Experimental Study Of The NRG-1 Treatment In Diabetic Cardiomyopathy Rats

OBJECTIVE:To observe the influence of diabetic cardiomyopathy STZ-induced by interfering with NRG-1/ErbB signaling pathways, which may also provide a new target treatment for diabetic cardiomyopathy.METHODS:1.Fifty male SD rats aged 8 weeks (weight 250-300mg) were randomly divided into 2 groups:normal group(n=10) and model group(n=40).Diabetes in the model group were induced by a single intraperitoneal injection of streptozotocin at the dose of 70mg/kg. after one week, fasting plasma glucose levels were measured, and the rats with the plasma glucose above 16.7mmol/L were considered as successful diabetic models, and then were randomly divided into NRG-1 group (n=11): received recombinant NRG-110μg/kg(every other day, a total of 2 weeks), Herce group (n=12):injection of the same method NRG-1 addition,2 times per week intravenously trastuzumab (10μg/kg, a total of 2 weeks), DCM group (12):by same method only tail intravenous saline 2 weeks,then the three group of rats were reared under the same conditions for 2 weeks.3.The typeⅠ,Ⅲcollagen mRNA expression were detected by.RT-PCR method andⅠ/Ⅲcollagen mRNA ratio was compared,Masson special staining method was used for the determination of collagen volume fraction (CVF). and measured rat heart inner diameter of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD), calculated left ventricular ejection fraction (LVEF) and left ventricular short axis shorten rate (FS) by ultrasonic diagnostic instrument, to evaluate cardiac function.RT-PCR assayed comparison of ANP, BNP mRNA expression; Tunel method detected Myocardial cell apoptosis, RT-PCR detected the P53mRNA expression of apoptosis-related genes.RESULTS:1. Compared with the Herce group and DCM group, LVEDD/LVESD mean was lower, LVEF/FS mean increased significantly,With ANP, BNP mRNA expression decreased (P<0.05) in NRG-1 group, compared with the DCM group, cardiac function and ANP, BNP mRNA expression of Herce group was no statistically significant terms (P> 0.05).2. Compared with the Herce group and DCM group,Ⅰ,Ⅲcollagen mRNA expression of the NRG-1 group decreased, and theⅠ/Ⅲcollagen mRNA ratio is also lower (P <0.05).compared with the DCM group, the Herce group showed no significant differences (P> 0.05), and Masson staining of collagen results suggest that the collagen volume fraction of NRG-1 group compared with the Herce group and DCM group decreased to normal level, compared with the DCM group, no significant difference between the two groups.3. Compared with the Herce group and DCM group, Tunel assay showed that the NRG-1 group significantly reduced the number of cardiomyocyte apoptosis. Between the Herce and DCM group, there were no significant statistical difference; compared with Herce group and the control group, P53mRNA of NRG-1 group downregulated (P<0.01), Herce group and DCM group, P53mRNA increased expression, and had no significant difference between groups (P> 0.05).CONCLESION:NRG-1/ErbB signaling pathways may be involved in the pathogenesis of diabetic cardiomyopathy. Exogenous administration of NRG-1 can reduce myocardial collagen deposition; inhibit myocardial apoptosis, which play its protective mechanism to delay the process of development of heart failure.