Decreased Expression Of TRPV1 Impair The Functional Recovery Of Postischemic Cardiac Injury In Diabetes Mellitus Mouse

Objection:Diabetes mellitus(DM)is a major risk factor for coronary atherosclerosis. Clinically,DM occurred in about one third of patients with acute myocardial infarction. The high morbidity rate of myocardial infarction in patients with DM may associate with diffuse coronary atherosclerotic plaque,but the specific mechanism is still unclear."What's more,the medical and surgical therapy in patient with myocardial infarction and DM is less effective than those in nondiabetic patients.It is well known by research that there are many sensory nervous endings distributed on the cardiovascular system including adventitia of the vessels and the heart.The transient receptor potential vanilloid type 1(TRPV1)is located in the sensory nervous fibers and could modulate the cardiac function.The degeneration of nerve fibers has been observed both in DM animals and patients,which necessitates the further study in the relationship between ischemic cardiac injury and alteration of TRPV1 in diabetic hearts.This discussion is expected to be benefit to uncover the mechanism in diabetic patients complicated with myocardial infarction.Methods:The ICR diabetic and normal mice were randomly separated into 6 groups 3 of them were diabetic groups,the other 3 were normal groups from alive mouse.Hearts were evacuated DM model was established by intraperitoneally injection of streptozotocin(STZ)into chests and were hanged on the Langendorff steadly for 30mins.All hearts should experience under room temperature.The expression of TRPV1 and CGRP in the hearts was determined by western blot and radioimrnunoassay respectively.During the ischemia/reperfusion(I/R)process,the cardiac function including left ventricular end-diastolic pressure(LVEDP),left ventricular developed pressure(LVDP),maximum positive and negative values of first derivative of left ventricular pressure over time(±dp/dtmax)and coronary flow(CF)were measured by Medlab system.The effluent from the hearts was collected for the measurement of lactate dehydrogenase(LDH)with ELISA kit.All data were expressed by mean±standard error.The differences among groups were defined by single factor variance analysis.If the difference is significant,then the P＜0.05 was considered significant.Results:The expression of TRPV1 and CGRP in DM hearts was both significantly lower than those in the Non-DM hearts(P＜0.01).Compared with Non-DM hearts,the LVEDP was increased(P＜0.01),and the LVDP±dp/dtmax,CF were all deceased significantly in DM hearts(P＜0.05).The concentration of LDH released from DM hearts was significantly higher than Non-DM hearts.Pretreatment with capsaicin in Non-DM hearts was able to improve the postischemic recovery function and decrease the LDH release significantly(P＜0.05),whereas it failed in DM hearts.Pretreatment with CGRP in both Non-DM and DM hearts protected the hearts against the ischemic injury.Conclusion:The diabetes probably impairs the expression of TRPV1 and synthesis of CGRP, which maybe essential to the more severe deterioration of diabetic hearts after ischemic injury.