Therapeutic effects of neuregulin-1 in diabetic cardiomyopathy rats
Therapeutic effects of neuregulin-1 in diabetic cardiomyopathy rats
复制标题
神经调节蛋白1对糖尿病心肌病大鼠的治疗作用
DOI：
10.1186/1475-2840-10-69
复制
发表时间：
2011-07-29
影响因子：
9.3
通讯作者：
Li, Zhe
中科院分区：
文献类型：
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作者：
Li, Bingong;Zheng, Zeqi;Li, Zhe
背景资料：糖尿病性心肌病（DCM）是糖尿病患者的一种心肌疾病，其特征是收缩和舒张功能障碍。方法：将大鼠分为3组，分别给予不同的治疗。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，糖尿病治疗组（n = 8）和糖尿病对照组（n = 8）分别给予重组人神经调节蛋白-1（rhNRG-1）治疗。所有研究均在诱导糖尿病后16周进行。行心导管检查以评价心功能。TUNEL染色检测凋亡细胞。左心室（LV）切片用Masson染色以研究心肌胶原含量。结果：糖尿病患者左室收缩压（LVSP）、左室压力最大上升速率（+dp/dt max）和最大下降速率（-dp/dt max）降低，左室舒张末期压（LVEDP）升高，心功能明显受损。rhNRG-1治疗可明显缓解上述症状，改善心功能。糖尿病组TUNEL染色阳性细胞数明显多于对照组，rhNRG-1治疗组凋亡细胞数明显减少。qRT-PCR结果显示，rhNRG-1可降低bax和caspase-3的表达，增加bcl-2的表达。胶原体积分数糖尿病组高于对照组。结论：rhNRG-1可明显改善DCM慢性心力衰竭大鼠的心功能，逆转心脏重构。这些结果支持应用rhNRG-1作为DCM治疗的可选治疗策略的临床可能性。
Background: 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.Methods: 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).Results: 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.Conclusion: 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.