miR-199b-5p在糖尿病肾病大鼠肾脏纤维化中作用机制  

Mechanism of miR-199b-5p onrenal fibrosis in diabetes nephropathy rats

作　　者：张冬[1] 李宗英 高原[1] 肖娜[1] ZHANG Dong;LI Zongying;GAO Yuan;XIAO Na(Department of Nephrology,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]沧州市中心医院肾内一科,河北沧州061000

出　　处：《生物技术》2024年第2期227-231,260,共6页Biotechnology

基　　金：沧州市重点研发计划指导项目(213106065)。

摘　　要：[目的]探索miR-199b-5p在糖尿病肾病大鼠肾脏纤维化中的作用机制。[方法]选择92只雄性大鼠,随机分为空白对照组、DN组、慢病毒对照组、miR-199b-5p敲低组,造模结束后第12 w处死大鼠。对比上述4组大鼠在肾组织病理学、肾功能指标,Klotho、Wnt、β-catenin等相关蛋白表达差异。[结果] DN组、慢病毒对照组的miR-199b-5p表达高于空白对照组和miR-199b-5p敲低组,miR-199b-5p敲低组高于空白对照组(1.08±0.24、3.27±0.12、3.22±0.53、1.62±0.15;P<0.05);DN组、慢病毒对照组的Scr、BUN、β-catenin、α-SMA、MMP-7均显著高于空白对照组和miR-199b-5p敲低组,miR-199b-5p敲低组高于空白对照组(78.66±2.12 vs 61.14±3.78;14.04±1.09 vs 9.26±1.73;32.33±2.57 vs 27.23±1.78;0.97±0.02 vs 0.34±0.35;3.49±0.28 vs 1.43±0.23;P<0.05);而DN组、慢病毒对照组的Klotho明显低于空白对照组和miR-199b-5p敲低组,miR-199b-5p敲低组低于空白对照组(23.18±3.12 vs 31.99±3.09;P<0.05)。[结论]降低miR-199b-5p表达可以上调糖尿病肾纤维化Klotho表达,抑制Wnt/β-catenin信号通路从而让α-SMA和MMP-7表达下降,进而延缓肾脏纤维化,改善肾功能指标,因此该通路可能是临床上治疗糖尿病肾纤维化的新靶点。[Objective]To explore the mechanism of miR-199b-5p in renal fibrosis of diabetes nephropathy rats.[Method]Eighty male rats were randomly divided into blank control group,DN group,lentivirus control group and miR-199b-5p knockdown group.The rats were sacrificed at 12 weeks after miR-199b-5p modeling.The differences in renal histopathology,renal function indexes,Klotho,Wnt,β-catenin and other related protein expression were compared among the above four groups.[Result]The expression of miR-199b-5p in DN group and lentiviral control group was higher than that in blank control group and miR-199b-5p knockdown group,and that in miR-199b-5p knockdown group was higher than that in blank control group(1.08±0.24,3.27±0.12,3.22±0.53,1.62±0.15;P<0.05);The levels of Scr,BUN,β-catenin,α-SMA,MMP-7 in miR-199b-5p knockdown group were significantly higher than those in blank control group and miR-199b-5p knockdown group(78.66±2.12 us 61.14±3.78;14.04±1.09 us 9.26±1.73;32.33±2.57 us 27.23±1.78;0.97±0.02 us 0.34±0.35;3.49±0.28 us 1.43±0.23;P<0.05);However,Klotho in DN group and lentiviral control group was significantly lower than that in blank control group and miR-199b-5p knockdown group,and that in miR-199b-5p knockdown group was lower than that in blank control group(23.18±3.12 us 31.99±3.09;P<0.05).[Conclusion]Decreasing miR-199b-5p expression can up regulate Klotho expression and inhibit Wnt/β-Catenin signaling pathway in diabetes rats with renal fibrosis.The decreased expression ofα-SMA and MMP-7 can delay renal fibrosis and improve renal function indicators,so this pathway may be a new target for the treatment of diabetic renal fibrosis in clinic.

关 键 词：糖尿病肾病 肾脏 纤维化 大鼠 miR-199b-5p KLOTHO WNT Β-CATENIN 

分 类 号：R589.9[医药卫生—内分泌]