甲异靛对1型糖尿病大鼠心肌损伤的修复作用  

Repair effect of meisoindigo on myocardial damage in type 1 diabetes mellitus in rats

作　　者：刘晶晶[1,2,3,4] 牟艳玲[2,3,4] 

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,山东济南250200 [2]山东省医学科学院药物研究所 [3]国家卫生部生物技术药物重点实验室 [4]山东省罕少见病重点实验室,山东济南250062

出　　处：《中国药理学通报》2018年第1期123-128,共6页Chinese Pharmacological Bulletin

基　　金：山东省自主创新及成果转化专项(No 2014ZZCX02105);山东省医学科学院医药卫生科技创新工程

摘　　要：目的观察甲异靛对糖尿病大鼠Wnt/β-catenin信号通路中相关蛋白在1型糖尿病大鼠心肌中表达的影响,明确其在糖尿病心肌病发生、发展中的作用。方法 SD♂大鼠腹腔一次性注射链脲佐菌素建立1型糖尿病大鼠模型,取模型成功大鼠分为糖尿病4、8周模型组以及甲异靛4、8周给药组。尾静脉采血检测空腹血糖值;HE染色法观察心肌病理结构变化;Western blot和免疫组织化学法检测心肌GSK-3β、p-GSK-3β、Wnt2、β-catenin、NF-κB-p65、p-NF-κB-p65蛋白表达变化。结果与正常对照组比较,1型糖尿病大鼠血糖值明显升高,体质量明显下降(P<0.01),8周甲异靛给药组大鼠血糖与糖尿病组比较明显下降(P<0.01);显微镜下能观察到糖尿病模型组大鼠心肌不同程度局灶性心肌细胞肥大、溶解性坏死、纤维组织增生等,甲异靛给药组大鼠心肌病变较糖尿病模型组有不同程度的缓解。糖尿病模型大鼠相对于正常对照组,心肌p-GSK-3β、Wnt2、β-catenin、p-NF-κB-p65表达升高,尤其是8周时,差异有显著性(P<0.01),给药组的蛋白表达与DM模型组比较明显降低(P<0.01)。结论甲异靛可能是通过降低Wnt2、β-catenin、GSK-3β等蛋白的表达,从而抑制Wnt/β-catenin信号通路在糖尿病大鼠体内的激活,参与修复糖尿病大鼠的心肌损伤及炎症过程,进一步研究该药在糖尿病大鼠心肌损伤修复中的作用机制,将为糖尿病心肌病找到新的治疗靶点提供理论依据。Aim To observe the influence of meisoindigo on the alteration of Wnt/β-catenin signaling in type 1 diabetic rats' myocardium and clarify its role in the development of diabetic cardiomyopathy. Methods The type 1 diabetes rat model was established by injection of streptozocin after one-week adaptive feeding.The successful modeling rats were randomly divided into DM model group of 4 weeks and 8 weeks,meisoindigo group of 4 weeks and 8 weeks. Fasting blood glucose( FBG) levels were tested. HE staining was used to observe the pathological changes of myocardial structures. The alteration of GSK-3β,p-GSK-3β,Wnt2,β-catenin,NF-κB-p65,p-NF-κB-p65 in myocardium was determined by Western blot and immunohistochemistry. Results Compared with control group,FBG levels of type 1 diabetic rats significantly increased( P< 0. 01),while body weight levels significantly decreased( P < 0. 01); compared with DM group,FBG levels of 8 weeks meisoindigo group significantly decreased( P < 0. 01). Myocardial histological analysis revealed that DM induced myocardial focal myocyte hypertrophy,solubility,necrosis,fiber tissue hyperplasia; compared with DM group,these symptoms were eased in meisoindigo group of 4 weeks and 8 weeks.Compared with control group,the expression of p-GSK-3β,Wnt2,β-catenin,p-NF-κB-p65 level increased,especially with DM group of 8 weeks( P < 0. 01). The expression of p-GSK-3β,Wnt2,β-catenin,p-NF-κBp65 level in meisoindigo group of 4 weeks and 8 weeks decreased significantly( P < 0. 01). Conclusions The repair effect of meisoindigo on myocardial damage in type 1 diabetic rats may be caused by lowering the expression of proteins in Wnt/β-catenin signaling and inhibiting the activation of Wnt/β-catenin signaling pathway,participating in the repair of myocardial damage and inflammatory in diabetic rats. Further researches on its mechanism in repairing diabetic myocardial damage may find new therapeutic targets for diabetic cardiomyopathy.

关 键 词：1型糖尿病 糖尿病心肌病 甲异靛 GSK-3Β Wnt2 Β-CATENIN 

分 类 号：R-332[医药卫生] R322.11