【目的】 探讨黄芩苷对妊娠期糖尿病（GDM）大鼠的治疗作用及机制。【方法】 采用高脂高糖饮食联合链脲佐菌素（STZ）注 射法诱导构建 GDM 大鼠模型。将造模成功的 40只大鼠随机分为模型组，二甲双胍组，黄芩苷低、高剂量组和黄芩苷高剂 量+ ML385[核因子红细胞系2相关因子2（Nrf2）抑制剂]组，每组8只，另设正常组（健康大鼠80只）。分组干预后，检测空腹 血糖（FBG）、空腹胰岛素（FINS）以及稳态模型的胰岛素抵抗指数（HOMA-IR）水平，血清谷丙转氨酶（ALT）、谷草转氨酶 （AST）、碱性磷酸酶（ALP）水平，肝脏组织超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化 氢酶（CAT）水平，采用酶联免疫吸附分析（ELISA）检测大鼠血清炎症因子指标肿瘤坏死因子 α（TNF-α）、白细胞介素 1β （IL-1β）、白细胞介素 6（IL-6）水平，采用苏木精-伊红（HE）染色法检测肝脏组织病理变化，采用蛋白免疫印迹（Western Blot）法检测大鼠肝脏组织中 Nrf2、血红素氧合酶 1（HO-1）蛋白表达水平。【结果】 与正常组比较，模型组大鼠 FBG、FINS、 HOMA-IR，ALT、AST、ALP，TNF-α、IL-1β、IL-6，MDA 等水平显著升高（P＜0.05），而 SOD、CAT、GSH-Px 水平及 Nrf2、HO-1表达水平显著降低（P＜0.05），肝组织 HE 染色病理可见细胞排列紊乱，细胞大面积变性坏死。与模型组比较， 二甲双胍组、黄芩苷高剂量组以及黄芩苷高剂量+ML385 组 FBG、FINS、HOMA-IR，ALT、AST、ALP，TNF-α、IL-1β、 IL-6，MDA等水平显著降低（P＜0.05），而SOD、CAT、GSH-Px水平及Nrf2、HO-1表达水平显著升高（P＜0.05），肝窦组织 结构好转，坏死细胞减少；与黄芩苷低剂量组比较，黄芩苷高剂量组 FBG、FINS、HOMA-IR，ALT、AST、ALP，TNF-α、 IL-1β、IL-6，MDA 等水平显著降低（P＜0.05），而 SOD、CAT、GSH-Px 水平及 Nrf2、HO-1 表达水平显著升高（P＜0.05）， 肝窦组织结构好转，坏死细胞减少；与黄芩苷高剂量组比较，黄芩苷高剂量+ML385组上述指标均得到逆转（P＜0.05）。【结论】 黄芩苷能够通过激活Nrf2、HO-1表达改善GDM大鼠氧化应激损伤。

Objective To explore the therapeutic effect and mechanism of baicalin on gestational diabetes mellitus （GDM） rats. Methods A GDM rat model was induced by a high-fat high-glucose diet combined with Streptozotocin （STZ） Injection. Forty modeled successfully rats were randomly divided into model group，Metformin group，lowand high-dose baicalin group and high-dose baicalin + ML385 [nuclear factor erythroid 2-related factor 2（Nrf2） inhibitor] group，with 8 rats in each group，in addition，the normal group（8 healthy rats） was set up. After group intervention，fasting blood glucose（FBG），fasting insulin（FINS），and homeostasis model assessment of insulin resistance（HOMA-IR） levels were measured. Serum levels of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， and alkaline phosphatase（ALP） were detected. The levels of superoxide dismutase （SOD）， malondialdehyde（MDA）， glutathione peroxidase（GSH-Px），and catalase（CAT） in liver tissue were measured. Enzyme-linked immunosorbent assay（ELISA） was used to detect serum inflammatory factors，including tumor necrosis factor α（TNF-α），interleukin 1β（IL-1β），and interleukin 6（IL-6）. Hematoxylin-eosin（HE） staining was used to observe liver histopathological changes. Western Blot was used to detect the protein expression levels of Nrf2 and heme oxygenase-1（HO-1） in rat liver tissue. Results Compared with the normal group，the model group showed significantly increased levels of FBG，FINS，HOMA-IR，ALT，AST，ALP，TNF- α， IL-1β，IL-6 and MDA（P＜0.05），while the levels of SOD，CAT，GSH-Px，and the expression levels of Nrf2 and HO-1 were significantly decreased（P＜0.05）. HE staining of liver tissue revealed disordered cell arrangement and extensive cell degeneration and necrosis. Compared with the model group，the Metformin group，high-dose baicalin group， and high-dose baicalin +ML385 group showed significantly decreased levels of FBG， FINS， HOMA-IR，ALT，AST，ALP，TNF-α，IL-1β，IL-6 and MDA（P＜0.05），while the levels of SOD，CAT， GSH-Px，and the expression levels of Nrf2 and HO-1 were significantly increased（P＜0.05）. The structure of liver sinusoids improved，and necrotic cells were reduced. Compared with the low-dose baicalin group，the highdose baicalin group showed significantly decreased levels of FBG， FINS， HOMA-IR， ALT， AST， ALP， TNF- α，IL-1β，IL-6 and MDA（P＜0.05），while the levels of SOD，CAT，GSH-Px，and the expression levels of Nrf2 and HO-1 were significantly increased（P＜0.05）. The structure of liver sinusoids improved，and necrotic cells were reduced. Compared with the high-dose baicalin group，the high-dose baicalin+ML385 group showed a reversal in the above indicators（P＜0.05）. Conclusion Baicalin can alleviate oxidative stress injury in GDM rats by activating Nrf2 and HO-1 expression.

R285.5

陕西省重点研发计划项目（编号：2022SF-0251）