[1]曹露 刘鹏 张海明 李海宏 杨丽丽 马瑞芝 荣爱国.雷公藤红素通过调节TLR4/MyD88/NF-κB通路改善抵抗素诱导的H9c2心肌细胞肥大[J].心血管病学进展,2024,(12):1143.[doi:10.16806/j.cnki.issn.1004-3934.2024.12.019]
　CAO Lu,LIU Peng,ZHANG Haiming,et al.Celastrol Improves H9c2 Cardiomyocyte Hypertrophy Induced by Resistin by Regulating TLR4/MyD88/NF-B Pathway[J].Advances in Cardiovascular Diseases,2024,(12):1143.[doi:10.16806/j.cnki.issn.1004-3934.2024.12.019]
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雷公藤红素通过调节TLR4/MyD88/NF-κB通路改善抵抗素诱导的H9c2心肌细胞肥大()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年12期
页码:
1143
栏目:
论著
出版日期:
2024-12-25

文章信息/Info

Title:
Celastrol Improves H9c2 Cardiomyocyte Hypertrophy Induced by Resistin by Regulating TLR4/MyD88/NF-B Pathway
作者:
曹露1 刘鹏2 张海明1 李海宏3 杨丽丽1 马瑞芝1 荣爱国1
(1.山西省中西医结合医院检验科,山西 太原 030000;2.山西省心血管病医院心外科,山西太原 030000;3.山西省中西医结合医院输血科,山西 太原 030000)
Author(s):
CAO Lu1; LIU Peng2; ZHANG Haiming1; LI Haihong3; YANG Lili1; MA Ruizhi1; RONG Aiguo1
(1. Department of Laboratory Medicine, Shanxi Provincial Integrated TCM and WM Hospital,Taiyuan 030000,Shanxi,China;2. Department of Cardiac Surgery, Shanxi Cardiovascular Hospital,Taiyuan 030000,Shanxi,China;3. Department of Blood Transfusion, Shanxi Provincial Integrated TCM and WM Hospital,Taiyuan 030000,Shanxi,China)
关键词:
雷公藤红素; TLR4/MyD88/NF-κB通路; 抵抗素; 糖尿病心肌病; 心肌细胞肥大
Keywords:
Celastrol; TLR4/MyD88/NF-B pathway; Resistin; Diabetic cardiomyopathy; Cardiomyocyte hypertrophy
DOI:
10.16806/j.cnki.issn.1004-3934.2024.12.019
摘要:
目的 探究雷公藤红素通过调节Toll样受体4/髓样分化因子88/核因子-κB（TLR4/MyD88/NF-κB）通路对抵抗素（Resistin）诱导的H9c2心肌细胞肥大的影响。方法 ①H9c2细胞给予100 ng/mL抵抗素处理6 h、12 h、24 h、48 h、72 h，记作正常对照组（Control）、抵抗素6 h组（Resistin 6 h）、抵抗素12 h组（Resistin 12 h）、抵抗素24 h组（Resistin 24 h）、抵抗素48 h组（Resistin 48 h）、抵抗素72 h组（Resistin 72 h）。②H9c2细胞给予/不予TLR4基因干扰，并用抵抗素诱导48 h，记作抵抗素组（Resistin）、阴性对照组（Mock）和TLR4基因干扰组（si-TLR4）。③H9c2细胞给予雷公藤红素/TLR4通路抑制剂TAK-242处理，并用抵抗素诱导48 h，记作抵抗素组（Resistin）、雷公藤红素组（Celastrol）、TLR4抑制剂组（TAK-242）、雷公藤红素+TLR4抑制剂（TAK-242）组（Celastrol+TAK-242）。罗丹明-鬼笔环肽染色观察细胞肥大；流式细胞术检测细胞周期和细胞凋亡率；RT-qPCR检测细胞心肌肥厚标志物[心房利钠肽（ANP）、脑利钠肽（BNP）、β肌球蛋白重链（β-MHC）]mRNA水平；Western blotting检测细胞TLR4、MyD88、NF-κB p65、p-NF-κB p65蛋白水平。结果 ①与Control组比较，Resistin 24 h组、Resistin 48 h组、Resistin 72 h组细胞明显肥大，ANP、BNP、β-MHC mRNA水平升高， S期细胞比例降低，G0/G1期细胞比例、细胞凋亡率升高，TLR4、MyD88、p-NF-κB p65/NF-κB p65蛋白水平升高（均P<0.05）。②与Resistin组/Mock组比较，si-TLR4组细胞肥大明显改善，细胞ANP、BNP、β-MHC mRNA水平降低， S期细胞比例升高，G0/G1期细胞比例、细胞凋亡率降低，TLR4、MyD88、p-NF-κB p65/NF-κB p65蛋白水平降低（均P<0.05）。③与Resistin组比较，Celastrol组、TAK-242组、Celastrol+TAK-242组细胞肥大明显改善，细胞ANP、BNP、β-MHC mRNA水平降低， S期细胞比例升高，G0/G1期细胞比例、细胞凋亡率降低，TLR4、MyD88、p-NF-κB p65/NF-κB p65蛋白水平降低（P均<0.05）。结论 雷公藤红素通过调节TLR4/MyD88/NF-κB通路改善抵抗素诱导的H9c2心肌细胞肥大。
Abstract:
