健脾消渴方通过miR-126/IL-17A通路对2型糖尿病大鼠胰岛素抵抗及肾损伤的影响*

作者：吴阳阳，吴晓明，陈海兰，邓 舜

单位：海安市中医院，江苏 海安 226600

引用：引用：吴阳阳，吴晓明，陈海兰，邓舜.健脾消渴方通过miR-126/IL-17A通路对2型糖尿病大鼠胰岛素抵抗及肾损伤的影响[J].中医药导报,2026,32(3):12-17.

DOI：10.13862/j.cn43-1446/r.2026.03.003

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摘要：目的：探讨基于微小RNA-126（miR-126）/白细胞介素-17A（IL-17A）通路探讨健脾消渴方（JPXK）对2型糖尿病（T2DM）大鼠胰岛素抵抗（IR）及肾损伤的影响。方法：选择10只大鼠作为Control组，其余大鼠构建T2DM大鼠模型。将建模成功的大鼠随机分为T2DM组、L-JPXK组（灌胃10 g/kg的JPXK）、H-JPXK组（灌胃20 g/kg的JPXK）、miR-126 antagomir（拮抗剂）组（灌胃20 g/kg的JPXK+尾静脉注射20 nmol/mL miR-126 antagomir），每组各10只，T2DM组和Control组灌胃和注射等量生理盐水，每天灌胃3次，注射1次，连续28 d。检测常规生化指标[血肌酐（Scr）、尿素氮（BUN）、甘油三酯（TG）、总胆固醇（TC）]和胰岛素敏感性[空腹血糖（FBG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）]；qRT-PCR检测肾组织中miR-126 mRNA、IL-17A mRNA表达；HE染色观察肾损伤；TUNEL染色观察肾小管上皮细胞凋亡；酶联免疫吸附试验（ELISA）试剂盒检测肾组织中白细胞介素-1β（IL-1β），肿瘤坏死因子-α（TNF-α）表达；采用蛋白质印迹（Western blotting）法检测大鼠肾组织中剪切型胱天蛋白酶-3（cleaved Caspase-3）、IL-17A蛋白表达。结果：Control组大鼠肾脏结构清晰；T2DM组大鼠肾组织增生明显，细胞外基质增多，存在明显的炎症细胞浸润；L-JPXK组、H-JPXK组大鼠上述病变均有不同程度的改善；miR-126 antagomir组大鼠病变程度进一步加重。T2DM组大鼠Scr、BUN、TG、TC、FBG、FINS、HOMA-IR、肾小管上皮细胞凋亡率高于Control组（P<0.05），肾组织中IL-17A mRNA、IL-1β、TNF-α、cleaved Caspase-3、IL-17A表达高于Control组（P<0.05），miR-126 mRNA表达低于Control组（P<0.05）；L-JPXK组、H-JPXK组大鼠Scr、BUN、TG、TC、FBG、FINS、HOMA-IR、肾小管上皮细胞凋亡率低于T2DM组（P<0.05），肾组织中IL-17A mRNA、IL-1β、TNF-α、cleaved Caspase-3、IL-17A表达低于T2DM组（P<0.05），miR-126 mRNA表达高于T2DM组（P<0.05）；miR-126 antagomir组大鼠Scr、BUN、TG、TC、FBG、FINS、HOMA-IR、肾小管上皮细胞凋亡率高于H-JPXK组（P<0.05），肾组织中IL-17A mRNA、IL-1β、TNF-α、cleaved Caspase-3、IL-17A表达高于H-JPXK组（P<0.05），miR-126 mRNA表达低于H-JPXK组（P<0.05）。结论：JPXK能够改善T2DM大鼠的IR，减轻肾脏损伤，其作用机制可能是调控miR-126/IL-17A通路。

关键词：2型糖尿病；健脾消渴方；胰岛素抵抗；肾损伤；微小RNA-126/白细胞介素-17A通路；大鼠

Abstract：

Objective: To investigate the effect of Jianpi Xiaoke Formula (JPXK) on insulin resistance (IR) and renal injury in rats with type 2 diabetes mellitus (T2DM) and to explore the role of the microRNA-126 (miR-126)/interleukin-17A (IL-17A) pathway in this process. Methods: Ten normal rats served as the Control group, and the remaining rats were used to establish the T2DM rat model. Successfully modeled rats were randomly divided into the T2DM group, L-JPXK group (10 g/kg JPXK by gavage), H-JPXK group (20 g/kg JPXK by gavage), and miR-126 antagomir group (20 g/kg JPXK by gavage+20 nmol/mL miR-126 antagomir by tail vein injection), with 10 rats in each group.  Rats in the T2DM group and the Control group were given equal volumes of normal saline by gavage (three times daily) and by injection (once daily) for 28 consecutive days. Routine biochemical indicators [serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC)] and insulin sensitivity indicators [fasting blood glucose (FBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR)] were measured. qRT-PCR was used to detect the expression of miR-126 mRNA and IL-17A mRNA in renal tissue. HE staining was used to observe renal injury. TUNEL staining was used to observe apoptosis of renal tubular epithelial cells. Enzyme-linked immunoadsordent assay (ELISA) kits were used to detect the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in renal tissue. Western blotting was used to detect the expression of cleaved Caspase-3 and IL-17A proteins in rat renal tissue. Results: The renal structure was clear in the Control group. The T2DM group showed marked renal tissue proliferation, increased extracellular matrix, and obvious inflammatory cell infiltration. These lesions were ameliorated to varying degrees in the L-JPXK and H-JPXK groups, while they were further aggravated in the miR-126 antagomir group. Compared with the Control group, the T2DM group exhibited significantly higher levels of Scr, BUN, TG, TC, FBG, FINS, HOMA-IR, renal tubular epithelial cell apoptosis rate, as well as higher expression of IL-17A mRNA, IL-1β, TNF-α, cleaved Caspase-3, and IL-17A in renal tissue (P<0.05), while miR-126 mRNA expression was significantly lower (P<0.05). Compared with the T2DM group, the L-JPXK and H-JPXK groups showed significantly lower levels of Scr, BUN, TG, TC, FBG, FINS, HOMA-IR, renal tubular epithelial cell apoptosis rate, and lower expression of IL-17A mRNA, IL-1β, TNF-α, cleaved Caspase-3, and IL-17A in renal tissue (P<0.05), while miR-126 mRNA expression was significantly higher (P<0.05). Compared with the H-JPXK group, the miR-126 antagomir group showed significantly higher levels of Scr, BUN, TG, TC, FBG, FINS, HOMA-IR, renal tubular epithelial cell apoptosis rate, and higher expression of IL-17A mRNA, IL-1β, TNF-α, cleaved Caspase-3, and IL-17A in renal tissue (P<0.05), while miR-126 mRNA expression was significantly lower (P<0.05). Conclusion: Jianpi Xiaoke Formula can ameliorate IR and alleviate renal injury in T2DM rats, and its mechanism may be related to the regulation of the miR-126/IL-17A pathway.

Key words：type 2 diabetes mellitus; Jianpi Xiaoke Formula; insulin resistance; renal injury; microRNA-126/interleukin-17A pathway; rats

发布时间：2026-03-28

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