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
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篇名: 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
TITLE: Myocardial protective effect of Yangxin dingji capsule on diabetic cardiomyopathy model golden hamsters
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2g/(kg·d)]、中药低剂量组[8只,造模、养心定悸胶囊给药1g/(kg·d)]、恩格列净组[9只,阳性对照,造模、给药10mg/(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。
ABSTRACT: OBJECTIVE To explore t he 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 factor β1(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 factor κB (NF-κB)and IL- 1β were 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 NLRP 3,caspase-1,GSDMD,NF-κ B and IL-1 β and 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 tiss ue 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 inflammatory injury of DCM in DCM model golden hamsters by regulating the NLRP 3/caspase-1/GSDMD signaling pathway ,so as to protect the cardiomyocytes.
期刊: 2022年第33卷第13期
作者: 钟意,刘刚,马国平,丁宝珠,李晓霞,刘皓莹,梁文杰
AUTHORS: ZHONG Yi,LIU Gang,MA Guoping ,DING Baozhu ,LI Xiaoxia ,LIU Haoying ,LIANG Wenjie
关键字: 养心定悸胶囊;糖尿病心肌病;NLRP3/caspase-1/GSDMD信号通路;心肌细胞
KEYWORDS: Yangxin dingji capsule ;diabetic cardiomyopat hy;NLRP3/caspase-1/GSDMD signaling pathway ;cardiomyocyte
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