生殖医学杂志

目的 探讨黄芪甲苷Ⅳ(AS-Ⅳ)调节过氧化物酶体增殖物激活受体γ/核转录因子κB(PPARγ/NF-κB)通路对妊娠期糖尿病(GDM)大鼠胰岛素抵抗的影响。方法 SD孕鼠腹腔注射链脲佐菌素，构建GDM模型。将GDM大鼠随机分为模型组(GDM组)、黄芪甲苷Ⅳ低剂量组(AS-Ⅳ-L组)、黄芪甲苷Ⅳ中剂量组(AS-Ⅳ-M组)、黄芪甲苷Ⅳ高剂量组(AS-Ⅳ-H组)、黄芪甲苷Ⅳ高剂量+PPARγ抑制剂GW9622组(AS-Ⅳ-H+GW9622组),每组12只；另设正常孕鼠为对照组(Control组，n=12)。于末次干预后，测定大鼠空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)水平；全自动生化分析仪检测大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平；ELISA法检测大鼠血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α水平；HE染色观察大鼠胰岛组织病理学；Western blot检测PPARγ/NF-κB通路蛋白表达。结果 与Control组比较，GDM组大鼠FBG、FINS、HOMA-IR、TC、TG、LDL-C、IL-1β、IL-6、TNF-α和p-NF-κB p65水平显著升高(P<0.05),HDL-C和p-PPARγ水平显著降低(P<0.05),胰岛组织细胞数量减少、出现炎性细胞浸润；与GDM组比较，AS-Ⅳ-L组、AS-Ⅳ-M组、AS-Ⅳ-H组大鼠FBG、FINS、HOMA-IR、TC、TG、LDL-C、IL-1β、IL-6、TNF-α和p-NF-κB p65水平显著降低(P<0.05),HDL-C和p-PPARγ水平显著升高(P<0.05),胰岛组织细胞数量增加，炎性细胞浸润得到改善；GW9622可部分逆转AS-Ⅳ对GDM大鼠胰岛素抵抗的改善作用。结论 AS-Ⅳ可通过激活p-PPARγ来抑制p-NF-κB p65表达，进而降低GDM大鼠胰岛素抵抗。

Objectives:To investigate the effect of astragaloside Ⅳ(AS-Ⅳ) on insulin resistance in rats with gestational diabetes mellitus(GDM) by regulating the peroxisome proliferator activated receptor γ/nuclear factor kappa B(PPARγ/NF-κB) pathway.Methods:Streptozotocin was injected intraperitoneally into the pregnant rats to construct a GDM model. GDM rats were randomly assigned into the model group(GDM group),low-dose astragaloside Ⅳ group(AS-Ⅳ-L group),medium-dose astragaloside Ⅳ group(AS-Ⅳ-M group),high-dose astragaloside Ⅳ group(AS-Ⅳ-H group),high-dose astragaloside Ⅳ group + PPARγ inhibitor GW9622 group(AS-Ⅳ-H+GW9622 group),with 12 rats in each group. In addition, 12 normal pregnant rats were set as the Control group. After the last intervention, the levels of fasting blood glucose(FBG),fasting insulin(FINS),and insulin resistance index(HOMA-IR) in rats were measured. Fully automated biochemical analyzer was used to detect the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),and high density lipoprotein cholesterol(HDL-C) in serum. The enzyme-linked immunosorbent assay(ELISA) method was performed to detect the levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α in serum. HE staining was used to observe the pathology of pancreatic islet tissue. Moreover, Western blotting was used to detect the expression of PPARγ/NF-κB pathway proteins.Results:Compared with the control group, the levels of FBG,FINS,HOMA-IR,TC,TG,LDL-C,IL-1β,IL-6,TNF-α,and p-NF-κB p65 in GDM group were significantly higher(P<0.05),while HDL-C and p-PPARγ levels were significantly lower(P<0.05),and the number of pancreatic islet tissue cells decreased and inflammatory cell infiltration occurred. Compared with the GDM group, the FBG,FINS,HOMA-IR,TC,TG,LDL-C,IL-1β,IL-6,TNF-α,and p-NF-κB p65 levels in AS-Ⅳ-L group, AS-Ⅳ-M group, and AS-Ⅳ-H group were significantly lower(P<0.05),while HDL-C and p-PPARγ levels were significantly higher(P<0.05),and the number of pancreatic islet tissue cells increased, and inflammatory cell infiltration was improved. GW9622 could partially reverse the improvement effect of AS-Ⅳ on insulin resistance in GDM rats.Conclusions:AS-Ⅳ can inhibit the expression of p-NF-κB p65 by activating p-PPARγ,thereby reducing insulin resistance in GDM rats.