 A group)could increased the expression of its downstream proteins(LKB1、AMPK)and autophagy-related proteins(LC3B、Beclin-1)(P<0.05).however,the above scenarios was reversed in the persistently activated of GSK3β group(Ad-S9 A group)(P<0.05).Conclusion In myocardial ischemia and reperfusion injury of rats,enhanced the expression of HGF could improved the phosphorylation of GSK3β at Ser9 site and then inactivated,which reduced the inhibition of its downstream proteins,like LKB1、AMPK,improved the autophagy and protected the cardiomyocytes in IRI.