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史留阳,谭丹妮,刘秀,向琴,谭艳,喻嵘.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[J].湖南中医药大学学报英文版,2023,43(4):591-597.[Click to copy
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| 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 |
| 史留阳,谭丹妮,刘秀,向琴,谭艳,喻嵘 |
| (湖南中医药大学, 湖南 长沙 410208) |
| 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炎症小体过度激活，减少心肌细胞焦亡，降低炎症反应有关。 |
| 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 |
| DOI：10.3969/j.issn.1674-070X.2023.04.003 |
| Received:November 01, 2022 |
| 基金项目: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）；湖南省科学厅重点研发计划项目（2020SK2101）；湖南省教育厅科技计划青年项目（20B450）。 |
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| Effects of Baihu Renshen Decoction combined with Zhishi Xiebai Guizhi Decoction on myocardial pyroptosis in MKR diabetic cardiomyopathy mice |
| SHI Liuyang,TAN Danni,LIU Xiu,XIANG Qin,TAN Yan,YU Rong |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| 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 decreased (P<0.05), and NLRP3, ASC and caspase-1 protein expressions significantly decreased (P<0.05), with the most significant effect in the high dose group of Chinese medicine.Conclusion Baihu Renshen Decoction combined with Zhishi Xiebai Guizhi Decoction has protective effects on myocardium, and the mechanism may be related to the inhibition of NLRP3 inflammasome overactivation, the reduction of myocardial cell pyroptosis, and the reduction of inflammatory response. |
| Key words: diabetic cardiomyopathy Baihu Renshen Decoction combined with Zhishi Xiebai Guizhi NOD-like receptor protein 3 inflammasome inflammation pyroptosis |
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