基于Nrf2/HO-1通路探讨黄芪甲苷对顺铂诱导的急性肾损伤的保护作用
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Astragaloside IV Has Protective Effect on Acute Kidney Injury Induced by Cisplatin Based on Nrf2/HO-1 Signaling Pathway
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    摘要:

    目的:探讨黄芪甲苷对核转录因子NF-E2相关因子2(Nrf2) /血红素氧合酶-1(HO-1) 通路的调控作用及对顺铂诱导的急性肾损伤(AKI) 的保护作用。方法:将大鼠按随机数字表法分为对照组、模型组、黄芪甲苷低、中、高剂量组5组,每组10 只。除对照组外,其余各组用顺铂按7 mg/kg 的剂量单次腹腔注射建立AKI 模型。黄芪甲苷低、中、高剂量组分别按5、10、20 mg/kg的剂量给予黄芪甲苷注射液,模型组和对照组给予生理盐水。用HE染色观察肾脏组织病理学改变;测定血清中肌酐(SCr) 和尿素氮(BUN) 含量;测定肾组织中谷胱甘肽过氧化物酶(GSH-Px) 和超氧化物歧化酶(SOD) 活性以及丙二醛(MDA) 含量;分别用蛋白质印迹法(Western blot)、逆转录聚合酶链式反应(RT-PCR) 检测Nrf2和HO-1蛋白及mRNA表达水平。结果:与对照组比较,模型组大鼠肾脏组织病理病变明显,可见肾小管坏死和退行性改变;与模型组比较,黄芪甲苷低、中、高组大鼠肾脏组织病理病变程度减轻,其中黄芪甲苷高剂量组最为明显。与对照组比较,模型组血清中SCr和BUN含量显著升高(P<0.05),肾组织中GSH-Px、SOD 活性显著降低(P<0.05),MDA 含量显著升高(P<0.05),Nrf2 和HO-1 相对蛋白表达和mRNA 水平显著降低(P<0.05);与模型组比较,黄芪甲苷低、中、高剂量组血清中SCr和BUN含量显著降低(P<0.05),肾组织中GSH-Px、SOD活性显著升高(P<0.05),MDA 含量显著降低(P<0.05),Nrf2和HO-1相对蛋白表达和mRNA 水平显著升高(P<0.05);与黄芪甲苷低剂量组比较,黄芪甲苷高剂量组血清中SCr和BUN含量显著降低(P<0.05),Nrf2和HO-1相对蛋白表达水平显著升高(P<0.05)。结论:黄芪甲苷可通过调控Nrf2/HO-1通路对顺铂诱导的AKI大鼠肾脏组织起显著的保护作用。

    Abstract:

    Abstract: Objective: To discuss the regulation of astragaloside IV on nuclear factor erythroid 2- related factor(Nrf2) /heme oxygenase - 1(HO- 1) signaling pathway and its protective effect on acute kidney injury(AKI) induced by cisplatin. Methods: Rats were divided into the control group, the model group, and the astragaloside IV groups of low- dose,medium- dose and high- dose according to the random number table method, 10 rats in each group. Except the control group, AKI models were established by single intraperitoneal injection with 7 mg/kg of cisplatin in the other groups. The astragaloside IV groups of low- dose, medium- dose and high- dose were respectively given 5, 10 and 20 mg/kg of astragaloside IV injection,and the model group and the control group were given saline. The pathological changes of the kidney tissue were observed by HE staining; the contents of serum creatinine(SCr) and blood urea nitrogen(BUN) were measured;the activity of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) and the content of malondialdehyde (MDA) in the kidney tissue were detected;the expression levels of protein and mRNA of Nrf2 and HO-1 were detected by Western blot and reverse transcriptase polymerase chain reaction(RT- PCR) respectively. Results: Compared with those in the control group, the pathological changes of the kidney tissue in the model group were more significant, with tubular necrosis and degenerative changes. Compared with that in the model group,the degree of pathological changes in the kidney tissue was decreased in the astragaloside IV groups of low-dose,medium-dose and high-dose,and the high-dose group had the most obvious decrease. Compared with those in the control group,in the model group,the contents of SCr and BUN in serum were significantly increased(P<0.05); the activities of GSH- Px and SOD in the kidney tissue were significantly decreased(P<0.05);the content of MDA was significantly increased(P<0.05);the relative expression levels of protein and mRNA of Nrf2 and HO-1 were significantly decreased(P<0.05). Compared with those in the model group,in the astragaloside IV groups of low-dose,medium-dose and high-dose,the contents of SCr and BUN in serum were significantly decreased (P<0.05);the activities of GSH-Px and SOD in the kidney tissue were significantly increased(P<0.05);the content of MDA was significantly decreased(P<0.05);the relative expression levels of protein and mRNA of Nrf2 and HO-1 were significantly increased(P<0.05). The contents of SCr and BUN in serum in the astragaloside IV group of high- dose were significantly decreased when compared with those in the astragaloside IV group of low-dose(P<0.05),and the relative expression levels of protein and mRNA of Nrf2 and HO- 1 were significantly increased(P<0.05). Conclusion:Astragaloside IV has significant protective effect on the kidney tissue in rats with AKI induced by cisplatin through regulating Nrf2/HO-1 signaling pathway.

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戢晴,韩颖敏.基于Nrf2/HO-1通路探讨黄芪甲苷对顺铂诱导的急性肾损伤的保护作用[J].新中医,2020,52(11):10-14

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  • 在线发布日期: 2020-06-04
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