ABSTRACT
Aim: To investigate the feasibility of recombinant adeno-associated virus serotype9 (rAAV9) mediated nerve growth factor (NGF) transfection in diabetic rats by intramyocardial injection, and to confirm the protective effect of this method on diabetic cardiac autonomic neuropathy. Methods: At 4th week after the establishment of diabetic model, recombinant adeno-associated virus (rAAV9-NGF) carrying NGF gene was injected into the heart of rats. Five weeks later, the distribution of NGF, calcitonin gene-related peptide (calcitonin gene-related peptide, CGRP) and nerve fibers were detected by immunofluorescence. Hemodynamic parameters were used to evaluate cardiac function, and ELISA method was used to detect the expression of NGF, CGRP in myocardium. Results: The exogenous gene NGF mediated by rAAV9 could be stably transfected and over-expressed in the myocardium of diabetic rats. The left ventricular systolic pressure, heart rate, and maximal rate of increase of left ventricular pressure significantly decreased, the left ventricular end-diastolic pressure and the maximal decrease rate of left ventricular pressure significantly increased, and the cardiac function was improved. NGF, CGRP protein in myocardial tissues were up-regulated, and immunofluorescence showed that the decrease of NGF, CGRP and nerve fibers in myocardial tissues could be partially reversed after transfection. Conclusions: Intramyocardial injection of NGF gene can effectively enhance the expression of NGF and promote the growth of nerve fiber, exerting a protective effect in diabetic rat heart.