【目的】 探讨人参皂苷Rb1对2型糖尿病（T2DM）大鼠的治疗作用及机制。【方法】 将大鼠随机分为正常组和造模组。除 正常组，造模组大鼠采用饲喂高脂高糖饮食+腹腔注射链脲佐菌素（STZ）诱导法建立T2DM模型。将造模成功的大鼠随机分为 模型组，人参皂苷Rb1低、高剂量组和通路激活剂组，每组12只。连续干预8周。干预结束后，观察血糖和肾功能相关指标 24 h尿蛋白、血清尿素氮（BUN）、血清肌酐（SCr）水平；采用苏木精-伊红（HE）染色法观察肾组织病理形态；实时定量聚合 酶链反应（RT-qPCR）法检测肾组织中炎症因子肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β和IL-6基因水平；酶联免疫吸 附分析（ELISA）检测肾组织氧化应激指标活性氧（ROS）、丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）水平； Western Blot法检测肾组织中干扰素基因刺激蛋白（STING）/TANK结合激酶1（TBK1）/干扰素调节因子3（IRF3）通路相关蛋白表 达水平。【结果】 与正常组比较，模型组大鼠肾小球明显肥大、基底膜增厚，肾间质有大量炎性细胞浸润，血糖，肾功能相 关指标，TNF-α、IL-1β、IL-6 mRNA 表达水平及 ROS、MDA 水平显著增加（P＜0.05），GSH 和 SOD 水平显著降低（P＜ 0.05）；与模型组比较，人参皂苷Rb1低、高剂量组大鼠肾小球和肾小管结构损伤有所改善，肾间质炎症减轻，血糖和肾脏 功能相关指标，TNF-α、IL-1β、IL-6 mRNA 表达水平以及 ROS、MDA水平显著降低（P＜0.05），GSH和 SOD水平显著增加 （P＜0.05），其中高剂量组整体治疗效果更好；通路激活剂组各指标水平与高剂量组比较，则呈现相反趋势。【结论】 人参皂 苷Rb1能够改善T2DM大鼠肾脏损伤，减轻炎症反应和氧化应激，其机制可能与抑制STING/TBK1/IRF3信号通路激活有关。

Objective To investigate the therapeutic effect of Ginsenoside Rb1 on type 2 diabetes mellitus （T2DM） rats and its underlying mechanism. Methods Rats were randomly divided into a normal group and a modeling group. Except for the normal group，T2DM models were established in the modeling group rats by feeding a high-fat，high-sugar diet combined with intraperitoneal injection of streptozotocin （STZ）. Successfully modeled rats were then randomly divided into a model group， a low-dose Ginsenoside Rb1 group， a high-dose Ginsenoside Rb1 group，and a pathway activator group，with 12 rats in each group. Continuous intervention lasted for 8 weeks. After the intervention， blood glucose and serum levels of kidney function-related indicators， including 24-hour urinary protein，blood urea nitrogen （BUN），and serum creatinine （SCr），were measured. The pathological morphology of renal tissue was observed by hematoxylin-eosin （HE） staining. The mRNA levels of inflammatory factors tumor necrosis factor-alpha （TNF-α），interleukin-1β（IL-1β），and IL-6 in renal tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. Renal oxidative stress indicators， including reactive oxygen species （ROS），malondialdehyde （MDA），glutathione （GSH），and superoxide dismutase （SOD）， were measured by enzyme-linked immunosorbent assay （ELISA）. The expression levels of proteins related to the stimulator of interferon genes （STING） / TANK-binding kinase 1（TBK1） / interferon regulatory factor 3（IRF3） pathway in the kidney were detected by Western Blot. Results Compared with the normal group， rats in the model group exhibited significant glomerular hypertrophy， thickened basement membrane， and extensive inflammatory cell infiltration in the renal interstitium. Blood glucose，kidney function-related indicators， mRNA expression levels of TNF- α，IL-1β，and IL-6，as well as levels of ROS and MDA were significantly increased （P＜0.05），while levels of GSH and SOD were significantly decreased （P＜0.05）. Compared with the model group，rats in the low-dose and high-dose Ginsenoside Rb1 groups showed ameliorated structural damage to glomeruli and renal tubules，reduced renal interstitial inflammation，and significantly decreased blood glucose， kidney function-related indicators，mRNA expression levels of TNF-α，IL-1β，IL-6，as well as levels of ROS and MDA （P＜0.05）. Levels of GSH and SOD were significantly increased （P＜0.05），with the high-dose group demonstrating better overall therapeutic efficacy. Compared with the high-dose group， the levels of various indicators in the pathway activator group showed opposite trends. Conclusion Ginsenoside Rb1 can ameliorate renal injury，alleviate inflammatory response and oxidative stress in T2DM rats. The mechanism may be related to the inhibition of the STING/TBK1/IRF3 signaling pathway activation.

R285.5

云南省卫生健康委临床医学中心2022-2024年建设项目（编号：202201AF170048）