[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。09vs9。26±1。73;32。33±2。57 vs 27。23±1。78;0。97±0。02vs0。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。
Mechanism of miR-199b-5p on renal fibrosis in diabetes nephropathy rats
[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 con-trol 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,a-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 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);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 vs 31.99±3.09;P＜0.05).[Conclusion]De-creasing miR-199b-5p expression can up regulate Klotho expression and inhibit Wnt/β-Catenin signaling pathway in dia-betes rats with renal fibrosis.The decreased expression of a-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.
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