白虎人参汤合枳实薤白桂枝汤对糖尿病心肌病MKR小鼠心肌细胞焦亡的影响  

Effects of Baihu Renshen Decoction combined with Zhishi Xiebai Guizhi Decoction on myocardial pyroptosis in MKR diabetic cardiomyopathy mice

作　　者：史留阳 谭丹妮 刘秀[1] 向琴[1] 谭艳 喻嵘[1] SHI Liuyang;TAN Danni;LIU Xiu;XIANG Qin;TAN Yan;YU Rong(Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《湖南中医药大学学报》2023年第4期591-597,共7页Journal of Hunan University of Chinese Medicine

基　　金：国家自然科学基金项目(82074400,U21A20411,82004185);湖南省教育厅创新平台开放基金项目(20K094);湖南省教育厅科技计划青年项目(20B450);湖南省科学厅重点研发计划项目(2020SK2101)。

摘　　要：目的探究白虎人参汤合枳实薤白桂枝汤对糖尿病心肌病模型MKR小鼠心肌细胞焦亡相关蛋白表达的影响。方法造模成功后将MKR小鼠随机分成模型组,中药低、中、高剂量组,二甲双胍组,同时设FVB鼠为正常组。给药4周后观察小鼠糖脂代谢变化;超声成像平台检测小鼠心功能;HE染色及MASSON染色观察心肌组织形态;ELISA法测定血清中白细胞介素-18(interleukin-18,IL-18)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;Western blot法检测小鼠心肌组织NOD样受体蛋白3(nucleotidebinding oligomerization domain-like receptors 3,NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein contain a CARD,ASC)、半胱氨酸的天冬氨酸蛋白水解酶-1(cysteinyl aspartate specific proteinase-1,Caspase-1)蛋白水平。结果与正常组比较,模型组小鼠空腹血糖(fasting blood glucose,FBG)显著升高(P<0.01),血清总胆固醇(serum total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein,LDL)水平升高(P<0.05),高密度脂蛋白胆固醇(high density liptein cholesterol,HDL-C)水平降低(P<0.05),左室射血分数(rejection fraction,EF)、左室短轴缩短率(fractional shortening,FS)数值明显降低(P<0.01);细胞肥大变形,心肌纤维排列紊乱,纹理不齐,血清IL-1β、IL-18、TNF-α含量升高(P<0.01),心肌组织IL-1β、IL-18、TNF-α蛋白表达水平提升(P<0.01),心肌组织NLRP3、ASC、Caspase-1蛋白表达均显著增高(P<0.01)。与模型组比较,各用药组小鼠FBG、TC、TG、LDL水平降低(P<0.05),HDL-C水平升高(P<0.05),EF、FS值均有升高(P<0.05),小鼠心肌组织病理学损伤明显改善,血清IL-1β、IL-18、TNF-α含量降低(P<0.05),NLRP3、ASC、Caspase-1蛋白表达均明显降低(P<0.05),其中中药高剂量组作用最为明显。结论白虎人参汤合枳实薤白桂枝汤对心肌有保护作用,其机制可能与抑制NLRP3炎症小体Objective To investigate the effects of Baihu Renshen Decoction combined with Zhishi Xiebai Guizhi Decoction on the expression of pyroptosis-related protein in myocardial cells of MKR diabetic cardiomyopathy model mice.Methods After successful modeling,MKR mice were randomly divided into model group,low-,medium-and high-dose of Chinese medicine group,and metformin group.FVB mice were set as normal group.After 4 weeks of administration,the changes of glucose and lipid metabolism in mice were observed;the cardiac function of mice was checked by ultrasound imaging platform;the myocardial histomorphology was observed by HE staining and MASSON staining;the serum levels of interleukin-18(IL-18),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)were measured by ELISA;the nucleotidebinding oligomerization domain-like receptor 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),and cysteinyl aspartate specific proteinase-1(Caspase-1)protein levels in mouse myocardial tissue were measured by Western blot.Results Compared with the normal group,fasting blood glucose(FBG)was significantly higher(P<0.01),serum total cholesterol(TC),triglyceride(TG)and low density lipoprotein(LDL)levels increased(P<0.05),while high density lipoprotein cholesterol(HDL-C)levels decreased(P<0.05),left ventricular ejection fraction(EF)and left ventricular fractional shortening(FS)values were significantly reduceed(P<0.01)in the model group;cell hypertrophy and deformation,myocardial fibers were disorganized,texture was irregular,serum IL-1β,IL-18 and TNF-α content increased,IL-1β,IL-18 and TNF-α protein expression levels in myocardial tissue increased,and NLRP3,ASC and Caspase-1 protein expression in myocardial tissue were significantly elevated(P<0.01).Compared with the model group,in each treatment group,FBG,TC,TG and LDL levels decreased(P<0.05),HDL-C level was higher(P<0.05),EF and FS values increased(P<0.05),myocardial histopathological damage was significantly alleviated,serum IL-1β,IL-18 and TNF-α content

关 键 词：糖尿病心肌病 白虎人参汤合枳实薤白桂枝汤 NOD样受体蛋白3炎性小体 炎症 细胞焦亡 

分 类 号：R285.5[医药卫生—中药学]