黄连对糖耐量异常大鼠肾损伤保护作用及Nrf2/HO-1通路的影响

Protective effect of Coptis chinensis on renal injury and Nrf2/HO-1 pathway in rats with impaired glucose tolerance

目的研究黄连对糖耐量异常大鼠肾损伤保护作用及Nrf2/HO-1通路的影响。方法采用腹腔注射D-半乳糖溶液制备糖耐量异常大鼠模型,灌胃6周,对照组和模型组用生理盐水灌胃(0.1 mL/kg体质量)、黄连低剂量组(黄连1.25 g/kg体质量)、黄连高剂量组(黄连5 g/kg体质量)和二甲双胍组(150 mg/kg体质量),测定空腹血糖(FBG)和餐后2 h血糖(2 h BG),对大鼠肾脏进行病理学检测,检测血清中胱抑素C(Cys-C)、β2-微球蛋白(β2-MG)、丙二醛(MDA)和总抗氧化能力(TAOC)水平,测定肾组织中核因子E-2相关因子(Nrf2)、血红素加氧酶1(HO-1)和磷酸酰胺腺嘌呤二核苷酸醌氧化还原酶-1(NQO-1)水平。结果对照组大鼠肾组织未见明显的组织学改变;模型组大鼠肾脏肾小管严重损伤和坏死、炎性细胞浸润;各黄连剂量组和二甲双胍组肾小管损伤、炎性细胞浸润较模型组减轻;各组大鼠FBG水平差异均无统计学意义(P>0.05)。与对照组相比,其余各组大鼠2 h BG、Cys-C、β2-MG和MDA水平增加,T-AOC、Nrf2、HO-1和NQO-1水平降低,差异有统计学意义(P<0.05)。与模型组相比,各黄连剂量组和二甲双胍组大鼠2 h BG、Cys-C、β2-MG和MDA水平降低,T-AOC、Nrf2、HO-1和NQO-1水平增加,差异有统计学意义(P<0.05)。结论黄连可保护糖耐量异常大鼠肾损伤并激活Nrf2/HO-1信号通路。

Objective To investigate the protective effect of Coptis chinensis on renal injury and Nrf2/HO-1 pathway in rats with impaired glucose tolerance.Methods D-galactose solution was injected intraperitoneally to establish the rat model of impaired glucose tolerance.The rats in control group and model group,low-and high-dose of Coptis group(1.25 and 5g/kg)and metformin group(150 mg/kg)were intragastrically administered for 6 weeks.Fasting blood glucose(FBG)and 2 h postprandial blood glucose(2h BG)were measured.The kidney of rats was examined by pathology.The levels of cystatin C(Cys-C),β2-microglobulin(β2-MG),malondialdehyde(MDA)and total antioxidant capacity(T-AOC)in serum were detected.The levels of nuclear factor E-2-related factor(Nrf2),heme oxygenase-1(HO-1)and phosphoramide adenine dinucleotide quinone oxidoreductase-1(NQO-1)in kidney were determined.Results No obvious histological changes were observed in the kidney tissues of rats in the control group.Severe renal tubular injury and necrosis,inflammatory cell infiltration were observed in the model group.Tubular injury and inflammatory cell infiltration were reduced in the Coptis dose group and metformin group compared with the model group.The FBG levels of rats in each group were not significantly different(P>0.05).Compared with the control group,the levels of 2hBG,Cys-C,β2-MG and MDA in the other groups were significantly increased,while the levels of T-AOC,Nrf2,HO-1 and NQO-1 decreased(P<0.05).Compared with the model group,the levels of BG,Cys-C,β2-MG and MDA were significantly decreased,while the levels of T-AOC,Nrf2,HO-1 and NQO-1 increased in the Coptis chinensis groups,but the effects were not as good as those of metformin group(P<0.05).Conclusion Coptis chinensis can protect renal injury and activate Nrf2/HO-1 signaling pathway in rats with impaired glucose tolerance.