[1]黄娟,黄湘宁,王屹菲,等.左归降糖舒心方调控TLR4/NF-κB/NLRP3通路抑制H9C2心肌细胞炎性损伤机制[J].陕西中医,2025,46(11):1454-1461.[doi:DOI:10.3969/j.issn.1000-7369.2025.11.003]
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左归降糖舒心方调控TLR4/NF-κB/NLRP3通路抑制H9C2心肌细胞炎性损伤机制
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年11期
页码:
1454-1461
栏目:
基础研究
出版日期:
2025-11-05

文章信息/Info

作者:
黄娟1黄湘宁2王屹菲3李美英1刘晶晶1王瑾茜1刘林劵1林湘东1王婷婷1喻嵘2
(1.湖南中医药大学第一附属医院,湖南 长沙 410007;2.湖南中医药大学,湖南 长沙 410208;3.河南科技大学第一附属医院,河南 洛阳 471003)
关键词:
糖尿病心肌病左归降糖舒心方H9C2心肌细胞TLR4/NF-κB/NLRP3通路炎性损伤细胞焦亡
分类号:
R 541
DOI:
DOI:10.3969/j.issn.1000-7369.2025.11.003
文献标志码:
A
摘要:
目的:探讨左归降糖舒心方对于脂多糖(LPS)诱导的H9C2心肌细胞损伤的保护机制。方法:以H9C2心肌细胞为研究对象,随机分为空白血清组、模型组、左归降糖舒心方组、二甲双胍组、TAK-242组。除空白血清组外,其余各组均以LPS诱导损伤,构建心肌细胞炎症损伤体外模型。通过CCK-8法筛选含药血清干预浓度,ELISA法及免疫荧光法检测细胞IL-1β、TNF-α、IL-6含量及蛋白表达;Hoechst/PI双染检测细胞焦亡水平;AO/EB双染检测细胞膜通透性;Western Blot法检测TLR4、NF-κB p65、p-NF-κB p65及NLRP3蛋白表达;RT-PCR技术检测IL-1β、Caspase-1及GSDMD mRNA表达。结果:通过CCK-8法筛选,确定10%的左归降糖舒心方含药血清浓度为后续实验的干预浓度。与空白血清组相比,模型组H9C2细胞释放的TNF-α、IL-6、IL-1β含量和相对荧光强度增加(P<0.01)。PI染色细胞数量明显增多,EB橘红色荧光比例上升,TLR4、p-NF-κB p65、NLRP3蛋白表达升高,IL-1β、Caspase-1及GSDMD mRNA表达增高(均P<0.01)。与模型组相比,左归降糖舒心方组、二甲双胍组、TAK-242组细胞中的TNF-α、IL-6、IL-1β含量及相对荧光强度降低(P<0.01)。PI染色细胞数量减少,左归降糖舒心方组AO/EB染色的EB橘红色荧光比例缩小。中药含药血清及TAK-242可抑制细胞的TLR4、p-NF-κB p65、NLRP3蛋白表达和Caspase-1、GSDMD mRNA表达。结论:左归降糖舒心方含药血清能抑制LPS诱导的H9C2心肌细胞炎症反应,减轻心肌细胞焦亡,这与抑制TLR4/NF-κB/NLRP3信号通路相关。

参考文献/References:

