Department of Cardiology, First Affiliated Hospital, Nanchang University, Nanchang 330006, China.
Cardiovasc Diabetol. 2011 Jul 29;10:69. doi: 10.1186/1475-2840-10-69.
Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. The effective treatment strategy for DCM has not been developed.
Rats were divided into 3 groups with different treatment. The control group was only injected with citrate buffer (n = 8). The diabetes group and diabetes treated group were injected with streptozotocin to induce diabetes. After success of diabetes induction, the rats with diabetes were treated with (diabetes treated group, n = 8) or without (diabetes group, n = 8) recombinant human Neuregulin-1 (rhNRG-1). All studies were carried out 16 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate the cardiac function. Apoptotic cells were determined by TUNEL staining. Left ventricular (LV) sections were stained with Masson to investigate myocardial collagen contents. Related gene expressions were analyzed by quantitative real-time PCR (qRT-PCR).
Diabetes impaired cardiac function manifested by reduced LV systolic pressure (LVSP), maximum rate of LV pressure rise and fall (+dp/dt max and -dp/dt max) and increased LV end-diastolic pressure (LVEDP). The rhNRG-1 treatment could significantly alleviate these symptoms and improve heart function. More TUNEL staining positive cells were observed in the diabetic group than that in the control group, and the rhNRG-1 treatment decreased apoptotic cells number. Furthermore, qRT-PCR assay demonstrated that rhNRG-1 treatment could decrease the expression of bax and caspase-3 and increase that of bcl-2. Collagen volume fraction was higher in the diabetic group than in the control group. Fibrotic and fibrotic related mRNA (type I and type III collagen) levels in the myocardium were significantly reduced by administration of rhNRG-1.
rhNRG-1 could significantly improve the heart function and reverse the cardiac remodeling of DCM rats with chronic heart failure. These results support the clinical possibility of applying rhNRG-1 as an optional therapeutic strategy for DCM treatment in the future.
糖尿病心肌病（DCM）是一种发生在糖尿病患者中的心肌疾病，其特征是同时存在收缩和舒张功能障碍。目前尚未开发出针对 DCM 的有效治疗策略。
将大鼠分为 3 组进行不同的治疗。对照组仅注射柠檬酸盐缓冲液（n = 8）。糖尿病组和糖尿病治疗组注射链脲佐菌素诱导糖尿病。糖尿病诱导成功后，用（糖尿病治疗组，n = 8）或不用（糖尿病组，n = 8）重组人神经调节蛋白 1（rhNRG-1）治疗糖尿病大鼠。所有研究均在糖尿病诱导后 16 周进行。进行心导管检查以评估心功能。通过 TUNEL 染色测定凋亡细胞。用 Masson 染色左心室（LV）切片以研究心肌胶原含量。通过定量实时 PCR（qRT-PCR）分析相关基因表达。
糖尿病损害了心脏功能，表现为左心室收缩压（LVSP）降低、左心室压力上升和下降的最大速率（+dp/dt max 和-dp/dt max）降低以及左心室舒张末期压（LVEDP）升高。rhNRG-1 治疗可显著缓解这些症状并改善心功能。糖尿病组的 TUNEL 染色阳性细胞数多于对照组，rhNRG-1 治疗减少了凋亡细胞数。此外，qRT-PCR 检测显示，rhNRG-1 治疗可降低 bax 和 caspase-3 的表达，增加 bcl-2 的表达。糖尿病组的胶原容积分数高于对照组。rhNRG-1 给药可显著降低心肌中纤维化和纤维化相关 mRNA（I 型和 III 型胶原）水平。
rhNRG-1 可显著改善 DCM 慢性心力衰竭大鼠的心功能并逆转心脏重构。这些结果支持在未来将 rhNRG-1 作为 DCM 治疗的可选治疗策略的临床可能性。
