申永超 林佳 冯琪 朱大荣

[摘要] 目的 探讨miR-92b与信号通路PI3K/Akt在糖尿病肾病中的相关性。 方法 选取8周龄的C57BL/6 雄性小鼠12只，随机分为正常对照组和糖尿病肾病组，利用枸橼酸钠建立糖尿病肾病小鼠模型;选取人肾小管上皮HK-2细胞12瓶，随机分为高糖组、低糖组和左旋葡萄糖组，用高糖刺激建立糖尿病肾病细胞模型。利用实时荧光定量PCR检测小鼠肾脏组织和细胞中miR-92b表达水平，Western blot检测小鼠肾脏组织和细胞中Akt和P-Akt的表达水平。 结果 糖尿病肾病组和高糖组miR-92b表达水平明显低于对照组（P<0.05），而P-Akt/Akt表达水平明显高于对照组（P<0.05）。将信号通路PI3K/Akt抑制剂LY294002加入到高糖诱导的糖尿病肾病细胞模型中，信号通路PI3K/Akt被抑制的同时，miR-92b表达显著升高（P<0.05）。结论 糖尿病肾病时，miR-92b与PI3K/Akt的表达呈负相关。

[关键词] 糖尿病肾病;miR-92b;PI3K;Akt;LY294002

[中图分类号] R587.2;R364.3          [文献标识码] A          [文章编号] 1673-9701（2021）30-0044-05

[Abstract] Objective To explore the relationship between miR-92b and PI3K/Akt signaling pathway in diabetic nephropathy. Methods Twelve 8-week-old male C57BL/6 mice were randomly divided into a normal control group and a diabetic nephropathy group. The diabetic nephropathy mouse model was established using sodium citrate. 12 bottles of human renal tubular epithelial HK-2 cells were selected and randomly divided into high glucose group， low glucose group and L-glucose group. The diabetic nephropathy cell model was established with high glucose stimulation. The expression levels of miR-92b in mouse kidney tissues and cells were detected by RT-PCR. The expression levels of Akt and P-Akt in mouse kidney tissues and cells were detected by Western blot. Results Compared with that of the control group，the expression level of miR-92b in the kidney tissue and cells of the diabetic nephropathy model group was significantly lower （P<0.05）， and the expression level of P-Akt/Akt was significantly higher（P<0.05）. The PI3K/Akt signaling pathway inhibitor LY294002 was added to the high glucose-induced diabetic nephropathy cell model. While PI3K/Akt signaling pathway was inhibited， the expression level of miR-92b was significantly increased（P<0.05）. Conclusion In diabetic nephropathy， miR-92b is negatively correlated with the expression of PI3K/Akt signaling pathway.

[Key words] Diabetic nephropathy; miR-92b; PI3K; Akt; LY294002

糖尿病腎病（Diabetic nephropathy，DN）是由糖尿病长期迁延不愈而致的肾脏微血管并发症，已是当前引起全球终末期肾脏疾病的主要病因之一[1]。由于导致DN的病因复杂多样，医学治疗效果有限，目前临床仍不能彻底治愈DN，只能维持治疗，延缓进展至终末期肾病。有研究表明[2]，microRNA-92b（miR-92b）可通过激活DOC-2/DAB2相互作用蛋白（DAB2 interactive protein，DAB2IP）下游信号通路PI3K/AKT促进胃癌细胞的生长，而此信号通路又在DN足细胞损伤、系膜细胞凋亡和肾小管细胞间质化等关键病变过程中起着不可替代的作用[3-5]。提示miR-92b与PI3K/AKT信号通路可能在DN病理变化中具有一定的相关性，目前国内外尚未见与此相关的文献报道。因此，为深入研究DN的发病机……