姜黄素改善糖尿病心肌病大鼠心室重构及机制的研究

Effects of Curcumin on Ventricular Remodeling in Diabetic Cardiomyopathy Rats and Its Mechanism

目的探索姜黄素对糖尿病心肌病(DCM)大鼠血糖及抑制心室重构的影响。方法雄性Wistar大鼠40只,适应性喂养1周后,随机分为对照组(n=10)、模型组(n=10)、姜黄素组(n=10)和阳性对照组(n=10)。采用高脂高热量饮食+单次40mg/kg链脲佐菌素腹腔注射建立DCM动物模型,姜黄素组大鼠给予姜黄素注射液30mg/(kg·d)腹腔注射;阳性对照组大鼠给予40mg/(kg·d)柚皮苷灌胃,对照组及模型组大鼠腹腔注射等量6%乙醇和6%聚乙二醇混合液,各组大鼠连续用药8周。检测各组大鼠给药前后血糖变化;给药8周后行高频超声心动图检查,测定各项心功能指标;处死大鼠,取心脏,行HE、Masson染色进行心肌组织胶原容积分数分析。TUNEL法检测各组大鼠心肌细胞凋亡;ELISA法检测各组大鼠心室肌中基质金属蛋白酶(MMP)-9及MMP-2表达,并用HemI软件进行热图分析;Western blot检测各组大鼠心肌组织中GRP78、IRE1、JNK及p-JNK表达。结果与模型组相比,姜黄素组大鼠给药8周后血糖明显降低(P<0.05),心脏彩超结果显示左室重构各项指标均有明显改善(P<0.05);姜黄素组大鼠心肌纤维化病理积分及纤维化相关因子MMP-9及MMP-2表达明显下降(P<0.05);姜黄素组大鼠心肌组织GRP78、IRE1、JNK及p-JNK表达及细胞凋亡明显减少(P<0.05)。结论姜黄素可以通过降低DCM大鼠血糖、减轻心肌纤维化、抗心肌细胞凋亡等多个方面起到抑制DCM大鼠心室重构的作用。

Objective To explore the effects of curcumin on blood glucose and ventricular remodeling in diabetic cardiomyopathy rats（DCM）.Methods Forty male wistar rats were randomly divided into control group（n =10）,model group（n =10）,curcumin group（n =10）,and positive control group（n =10）after one week of adaptive feeding.The high-fat high-calorie diet plus single chain of 40 mg/kg streptozotocin with intraperitoneal injection were used to establish animal model of DCM,rats in curcumin group and positive control group rats were given intragastric administration of 40 mg/（kg·d）naringin;6%ethanol and 6% polyethylene glycol mixture rats in control group and model group intraperitoneal,administrated 8 weeks.Rats in each group were measured for blood glucose changes before and after drug administration;after 8 weeks of administration,the heart function indexes were measured by high frequency echocardiography;then the rats were sacrificed.The myocardial tissue was taken for HE staining,Masson for collagen volume fraction analysis.Apoptosis of myocardial cell were detected by TUNEL.The expressions of matrix metalloproteinase（MMP）-9 and MMP-2 were detected by ELISA in myocardium of rats,and image analysis by HemI software.The expression of GRP78,IRE1,JNK and p-JNK in rat myocardium were detected by western blot.Results Compared with the model group,the rats in curcumin group after 8 weeks of administration,the blood glucose decreased significantly（P〉0.05）.The echocardiography showed that left ventricular remodeling indicators were significantly improved（P〈0.05）.The myocardial fibrosis integral and MMP-9 and MMP-2 expressions were significantly decreased in curcumin group（P〈0.05）.The expressions of GRP78,IRE1,JNK,p-JNK and cell apoptosis were significantly reduced in myocardial tissue of the rats in curcumin group（P〈0.05）.Conclusion Curcumin can decrease the blood glucose of DCM rats,reduce myocardial fibrosis,anti-myocardial cell apoptosis,inhibit ventricular remodeling in DCM rats.