血红素加氧酶-l在大鼠肝硬化性肾损伤中的保护作用

Protective effects of heme oxygenase-l on renal damage due to hepatic cirrhosis

  • 摘要: 目的 探讨改变肝硬化大鼠肾中血红素加氧酶-1(heme oxygenase-1,HO-1)表达水平对肾的保护作用和可能的作用机制。 方法 将32只雄性SD大鼠随机分为4组:假手术组、肝硬化组、氯高铁血红素组和锌原卟啉组。胆总管结扎建立大鼠肝硬化模型,氯高铁血红素组胆总管结扎5周后隔日腹腔注射氯高铁血红素(30 μmol/kg),锌原卟啉组胆总管结扎5周后隔日腹腔注射锌原卟啉(10 μmol/kg)。4周后检测肾的各项生化指标,观察各组肾形态学改变,检测肾中HO-1的含量。 结果 肝硬化组血肌酐(serum creatinine,Scr)、胱抑素-C (cystatin C,Cys-C)、肌酐清除率(creatinine clearance rate,Ccr)水平分别为(44.52±3.31)μmol/L、(0.75±0.04) mg/L、(2.40±0.37) ml/min;氯高铁血红素组Scr、Cys-C、Ccr水平分别为(36.96±1.68)μmol/L、(0.50±0.03) mg/L、(3.40±0.62) ml/min;锌原卟啉组Scr、Cys-C、Ccr水平分别为(72.18±3.86)μmol/L、(0.91±0.05) mg/L、(1.03±0.30) ml/min。氯高铁血红素组Scr、Cys-C水平较肝硬化组明显降低(均P< 0.01),而Ccr明显升高(P< 0.01)。锌原卟啉组Scr、Cys-C水平较肝硬化组明显升高(均P< 0.01),而Ccr明显降低(P< 0.01)。且氯高铁血红素组肾组织病理明显改善。 结论 腹腔注射氯高铁血红素提高肝硬化大鼠肾中HO-1表达水平可以减轻肾损伤程度。

     

    Abstract: Objective To investigate the effect of heme oxygenase-l (HO-1) on renal damage due to hepatic cirrhosis and explore the possible mechanism. Methods Thirty-two male SD rats were randomly divided into four groups including sham group, hepatic cirrhosis group, Hemin group and Znpp group. Hepatic cirrhosis models of rats were established by common bile duct ligation, and then after 5 weeks, rats in the Hemin and Znpp groups received intraperitoneal injection of Hemin (30 μmol /kg) and Znpp (10 μmol /kg) on alternate days, respectively. The biochemical indexes of kidney, the renal morphology changes and the content of HO-1 protein in each group were observed and tested. Results The levels of Scr, Cys-C, Ccr were (44.52±3.31) μmol/L, (0.75±0.04) mg/L, (2.40±0.37) ml/min in hepatic cirrhosis group and (36.96±1.68) μmol/L, (0.50±0.03) mg/L, (3.40±0.62) ml/min in Hemin group and (72.18±3.86) μmol/L, (0.91±0.05) mg/L, (1.03±0.30) ml/min in Znpp group, respectively. The levels of Scr, Cys-C were signifcantly lower in Hemin group than in hepatic cirrhosis group and higher in Znpp group than in hepatic cirrhosis group (P< 0.01), and the level of Ccr was signifcantly higher in Hemin group than in hepatic cirrhosis group and lower in Znpp group than in hepatic cirrhosis group (P< 0.01). The renal pathological lesions were signifcantly improved in Hemin group. Conclusion Intraperitoneal injection of Hemin can improve the renal HO-1 protein expression in rats with liver cirrhosis, thus relieving the degree of kidney damage.

     

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