[1]KIM A H,JANG J E,HAN J.Current status on the therapeutic strategies for heart failure and diabetic cardiomyopathy[J].Biomedicine & Pharmacotherapy,2022,145:112463.
[2]李双娣,王鑫焱,邓悦.从毒损心络理论探讨糖尿病心肌病发病机制及相关研究[J].中国中医药现代远程教育,2016,14(3):43-45.
[3]彭少林,何绪屏,汪栋材,等.健心平律丸治疗糖尿病心肌病心功能不全临床观察[J].中医药临床杂志,2020,32(6):1116-1119.
[4]李莺莺,王欣,王芙蓉.生脉散治疗糖尿病心肌病探析[J].世界科学技术-中医药现代化,2022,24(4):1509-1514.
[5]苏丽清,喻嵘,吴勇军,等.左归降糖舒心方对糖尿病心肌病MKR鼠心肌细胞损伤和凋亡的影响[J].世界科学技术-中医药现代化,2022,24(2):554-562.
[6]田娜,喻嵘,张薇薇,等.左归降糖舒心方调控自噬对糖尿病转基因MKR鼠心肌损伤的影响[J].中国中医基础医学杂志,2023,29(5):747-752.
[7]廖心悦,向琴,邹骏驹,等.左归降糖舒心方对糖尿病心肌病MKR鼠Foxo1/β-MHC的影响[J].时珍国医国药,2023,34(6):1302-1305.
[8]JIA G,WHALEY-CONNELL A,SOWERS J R.Diabetic cardiomyopathy:A hyperglycaemia and insulin resistance induced heart disease[J].Diabetologia,2018,61(1):21-28.
[9]TAN Y,ZHANG Z,ZHENG C,et al.Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies:Preclinical and clinical evidence[J].Nature Reviews Cardiology,2020,17(9):585-607.
[10]RITCHIE R H,ABEL E D.Basic mechanisms of diabetic heart disease[J].Circulation Research,2020,126(11):1501-1525.
[11]杨洛琦,谢连娣,周莉君.从藏象理论探析糖尿病心肌病[J].陕西中医,2022,43(10):1423-1426.
[12]YOUSSEF M E,ABDELRAZEK H M,MOUSTAFA Y M.Cardioprotective role of GTS-21 by attenuating the TLR4/NF-κB pathway in streptozotocin-induced diabetic cardiomyopathy in rats[J].Naunyn-Schmiedeberg’s Archives of Pharmacology,2021,394(1):11-31.
[13]SUN Y,DING S.NLRP3 inflammasome in diabetic cardiomyopathy and exercise intervention[J].International Journal of Molecular Sciences,2021,22(24):13228.
[14]黄娟,王一阳,肖凡,等.左归降糖舒心方调控TLR4/NF-κB通路抑制糖尿病心肌病小鼠心肌纤维化的机制研究[J].湖南中医药大学学报,2024,44(5):729-736.
[15]易建华,李雯.脂多糖诱导的急性炎症小鼠模型血清促炎因子与抑炎因子表达研究[J].陕西医学杂志,2023,52(4):395-398,403.
[16]MOHR A E,CRAWFORD M,JASBI P,et al.Lipopolysaccharide and the gut microbiota:Considering structural variation[J].FEBS Letters,2022,596(7):849-875.
[17]QIU Z,HE Y,MING H,et al.Lipopolysaccharide aggravates high glucose-and Hypoxia/Reoxygenation-induced injury through activating ROS-dependent NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes[J].Journal of Diabetes Research,2019:8151836.
[18]FRANTZ S,KOBZIK L,KIM Y D,et al.Toll4 expression in cardiac myocytes in normal and failing myocardium[J].Journal of Clinical Investigation,1999,104(3):271-280.
[19]SHI H,ZHOU P,NI Y Q,et al.In vivo and in vitro studies of Danzhi Jiangtang capsules against diabetic cardiomyopathy via TLR4/MyD88/NF-κB signaling pathway[J].Saudi Pharmaceutical Journal:SPJ,2021,29(12):1432-1440.
[20]SANGWENI N F,MOSA R A,DLUDLA P V,et al.The triterpene methyl-3β-hydroxylanosta-9,24-dien-21-oate attenuates high glucose-induced oxidative damage and apoptosis by improving energy metabolism[J].Phytomedicine:International Journal of Phytotherapy and Phytopharmacology,2021,85:153546.
[21]SWIATKIEWICZ I,PATEL N T,VILLARREAL-GONZALEZ M,et al.Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center[J].BMC Medicine,2024,22(1):195.
[22]ZHANG L,AI C,BAI M,et al.NLRP3 Inflammasome/Pyroptosis:A key driving force in diabetic cardiomyopathy[J].International Journal of Molecular Sciences,2022,23(18):10632.
[23]CHEN J,LAI J,YANG L,et al.Trimetazidine prevents macrophage-mediated septic myocardial dysfunction via activation of the histone deacetylase sirtuin 1[J].British Journal of Pharmacology,2016,173(3):545-561.
[24]SUN S,GONG D,LIU R,et al.Puerarin inhibits NLRP3-Caspase-1-GSDMD-mediated pyroptosis via P2X7 receptor in cardiomyocytes and macrophages[J].International Journal of Molecular Sciences,2023,24(17):13169.
[25]黄芷棋,宁一博,贺润铖,等.NLRP3炎性小体与糖尿病心肌病的发生发展[J].中国药理学通报,2021,37(4):463-467.
[26]沈玉珏.黄芪多糖抑制缺氧/复氧损伤乳鼠心肌细胞凋亡与自噬机制研究[J].陕西中医,2021,42(5):561-564.
[27]李晨,梁凡,胡明旭,等.基于PI3K通路探讨参芪苈心方对心肌细胞的保护作用[J].陕西中医,2025,46(3):291-295.

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备注/Memo

备注/Memo:
国家自然科学基金资助面上项目(U21A20411,82074400);湖南省自然科学医卫行业联合基金资助项目(2024JJ9436);湖南省教育厅重点项目(24A0272);湖南省卫生健康委员会科研基金资助项目(W20243161);湖南省教育厅优秀青年项目(24B0376);湖南省自然科学基金资助项目(2024JJ9440);湖南中医药大学校院联合基金资助项目(2024XYLH033)
更新日期/Last Update: 2025-11-04