原花青素通过SIRT1/AMPK信号通路对庆大霉素致大鼠急性肾损伤的改善机制
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篇名: 原花青素通过SIRT1/AMPK信号通路对庆大霉素致大鼠急性肾损伤的改善机制
TITLE: Improvement mechanism of proanthocyanidins on gentamicin-induced acute kidney injury of rats through SIRT1/AMPK signaling pathway
摘要: 目的 探究原花青素对庆大霉素致大鼠急性肾损伤(AKI)的改善机制。方法通过腹腔注射硫酸庆大霉素构建AKI大鼠模型,将造模成功的大鼠随机分为模型对照组、盐酸贝那普利5mg/kg组(阳性对照)、原花青素50mg/kg组、原花青素100mg/kg组、原花青素200mg/kg组,每组10只;另取10只正常大鼠作为正常对照组。各给药组大鼠灌胃相应药液,正常对照组和模型对照组大鼠灌胃等体积生理盐水。所有大鼠每天给药1次,连续28d。末次给药后,检测血清中血清肌酐(SCr)、尿素氮(BUN)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)及24h尿液中尿蛋白(UP)水平;计算肾脏指数;观察大鼠肾组织病理变化并进行病理评分;检测肾组织细胞凋亡率和胱天蛋白酶-3(Caspase-3)、B细胞淋巴瘤2基因相关X蛋白(Bax)表达水平,以及沉默信息调节因子1(SIRT1)、AMP活化蛋白激酶(AMPK)蛋白的磷酸化水平。结果与模型对照组比较,各给药组大鼠SCr、BUN、UP、MDA水平,肾脏指数,肾组织病理评分,肾组织细胞凋亡率及肾组织中Caspase-3、Bax蛋白表达水平均显著降低,SOD、GSH-Px水平和肾组织中SIRT1、AMPK蛋白的磷酸化水平均显著升高(P<0.05),且原花青素的作用存在剂量依赖性(P<0.05);原花青素200mg/kg组与盐酸贝那普利5mg/kg组比较,上述指标差异均无统计学意义(P>0.05)。结论原花青素对AKI大鼠的改善作用可能与其激活SIRT1/AMPK信号通路进而抑制氧化应激有关。
ABSTRACT: OBJECTIVE To explore the improvement mechanism of proanthocyanidins on acute kidney injury (AKI) induced by gentamicin in rats. METHODS Gentamicin sulfate was injected intraperitoneally to construct the AKI rat model; the model rats were randomly divided into model control group, benazepril hydrochloride 5 mg/kg group (positive control), proanthocyanidins 50 mg/kg group, proanthocyanidins 100 mg/kg group, and proanthocyanidins 200 mg/kg group, with 10 rats in each group; in addition, 10 normal rats were selected to be treated as the normal control group. The rats in each administration group were given corresponding liquid intragastrically, and the normal control group and model control group were given equal volumes of normal saline intragastrically, once a day, for 28 consecutive days. After the last administration, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and 24 h urinary protein (UP) were detected; the renal index was calculated; the pathological changes of renal tissue were observed and the pathological score was calculated; the apoptotic rate of cells in renal tissue and the expression levels of Caspase-3 and Bcl-2 associated X protein (Bax), as well as the phosphorylation levels of silent information regulator of transcription 1 (SIRT1) and AMP-activated protein kinase (AMPK) were detected. RESULTS Compared with the model control group, the levels of SCr, BUN, UP and MDA, the renal index, the pathological score of renal tissue, the apoptotic rate of cells in renal tissue, the protein expression levels of Caspase-3 and Bax in renal tissue of rats in each administration group were decreased significantly; SOD and GSH-Px levels, phosphorylation levels of SIRT1 and AMPK protein were increased significantly (P<0.05), and the effect of proanthocyanidins was in a dose-dependent manner (P<0.05). There were no significant differences in the above indexes between proanthocyanidins 200 mg/kg group and benazepril hydrochloride 5 mg/kg group (P>0.05). CONCLUSIONS The improvement effect of proanthocyanidins on AKI rats may be related to the activation of SIRT1/AMPK signaling pathway to inhibit oxidative stress.
期刊: 2024年第35卷第07期
作者: 符妹丽;江强;符圣亮;符书山;谢桃梅;黎珊珊
AUTHORS: FU Meili,JIANG Qiang,FU Shengliang,FU Shushan,XIE Taomei,LI Shanshan
关键字: 原花青素;SIRT1/AMPK信号通路;急性肾损伤;氧化应激
KEYWORDS: proanthocyanidins; SIRT1/AMPK signaling pathway; acute kidney injury; oxidative stress
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