Effect Of The Capsaicin Sensitive Senory Nerves And Its Neuropeptide On Myocardial Injury In Acute Myocardial Infrarction And Related Mechanisms Study In Rat

Ischemia heart disease (IHD)is one of the most important of adult mortality in Western countries. It had become the second of adult mortality in our country. In order to treat and prevent, it is important to know its pathogenesy. For many years studies on the neuronal control of myocardial injury in IHD have focused on the antagonistic actions of sympathetic and parasympathetic branch of the autonomic nerves. For the past few years, effect of the capsaicin sensitive nerves and its neuropeptide in IHD is more and more important. However, its exact action and mechanism on IHD is unknown.Objective:The purpose of this study was to investigate the effect of the capsaicin sensitive nerves and its neuropeptide(substance p and calcitonin gene related peptide) on myocardial injure in acute myocardial infarction(AMI) and related mechanisms.Methods:There are four parts in this research.1 The present study evaluated the effect of the capsaicin sensitive nerves denervation on the radiant heat tail flick test and concentration of Sp or CGRP in DRG or left ventricle myocardium.The newborn male Sprague-Dawley rats within 48 hours of birth were randomly divided into two groups.Group denervation(D) with treatment capsaicin 50mg/kg SC.Group control(normal, N) without treatment capasaicin.Eight to twelve weeks after feeding, the radiant heat tail flick latency period was measured. The concentration of SP or CGRP in DRG or left ventricle myocardium were detected by ELASA or IHC.2 This present study detecded the change of SP or CGRP in DRG or left ventricle myocardiμm during AMI by coronary artery occlusion(CAO). The healthy male rats were divided into two groups. Group denervation(D)and Group control(normal,N); Each group were divided into two subgroup; CAO group with left the left anterior branch of coronary artery occlusion; SHAM group without left the left anterior branch of coronary artery occlusion.The concentration of SP or CGRP in DRG or ischemia myocardium after CAO 3h and 6hwere measured by ElASA or IHC.The SPmRNA and CGRP-αmRNA\CGRP-βmRNA in DRG or ischemia myocardium were mesured by real-time Rt-PCR.after CAO 3h and 6h.3 The left anterior descending branch of coronary artery was ligated in anasthesizd Sprague-Dawley(SD) rats(8-12w) with or without treatment of capsaicine in neonatal rats. Left ventricle infract size and blood serμm cardiac troponin I(cTnI) and apoptosis of the myocardiμm insulted by AMI were assessed after AMI 3h and 6h Apoptosis of the myocardiμm insulted by acute myocardial ischaemia and infarction was assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling and caspase assay.4 The antagonists of NK1 and CGRP receptor was performed on 12 week old normal male Sprague-Dawley rats to evaluate the cardioprotective effects of endogenous SP and CGRP by comparing the difference in the infarct size of left ventricule after CAO3h.Results1 The radiant heat tail flick latency period was significantly increased in Group denervation(D). (n=6,P<0.001) concentration of SP or CGRP in DRG or left ventricle myocardium were significantly decreased in Group denervation(D). (n=6,P<0.01).2①The concentration of SP in ischemia myocardium was significantly increased after CAO3h with or without capsaicin treatment in neonatal rats.(n=6,P<0.05 VS SHAM).However, campared with normal rats, The concentration of SP in ischemia myocardium was Significantly decreasd in group denervation(D) (P<0.05). Campared with CAO 3h,The concentration of SP in ischemia myocardium of two group were downregulated after CAO 6h. No statistical differences was found after CAO 6h between group denervation and group normal. The concentration of SP of DRG in group denervation was more increased than group normal after CAO (p<0.05). Beside D-CAO6h, The concentration of SP of DRG were upregulated after CAO.(P<0.05, VS SHAM).②The concentration of CGRP in ischemia myocardium was significantly decreased in group devernation (P<0.05,VS group normal) The concentration of CGRP in ischemia myocardium was significantly upregulated after CAO3h with or without capsaicin treatment in neonatal rats.(P<0.05). No statistical differences was found after CAO 6h between group denervation and group normal(P>0.05).The concentration of CGRP in DRG was more decreased than group normal after CAO in group denervation (n=6,p<0.05).Compared with group CAO3h,a significant increased was detected in N-CAO6h.but no deference in D-CAO 6h.③The levels of SP mRNA in ischemia myocardium was upregulated after CAO in group denervation (VS group normal P<0.05).The levels of SP mRNA in DRG was decreased after CAO in group denervation(VS group normal P<0.05)④The levels of CGRP-amRNA or CGRP-βmRNA in ischemia myocardium was upregulated after CAO in group denervation (VS group normal P<0.05).The levels of CGRP-amRNA or CGRP-PmRNA in DRG was decreased after CAO in group denervation(VS group normal P<0.05).3 The myocardium injury after AMI, defined by increased left ventricular infarct size, blood serμm cTnI and apoptosis, was more sever in Capsaicin treatment in neonatal rats(Denervate) than in normal rat(Normal) (P<0.05) 4 The area of infarction (AI) of left ventricule after CAO3h was more sever in pretreated by antagonists of NK1 and CGRP receptor than in normal.Conclusion:Deletion of capsaicine sensitive afferent nevers enhances myocardial injury in acute myocardial infarction in rats.Endogenous CGRP and SP reduce myocardial injury in acute myocardial infarction in rats.