芍药苷对妊娠期糖尿病大鼠糖代谢、炎症、氧化应激的改善作用及机制 点击下载
论文标题： 芍药苷对妊娠期糖尿病大鼠糖代谢、炎症、氧化应激的改善作用及机制
英文标题：
中文摘要： 目的 基于核转录因子红系2相关因子2（Nrf2）/血红素加氧酶1（HO-1）/依赖还原型辅酶/醌氧化还原酶1（NQO1）信号通路探究芍药苷对妊娠期糖尿病（GDM）大鼠糖代谢、炎症、氧化应激的改善作用及潜在机制。方法将以高脂高糖饲料喂养的雌性大鼠和以普通饲料喂养的雄性大鼠合笼，收集妊娠期大鼠，单次腹腔注射链脲佐菌素复制GDM模型。将造模成功的大鼠随机分为模型组，盐酸二甲双胍组（灌胃200mg/kg盐酸二甲双胍），芍药苷低、高剂量组（分别灌胃45、90mg/kg芍药苷），芍药苷+ML385组（灌胃90mg/kg芍药苷并腹腔注射30mg/kgNrf2抑制剂ML385），每组12只；另取以普通饲料喂养的妊娠期大鼠12只，作为对照组。各组大鼠给予相应药物/生理盐水，每天1次，连续干预2周。检测其糖代谢指标[空腹血糖（FBG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）]、血清炎症因子[白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）]和肾组织氧化应激指标[超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）]水平，观察肾组织病理变化，并检测肾组织中Nrf2、HO-1、NQO1蛋白的表达情况。结果与对照组相比，模型组大鼠肾组织病变明显，可见肾小球萎缩、肾小管上皮细胞水肿变性和大量炎症细胞浸润；FBG、FINS水平，HOMA-IR，血清IL-6、TNF-α水平，以及肾组织中MDA水平均显著升高（P＜0.05）；肾组织中SOD、GSH-Px水平和Nrf2、HO-1、NQO1蛋白的表达水平均显著降低（P＜0.05）。与模型组相比，芍药苷低、高剂量组大鼠肾组织病变有所减轻，上述各定量指标均显著改善，且芍药苷高剂量组的改善效果更优（P＜0.05）；ML385可显著逆转芍药苷对上述指标的改善作用（P＜0.05）。结论芍药苷可改善GDM大鼠的糖代谢异常、炎症和肾组织氧化应激损伤，上述作用可能与激活Nrf2/HO-1/NOQ1信号通路有关。
英文摘要： OBJECTIVE To explore the effect of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on nuclear factor-erythroid 2-related factor 2 （Nrf2）/ heme oxygenase-1 （HO-1）/nicotinamide adenine dinucleotide phosphate：quinone oxidoreductase 1 （NQO1） signaling pathway. METHODS The female rats fed with high fat and high sugar diet and the male rats fed with an ordinary diet were caged， the successfully conceived rats were collected， and streptozotocin was injected intraperitoneally once to induce the GDM model. The successfully modeled rats were randomly divided into the model group， metformin hydrochloride group （200 mg/kg metformin by gavage）， paeoniflorin low-， high-dose groups （45， 90 mg/kg paeoniflorin by gavage， respectively）， paeoniflorin+ML385 group （90 mg/kg paeoniflorin by gavage and intraperitoneal injection of 30 mg/kg Nrf2 inhibitor ML385）， with 12 rats in each group； in addition， another 12 conceived rats fed with an ordinary diet were selected as the control group. The rats in each drug group were given the corresponding drug/normal saline， once a day， for 2 consecutive weeks. Glucose metabolism indexes [fasting blood glucose （FBG）， fasting insulin （FINS）， insulin resistance index （HOMA-IR）]， serum inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor- α （TNF- α）] and renal tissue oxidative stress indexes [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）] were detected； the pathological changes of renal tissue were observed， and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were detected. RESULTS Compared with the control group， the renal tissue lesions of the model group were obvious， including glomerular atrophy， edema degeneration of renal tubular epithelial cells and a large number of inflammatory cell infiltration； the levels of FBG and FINS， HOMA-IR， the levels of IL-6 and TNF-α in serum， and the level of MDA in renal tissue were significantly increased （P＜0.05）， while the levels of SOD and GSH-Px and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were significantly decreased （P＜0.05）. Compared with the model group， the renal tissue lesions of rats in paeoniflorin low-dose and high-dose groups were reduced， the above quantitative indexes were significantly improved， and the improvement effect was better in high-dose group （P＜0.05）， while ML385 could significantly reverse the improvement effect of paeoniflorin on the above indexes （P＜0.05）. CONCLUSIONS Paeoniflorin can improve the abnormal glucose metabolism， inflammation and oxidative stress damage of renal tissue in GDM rats， which may be related to the activation of Nrf2/HO-1/NOQ1 signaling pathway.
期刊： 2024年第35卷第12期
作者： 刘桂英；牛丽；常雪允；周秀云
英文作者： LIU Guiying，NIU Li，CHANG Xueyun，ZHOU Xiuyun
关键字： 芍药苷；妊娠期糖尿病；炎症；氧化应激；Nrf2/HO-1/NQO-1信号通路
KEYWORDS： paeoniflorin； gestational diabetes mellitus； inflammation； oxidative stress； Nrf2/HO-1/NQO-1 signaling pathway
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