养心定悸胶囊对糖尿病心肌病模型金黄地鼠的心肌保护作用  

Myocardial protective effect of Yangxin dingji capsule on diabetic cardiomyopathy model golden hamsters

作　　者：钟意 刘刚[2] 马国平[2] 丁宝珠 李晓霞 刘皓莹 梁文杰 ZHONG Yi;LIU Gang;MA Guoping;DING Baozhu;LI Xiaoxia;LIU Haoying;LIANG Wenjie(College of Integrated Chinese and Western Medicine,Hebei University of Chinese Medicine,Shijiazhuang 050200,China;First Dept.of Cardiology Medicine,the First Hospital Hebei Medical University,Shijiangzhuang 050000,China;Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation,Shijiazhuang 050200,China)

机构地区：[1]河北中医学院中西医结合学院,石家庄050200 [2]河北医科大学第一医院心内一科,石家庄050000 [3]河北省高校中药组方制剂应用技术研发中心,石家庄050200

出　　处：《中国药房》2022年第13期1573-1580,共8页China Pharmacy

基　　金：国家重点研发计划项目(No.2020YFC2004700);国家级大学生创新创业训练计划项目(No.202114432006);河北省重点研发计划项目(No.21377755D);河北省中医药管理局中医药类科研计划课题(No.2020149)。

摘　　要：目的探讨养心定悸胶囊对糖尿病心肌病(DCM)模型金黄地鼠心肌细胞的保护作用机制。方法将金黄地鼠分为对照组(10只,不造模、不给药)、模型组(9只,造模、不给药)、中药高剂量组[8只,造模、养心定悸胶囊给药2 g/(kg·d)]、中药低剂量组[8只,造模、养心定悸胶囊给药1 g/(kg·d)]、恩格列净组[9只,阳性对照,造模、给药10 mg/(kg·d)],所有金黄地鼠连续灌胃水或相应药物8周。实验期间观察金黄地鼠的一般情况,检测其血糖、总胆固醇(TC)、肌酸激酶同工酶MB(CK-MB)、左室射血分数(EF)、短轴缩短率(FS)和血清白细胞介素1β(IL-1β)、转化生长因子β1(TGF-β1)水平;观察金黄地鼠的心肌病理组织形态变化;检测并观察金黄地鼠心肌组织中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、天冬氨酸特异性半胱氨酸蛋白酶1(caspase-1)、消皮素D(GSDMD)、核转录因子κB(NF-κB)、IL-1β的mRNA及蛋白表达;检测心肌细胞DNA损伤情况。结果与对照组比较,模型组金黄地鼠血糖、TC、CK-MB水平,血清中IL-1β、TGF-β1水平,心肌组织中NLRP3、caspase-1、GSDMD、NF-κB、IL-1βmRNA表达水平、蛋白阳性表达及GSDMD蛋白表达水平均显著升高(P<0.05或P<0.01);EF、FS显著降低(P<0.01);心肌细胞结构不清,纤维排列紊乱,心肌间蓝染的胶原纤维增多;心肌组织DNA损伤阳性细胞显著增加。与模型组比较,各给药组以上指标均有不同程度逆转;心肌细胞间隙清晰,纤维排列紊乱得到改善;心肌组织DNA损伤阳性细胞均有不同程度减少。结论养心定悸胶囊可通过调控NLRP3/caspase-1/GSDMD信号通路抑制DCM模型金黄地鼠心肌细胞焦亡,减轻DCM炎症损伤,从而保护心肌细胞。OBJECTIVE To explore the protective mechanism of Yangxin dingji capsules on the cardiomyocytes of diabetic cardiomyopathy(DCM)model golden hamsters.METHODS In this study,golden hamsters were divided into control group(n=10,no modeling,no drug administration),model group(n=9,modeling,no drug administration),TCM high-dose group[n=8,modeling,Yangxin dingji capsules 2 g/(kg·d)],TCM low-dose group[n=8,modeling,Yangxin dingji capsules 1 g/(kg·d)]and empagliflozin group[n=9,positive control,modeling,10 mg/(kg·d)].All the golden hamsters were gavaged continuously for 8 weeks.The general conditions of golden hamsters were observed during the experiment.Blood glucose,total cholesterol(TC)and creatine kinase MB(CK-MB),ejection fraction(EF),fractional shortening(FS),interleukin 1β(IL-1β)and transforming growth factorβ1(TGF-β1)were detected;the histopathological changes of myocardium were observed.mRNA and protein expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,aspirin D(GSDMD),nuclear factorκB(NF-κB)and IL-1βwere detected and observed;DNA damage in myocardial was detected.RESULTS Compared with control group,the blood glucose,TC,CK-MB,serum IL-1β,TGF-β1 levels,the mRNA expressions and positive protein expression of NLRP3,caspase-1,GSDMD,NF-κB and IL-1βand protein expression of GSDMD in golden hamsters were significantly increased in model group(P<0.05 or P<0.01);EF and FS were significantly decreased(P<0.01);the fibers of myocardial cells was disordered,and the blue-stained collagen fibers between the myocardium increased;DNA damaged positive cells in myocardial tissue of gold hamsters increased significantly.Compared with model group,the above indexes of administration groups were reversed to varying degrees;the gap of myocardial cells were clear,and the fibers disorder was improved;the DNA damaged positive cells in the myocardial tissue were reduced to varying degrees.CONCLUSIONS Yangxin dingji capsule can inhibit the cardiomyocyte pyroptosis and relieve the inf

关 键 词：养心定悸胶囊 糖尿病心肌病 NLRP3/caspase-1/GSDMD信号通路 心肌细胞 

分 类 号：R965[医药卫生—药理学] R541.9[医药卫生—药学]