Relationship Between Neurturin Dynamic Expression And Cardiac Vagal Neural Remodeling After Myocardial Infarction

Background and objectsCardiac is dominated by sympathetic and vagal nerve, the balance between which is very important for maintaining the stability of cardiac electrophysiology. After myocardial infarction(MI), autonomic nervous injury, necrosis, regeneration and reconstruction associate with cardiac electrical stability changes, while the arrhythmia susceptibility incidence increase.NRTN is a member of the glial-cell-line-derived neurotrophic factor (GDNF) family, a kind of neural plasticity neurotrophic factor. NRTN can promote cholinergic neurons projections extending and has a positive regulatory effect on cardiac vagal nerve’s growth, proliferation and differentiation. Mabe’s studies have shown that the distribution of the the NRTN receptor GFRa2in myocardium is closely related to the vagal innervation in auricle and ventricle. It also reveals notable deficits of cholinergic neuron and nerve fibre in neurturin knockout mice, particularly a87%reducion of cholinergic nerve density at the sinoatrial node. These experiments provide indirect evidence that NRTN has an essential role in establishing cholinergic innervation of the heart. But the relationship between neurturin dynamic expression and cardiac vagal neural remodeling under the state of the disease, especially after MI, has not been reported.The main objects of this study are:(1) To observe the features of cardiac vagal neural remodeling after MI.(2) To investigate the relationship between the dynamic expression of neurturin and vagal neural remodeling after MI.Methods54male SPF Wistar rats were randomly assigned to six groups:3days after MI (n =10),1week after MI (n=10),4weeks after MI (n=10) and three corresponding sham-operated groups (n=8). The left anterior descending coronary artery was ligated to create rat MI model. The sham-operated groups were only thoracotomy threading, without ligation. Heart tissue was sampled from the infarct border and noninfarct left ventricular free wall (LVFW). RT-PCR and western blot were used to examine NRTN mRNA and protein expression. RT-PCR and immunohistochemistry were used to measure the innervation of choline acetyltransferase (ChAT)-positive nerve fibers.ResultsA few minutes after ligate the left anterior descending coronary artery, we can found that the myocardium’s color become purple and pulse weakly in the artery ligation regional. Compared with corresponding sham-operated group, the expressions of NRTN mRNA and protein significantly increase in infarct border at1week after MI, which were higher than those at3days and4weeks after MI (P<0.01). RT-PCR and immunohistochemistry methods found that ChAT-positive nerve fibers become more coarse and show disorderly distribution in infarction surrounding after myocardial infarction. The expressions of ChAT-positive nerve fibers and its mRNA significantly increase at1week and4weeks after MI, which were higher than those at3days after MI(P<0.01). Moreover, compared with corresponding sham-operated group, the ChAT expression decreased at3days after MI mainly because ischemia and hypoxia can cause nerve damage, necrosis. Gene and protein expression changes of NRTN and ChAT in left ventricular free wall are not as obvious as that infarct border.Conclusion(1) Vagal nerve injury, necrosis and remodeling surely exist after myocardial infarction.(2)The dynamic expression of NRTN after MI is closely related to cardiac vagal neural remodeling. Regulating NRTN expression may be a potential therapeutic target for improving cardiac autonomic nervous balance and the prognosis after MI.