Activation Of Transient Receptor Potential Vanilloid 1/TRPV1 Protects Cardiomyocytes Against Apoptosis In Acute Myocardial Infarct Mice By Closing Mitochondrial Permeability Transition Pore

Backgroud: Transient receptor potential vanilloid 1(TRPV1)activation releases the neuropeptide in myocardial ischemia,which plays a protective role in reducing myocardial apotosis after myocardial infarction(MI).However the mechanisms of TRPV1 activation in inhibiting apoptosis is unknown.The opening of mitochondrial permeability transition pore(MPTP)is known to be closely related to myocardial ischemia reperfusion injury,and inhibition of its opening may play a role in myocardial protection.However,it is unclear whether the protective role of TRPV1 is related to the opening of MPTP.Object: To investigate whether transient receptor potential vanilloid 1 activation inhibit apoptosis via inhibition of mitochondrial permeability transition pore opening in mice after myocardial infarction.Methods: In this study,myocardial infarction(MI)models were established in wild type(WT)and TRPV1-null mutant(TRPV1-/-)mice.Cyclosporin A(CSA)was administrated before MI to inhibit the opening of MPTP.Tetrazolium chloride(TTC)staining was used to detect the infarct size.Apoptosis index was detected by Td T-mediated d UTP nick end-labeling(TUNEL).the opening of MPTP was determined by colorimetric assay,Western blot was applied to measure the expression of caspase 3,caspase 9,Bcl-2,Bax,p53,Cyt-C.Results: Compared with Sham group,infarct size,apoptosis index,absorbance value,the expression of caspase 3,caspase 9 activity were enhanced post MI in both TRPV1-/-and WT mice.The apoptosis index,absorbance value and the expression of caspase 3,caspase 9 in TRPV1-/-mice were higher than those in WT mice.However,the expression of Bcl-2/Bax and p53 were lower in TRPV1-/-mice compared with WT mice.The application of CSA significantly reduced the infarct size,absorbance value,the expression of caspase 3 and caspase 9,apoptosis index and increase the Bcl-2/Bax ratio in TRPV1-/-mice.The expression of Cyt-C protein in mitochondria was increased in TRPV1-/-mice,but no significant improvement in WT mice.Conclusion: These results demonstrated that TRPV1 may play a protective role in apoptosis post acute myocardial infarction via regulating MPTP.