Toll样受体4通路参与高糖诱导的心房细胞纤维化  

TLR4 pathway is involved in hyperglycemia-induced fibrosis of atrial myocytes

作　　者：许爱青 陈红霞 王兴华[1] 张跃[1] 李广平[1] 富华颖[1] Xu Aiqing;Chen Hongxia;Wang Xinghua;Zhang Yue;Li Guangping;Fu Huaying(Department of Cardiology,Tianjin Medical University Second Hospital,Tianjin Key Laboratory of Ionic and Molecular Function in Cardiovascular Diseases,Tianjin Institute of Cardiology,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院心脏科,天津市心血管病离子与分子机能重点实验室,天津心脏病学研究所,300211

出　　处：《中华老年心脑血管病杂志》2021年第5期531-534,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：天津市自然科学基金(16JCYBJC25000);天津医科大学第二医院重点实验室科研基金(2018ZDSYS03);天津医科大学第二医院临床研究项目(2019LC03)。

摘　　要：目的探讨Toll样受体4(Toll-like receptor 4,TLR4)抑制剂TAK242对高糖引起的小鼠心房肌细胞纤维化蛋白表达的影响。方法高糖培养小鼠心房肌细胞系,实验细胞分为4组,对照组、对照抑制组、高糖对照组和高糖抑制组。观察TLR4、白细胞介素受体相关蛋白1(IRAK1)、NF-κB和Ⅰ型胶原A1表达水平,应用TLR4抑制剂TAK242抑制TLR4活性,观察IRAK1、NF-κB及Ⅰ型胶原A1表达。结果与对照组和对照抑制组比较,高糖对照组TLR4和IRAK1表达明显升高,差异有统计学意义(P<0.05);高糖抑制组IRAK1表达较高糖对照组有减低趋势,但差异无统计学意义(P>0.05)。高糖对照组NF-κB表达明显高于对照组和对照抑制组,且对照组NF-κB表达明显高于对照抑制组,差异有统计学意义(P<0.05);高糖抑制组NF-κB表达明显低于高糖对照组(1.52±0.08 vs 1.84±0.13,P<0.05)。与对照组和对照抑制组比较,高糖对照组Ⅰ型胶原A1表达明显升高;高糖抑制组Ⅰ型胶原A1表达明显低于高糖对照组(0.92±0.13 vs 1.36±0.12,P<0.05)。结论TLR4抑制剂能够下调高糖诱导的心房细胞纤维化蛋白。Objective To study the effect of TLR4 inhibitor TAK242 on hyperglycemia-induced fibrosis of atrial myocytes.Methods The mouse atrial myocytes cultured in a hyperglycemic medium were divided into control group,inhibitor control group,hyperglycemia group,hyperglycemia control group and hyperglycemia inhibition group.The expressions of TLR4,IL receptor-related protein(IRAK1),NF-κB and collagen typeⅠalpha 1 were detected.The activity of TLR4 was inhibited with its inhibitor TAK242.Results The expression levels of TLR4 and IRAK1 were significantly higher in hyperglycemia control group than in control group and inhibitor control group(P<0.05).The expression level of NF-κB was significantly higher in hyperglycemia control group than in control group and inhibitor control group and significantly lower in control group than in inhibitor control group(P<0.05)and in hyperglycemia inhibition group than in hyperglycemia control group(1.52±0.08 vs 1.84±0.13,P<0.05).The expression level of collagen typeⅠalpha 1 was significantly higher in hyperglycemia control group than in control group and inhibitor control group(P<0.05)and significantly lower in hyperglycemia inhibition group than in hyperglycemia control group(0.92±0.13 vs 1.36±0.12,P<0.05).Conclusion TAK242 can downregulate hyperglycemia-induced fibrosis of atrial myocytes.

关 键 词：TOLL样受体4 纤维化 糖尿病 NF-ΚB 胶原Ⅰ型 

分 类 号：R587.1[医药卫生—内分泌]