Objective To explore the effect of Celastrol on H9c2 cardiomyocyte hypertrophy induced by resistin by regulating the t oll like receptor 4/myeloid differentiation factor 88/nuclear factor-κB ( TLR4/MyD88/NF-κB) pathway. Methods ① H9c2 cells were treated with 100 ng/mL resistin for 6 h ,12 h,24 h,48 h,and 72 h,and designated as the normal control group (Control),resistin 6 h group (Resistin 6 h),resistin 12 h group (Resistin 12 h),resistin 24 h group (Resistin 24 h),resistin 48 h group (Resistin 48 h),and resistin 72 h group (Resistin 72 h). ② H9c2 cells were treated with/without TLR4 gene interference and induced with resistin for 48 h ,designated as resistin group (Resistin),negative control group (Mock),and TLR4 gene interference group (si-TLR4). ③ H9c2 cells were treated with Celastrol/TLR4 pathway inhibitor TAK-242 and induced with resistin for 48 h,designated as Resistin group,Celastrol group,TLR4 inhibitor group (TAK-242),Celastrol+TLR4 inhibitor group (Celastrol+TAK-242). Rhodamine-phalloidin staining was used to observe cell hypertrophy;Flow cytometry was used to detect cell cycle and apoptosis rate;RT-qPCR was used to detect cellular cardiac hypertrophy markers atrial natriuretic peptide (ANP) ,brain natriuretic peptide (BNP),and β-myosin heavy chain (β-MHC) mRNA levels ;Western blotting was used to detect TLR4,MyD88,NF-κB p65,and p-NF-κB p65 protein levels in cells. Results ① Compared with Control group ,cell in Resistin 24 h group,Resistin 48 h group,and Resistin 72 h group were significant hypertrophy,ANP,BNP,and β-MHC mRNA levels were increased,the proportion of S phase cells was decreased,while the proportion of G0/G1 phase cells and apoptosis rate were increased,TLR4,MyD88,p-NF-κB p65/NF-κB p65 protein levels were increased (all P<0.05). ② Compared with Resistin group/Mock group,cell hypertrophy in si-TLR4 group was significant improved,ANP,BNP,and β-MHC mRNA levels were decreased,the proportion of S phase cells was increased,while the proportion of G0/G1 phase cells and apoptosis rate were decreased,TLR4,MyD88,p-NF-κB p65/NF-κB p65 protein levels were decreased (all P<0.05). ③ Compared with Resistin group,cell hypertrophy in Celastrol group ,TAK-242 group,Celastrol+TAK-242 group were significant improved ,ANP,BNP,and β-MHC mRNA levels were decreased,the proportion of S phase cells were increased,while the proportion of G0/G1 phase cells and apoptosis rate were decreased,TLR4,MyD88,p-NF-κB p65/NF-κB p65 protein levels were decreased (all P<0.05). Conclusion Celastrol improved H9c2 cardiomyocyte hypertrophy induced by resistin by regulating TLR4/MyD88/NF-κB pathway.

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更新日期/Last Update: 2025-01-08