西南医科大学学报2024，Vol.47Issue(2)：136-140,5.DOI:10.3969/j.issn.2096-3351.2024.02.008
BKCa在高糖诱导的肾小球系膜细胞损伤中的作用及机制
The role and mechanism of BKCa in mesangial cell injury induced by high glucose
摘要
Abstract
Objective To explore the role and mechanism of BKCa(large conductance calcium-activated potassium channel,BKCa)in DN(diabetic nephropathy,DN).Methods ①After the intervention of agonist NS11021 and inhibitor Tet and BKCa-siRNA,the changes of cell proliferation rate,collagenⅣ(ColⅣ)and fibronectin(FN)in the DN cell model were observed to reveal the role of BKCa;②After the intervention of agonist NS11021 and inhibitor Tet and BKCa-siRNA on BKCa,the changes of TGF-β1(Transforming growth factor beta 1)and Smad2/3 were observed in DN cell model;After the intervention of agonist TGF-β1 and inhibitor SB431542 on TGF-β1/Smad2/3 signaling pathway,we observed the change of effects of BKCa on model cells,in order to reveal the correlation be-tween BKCa action and this signaling pathway.Results ①Compared with high glucose group,pharmacologically excited BKCa increased the proliferation rate of model cells,and the expression of BKCa β subunit protein was enhanced,the differences were statistically signifi-cant(P<0.05);compared with high glucose group,pharmacological and genetic inhibition of BKCa decreased the expression of α and β subunit protein,the proliferation rate of model cells decreased,and the secretion of ColⅣand FN decreased significantly(P<0.01).②Compared with the high glucose group,the content of Smad2/3 was increased due to the pharmacological excitation of BKCa,the con-tent of TGF-β1 and Smad2/3 was significantly decreased due to the pharmacological and gene inhibition of BKCa(the differences were statistically significant(P<0.05);compared with NS11021 group,after blocking TGF-β1/Smad2/3 signaling pathway with SB431542,the cell proliferation rate was significantly decreased,and the secretion of ColⅣand FN were decreased,and the differences were statis-tically significant(P<0.05).Conclusion BKCa was highly expressed in DN cell models induced by high glucose,and cell proliferation rate,ColⅣand FN secretion were significantly reduced after BKCa inhibition,thus improving DN lesions.This effect was related to TGF-β1/Smad2/3 signaling pathway.关键词
糖尿病肾病/大电导钙激活钾通道/胶原Ⅳ/纤连蛋白/TGF-β1/Smad2/3Key words
Diabetic nephropathy/BKCa/ColⅣ/FN/TGF-β1/Smad2/3分类
医药卫生引用本文复制引用
张雪,葛沛,顾立,李华,张丹,黄远琼,陈美娟..BKCa在高糖诱导的肾小球系膜细胞损伤中的作用及机制[J].西南医科大学学报,2024,47(2):136-140,5.基金项目
四川省科技厅基金项目(2023NSFSC0666) （2023NSFSC0666）
泸州市科技局-西南医科大学联合基金项目(2019LZXNYDJ50) （2019LZXNYDJ50）
西南医科大学-泸州市中医医院基地项目(2018-LH005) （2018-LH005）
