基于“络脉”理论的通心络胶囊对糖尿病大鼠心肌TGF-β1-p38MAPK-CREB信号通路的影响  

The effect of Tongxinluo capsule based on"choroid"theory on TGF-β1-p38MAPK-CREB signaling pathway in diabetic rats

作　　者：张常喜 张亚平 张晓晋 张雄慧 闫文瑞 马力 ZHANG Chang-Xi;ZHANG Ya-Ping;ZHANG Xiao-Jin(Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine Department of Pulmonary Diseases,Yinchuan 750021,Ningxia,China)

机构地区：[1]宁夏回族自治区中医医院暨中医研究院肺病科,宁夏银川750021 [2]庆阳市中医医院肺病科 [3]宁夏医科大学中医学院

出　　处：《中国老年学杂志》2025年第2期340-344,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81960810)。

摘　　要：目的探讨通心络胶囊对于糖尿病大鼠心肌损伤的作用及可能机制。方法将SPF级健康雄性SD大鼠随机分为正常对照组(n=8)和模型组(n=40)。模型组采用高脂饲料及尾静脉注射链脲佐菌素建立糖尿病大鼠模型,成功后,随机分为糖尿病组、通心络高、中、低剂量组、缬沙坦组,每组8只。通心络胶囊低、中、高剂量组按照0.25、0.50、1.00 kg/(kg·d)灌胃,缬沙坦组按30 mg/(kg·d)给药,每日1次,连续给药10 w。对照组及糖尿病组灌胃生理盐水,定期测定各组血糖、体质量,测定心脏质量,计算心脏质量指数,采用苏木素-伊红(HE)、马松(Masson)染色法观察心肌组织病理变化;酶联免疫吸附试验(ELISA)检测转化生长因子(TGF)-β1、B细胞淋巴瘤(Bcl)-2、胱天蛋白酶(Caspase)-3蛋白水平,Western印迹法检测TGF-β1、磷酸化(p)-p38丝裂原活化蛋白激酶(MAPK)、p-环磷腺苷效应元件结合蛋白(CREB)的蛋白表达情况。结果与对照组相比,糖尿病组血糖显著升高,体质量增加缓慢,心功能减退,心肌纤维肥大、排列紊乱,并可见明显胶原组织沉积,心肌组织中TGF-β1、p-p38MAPK、Caspase-3表达上调,Bcl-2、p-CREB蛋白水平降低,差异显著(P<0.05)。与糖尿病组比较,缬沙坦组、通心络中、高剂量组病理改变相对减少,心功能改善,心肌组织中TGF-β1、p-p38MAPK、Caspase-3表达下调,Bcl-2、p-CREB蛋白水平升高,差异显著(P<0.05)。结论通心络胶囊可延缓糖尿病大鼠心肌损伤,其作用机制可能与激活TGF-β1-p38MAPK-CREB信号通路有关。Objective To investigate the effect and possible mechanism of Tongxinluo capsule on myocardial injury in diabetic rats.Methods SPF healthy male SD rats were randomly divided into normal control group(n=8)and model group(n=40).The model(diabetic rats model)group was established with high-fat diet and streptozotocin injected into tail vein,after success,the rats were randomly divided into diabetic group,Tongxinluo high,medium and low dose groups,and valsartan group,with 8 rats in each group.Tongxinluo capsule low,medium and high dose groups were administrated orally by 0.25,0.50 and 1.00 kg/(kg·d),while valsartan group was administrated by 30 mg/(kg·d),once a day for 10 w.The control group and the diabetic group were given normal saline,blood glucose and body mass of each group were measured regularly,the heart mass was determined,and the heart mass index was calculated.Hematoxyn-eosin(HE)and Masson staining were used to observe the pathological changes of myocardial tissue.The protein levels of transforming growth factor(TGF)-β1,B cell lymphoma(Bcl)-2 and Caspase-3 were detected by enzyme-linked immunosorbent assay(ELISA).The protein expressions of TGF-β1,phosphorylated(p)-p38 mitogen activated protein kinase(MAPK)and p-cyclic adenosine effector element-binding protein(CREB)were detected by Western blot.Results Compared with the control group,the blood glucose was significantly increased,the body mass was slowly increased,the cardiac function was decreased,the myocardial fibers were enlarged,the arrangement was disordered,and the collagen tissue was obviously deposited,the expressions of TGF-β1,pp38MAPK and Caspase-3 were up-regulated,and the levels of Bcl-2 and p-CREB protein were decreased in myocardium of the diabetic group,the difference was significant(P<0.05).Compared with the diabetic group,the pathological changes were relatively reduced,cardiac function was improved,the expressions of TGF-β1,p-p38MAPK,Caspase-3 were down-regulated,the levels of Bcl-2 and p-CREB protein were increased in myocardium o

关 键 词：通心络胶囊 糖尿病心肌病 转化生长因子-β1 P38丝裂原活化蛋白激酶 环磷腺苷效应元件结合蛋白 

分 类 号：R587.1[医药卫生—内分泌]