橙皮苷对脓毒症所致急性肾损伤大鼠的作用及其机制

Effects and mechanism of hesperidin on sepsis-induced acute kidney injury in rats

目的探讨橙皮苷对脓毒症所致急性肾损伤(AKI)大鼠肾脏的保护作用及其机制。方法取28只SD雄性大鼠,采用盲肠结扎和穿刺法建立脓毒症大鼠模型,从建模成功的20只大鼠中抽取18只随机均分为模型组、低剂量(橙皮苷25 mg·kg^-1)组、高剂量(橙皮苷50 mg·kg^-1)组,另取6只大鼠设为对照组。术后24 h,模型组、低剂量组和高剂量组分别给予生理盐水和对应剂量的橙皮苷腹腔注射,每日1次,共2 d。检测各组肾功能、肾组织细胞凋亡情况,评估肾脏病理损伤评分。检测肾组织炎症因子表达水平和氧化应激指标,Western blotting法检测肾组织Bcl-2、Bax、核因子-κB(NF-κB)蛋白表达水平。结果与对照组比较,模型组肾脏病理损伤评分、血清尿素氮和肌酐水平,肾脏细胞凋亡指数、Bax和NF-κB蛋白表达水平,肾组织白细胞介素(IL)^-1β、IL-6和肿瘤坏死因子(TNF)-α表达水平,丙二醛(MDA)含量均增高,差异均有显著意义(P<0.05);与模型组相比,高剂量组和低剂量组前述指标均降低(P<0.05),且高剂量组指标均低于低剂量组(P<0.05)。与对照组比较,模型组肾组织Bcl-2蛋白表达水平、锰超氧化物歧化酶(MnSOD)和谷胱甘肽过氧化物酶(GSH-Px)活性降低,差异均有显著意义(P<0.05);与模型组相比,高剂量组和低剂量组前述指标均升高,且高剂量组高于低剂量组(P<0.05)。结论橙皮苷对脓毒症所致AKI大鼠肾脏有一定的保护作用,降低炎症因子水平、抑制氧化应激和凋亡可能是其作用机制。

AIM To investigate the protective effect of hesperetin on sepsis-induced acute kidney injury(AKI)in rats and its mechanism.METHODS Twenty-eight SD male rats were taken and the septic rat model was established by cecal ligation and puncture.Eighteen of 20 rats successfully modeled were randomly divided into model group,lowdose(hesperidin 25 mg·kg^-1)group and high-dose(hesperidin 50 mg·kg^-1)group,and another six rats were set as the control group.Twenty-four hours after operation,the model group,low-dose group and high-dose group were given intraperitoneal injection of normal saline and corresponding dose of hesperidin once a day for 2 days.The apoptosis of renal tissue and renal function in each group was detected,and the pathological injury score of kidney was evaluated.The expression levels of inflammatory factors and oxidative stress were detected,and the protein levels of Bcl-2,Bax and nuclear factor-κB(NF-κB)were detected by Western blotting method.RESULTS Compared with the control group,the renal pathological damage score,blood urea nitrogen and serum creatinine levels,renal cell apoptosis index,Bax and NF-κB protein expression level,and levels of IL^-1β,IL-6,TNF-αand malondialdehyde in kidney of the model group were higher(P<0.05).Compared with the model group,the above-mentioned indexes in the high-dose group and the lowdose group were reduced(P<0.05),and the indexes in the high-dose group were lower than those in the low-dose group(P<0.05).Compared with the control group,Bcl-2 protein expression level,manganese superoxide dismutase and glutathione peroxidase activities in the model group were decreased,and the differences were significant(P<0.05).Compared with the model group,the above-mentioned indexes of the high-dose group and the low-dose group were all increased,and the high-dose group was higher than the low-dose group(P<0.05).CONCLUSION Hesperidin has a protective effect on kidney of rats with septic-induced AKI,which may be caused by reducing inflammatory factors,inhibiting oxidative stress and apoptosis.