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目的探讨姜黄素对汞致大鼠肾损伤的影响,为汞中毒的发病机制和防治提供实验依据。方法将30只清洁级Wistar大鼠按体重随机分为5组,分别为对照(生理盐水)组和2.2、4.4、8.8μmol/kg氯化汞染毒组及姜黄素干预(8.8mol/kg氯化汞+100 mg/kg姜黄素)组,每组6只,雌雄各半。采用腹腔注射方式染毒氯化汞,染毒容量为5 ml/kg;采用皮下注射方式染毒姜黄素,染毒容量为1 ml/kg,每天1次,连续染毒3 d。测定肾皮质汞含量、肾皮质细胞ROS水平和细胞凋亡率及肾皮质Nrf2、HO-1、γ-GCS和Gpx-1 mRNA和蛋白的表达水平。结果与对照组比较,各剂量氯化汞染毒组和姜黄素干预组大鼠肾皮质汞含量和细胞凋亡率均升高,4.4、8.8μmol/kg氯化汞染毒组和姜黄素干预组大鼠肾皮质细胞ROS水平均升高,差异有统计学意义(P<0.05,P<0.01)。与对照组比较,各剂量氯化汞染毒组和姜黄素干预组大鼠肾皮质Nrf2、HO-1、γ-GCS mRNA的表达水平均升高,而Gpx-1 mRNA的表达水平均降低,除2.2μmol/kg氯化汞染毒组HO-1、GPx-1mRNA的表达水平及姜黄素干预组GPx-1 mRNA的表达水平外,差异均有统计学意义(P<0.05,P<0.01)。与对照组比较,各剂量氯化汞染毒组和姜黄素干预组大鼠肾皮质Nrf2、HO-1、γ-GCS蛋白的表达水平均升高,而Gpx-1蛋白的表达水平均降低,除2.2μmol/kg氯化汞染毒组γ-GCS蛋白的表达水平外,差异均有统计学意义(P<0.05,P<0.01)。且随着氯化汞染毒剂量的升高,大鼠肾皮质汞含量、ROS水平和细胞凋亡率及肾皮质Nrf2、HO-1、γ-GCS蛋白和mRNA的表达水平均呈上升趋势,而GPx-1蛋白的表达水平呈下降趋势。与8.8μmol/kg氯化汞染毒组比较,姜黄素干预组大鼠肾皮质ROS水平和细胞凋亡率均下降,差异有统计学意义(P<0.01),而肾皮质汞含量无明显改变;肾皮质Nrf2、HO-1、γ-GCS和GPx-1mRNA的表达水平均升高,差异有统计学意义(P<0.01);肾皮质γ-GCS、HO-1蛋白的表达水平均升高,而Nrf2、GPx-1蛋白的表达水平降低,差异有统计学意义(P<0.01)。结论姜黄素可通过激活Nrf2信号通路对汞致大鼠肾损伤产生一定的拮抗作用。
Objective To investigate the effect of curcumin on renal injury induced by mercury and provide experimental evidence for the pathogenesis and prevention of mercury poisoning. Methods Thirty Wistar rats of clean grade were randomly divided into five groups according to body weight: control (saline) group and 2.2, 4.4, 8.8μmol / kg mercuric chloride treatment group and curcumin intervention (8.8mol / kg chlorine Hg + 100 mg / kg curcumin) group, 6 in each group, male and female. The intraperitoneal injection of mercury chloride, exposure capacity of 5 ml / kg; subcutaneous injection of curcumin poisoning, exposure capacity of 1 ml / kg, 1 times a day, continuous exposure to 3 d. The renal cortical mercury level, ROS level and apoptotic rate of renal cortical cells and the expression of Nrf2, HO-1, γ-GCS and Gpx-1 mRNA and protein in renal cortex were measured. Results Compared with the control group, the contents of mercury and apoptosis in the renal cortex of rats in each group treated with mercuric chloride and curcumin were significantly higher than those in the control group (4.4 and 8.8 μmol / kg, respectively) and curcumin The level of ROS in renal cortical cells of rats increased significantly, the difference was statistically significant (P <0.05, P <0.01). Compared with the control group, the expression levels of Nrf2, HO-1 and γ-GCS mRNA in the renal cortex and the expression of Gpx-1 mRNA in the groups treated with mercuric chloride and curcumin were all decreased, Except the expression of HO-1 and GPx-1mRNA and the expression of GPx-1mRNA in curcumin intervention group with 2.2μmol / kg mercuric chloride treatment, the differences were statistically significant (P <0.05, P <0.01) . Compared with the control group, the expressions of Nrf2, HO-1 and γ-GCS protein in the renal cortex and the expression of Gpx-1 protein were decreased in the groups treated with mercuric chloride and curcumin, Except γ-GCS protein expression in 2.2μmol / kg mercuric chloride treatment group, the differences were statistically significant (P <0.05, P <0.01). With the increase of the dose of mercuric chloride, the content of mercury, the level of ROS and the rate of apoptosis in renal cortex and the expressions of Nrf2, HO-1, γ-GCS protein and mRNA in renal cortex all showed an upward trend, While the expression of GPx-1 protein showed a downward trend. Compared with the 8.8μmol / kg mercuric chloride treatment group, the levels of ROS and apoptosis in renal cortex were decreased in the curcumin-treated group (P <0.01), while there was no significant change in the renal cortex ; The expression of Nrf2, HO-1, γ-GCS and GPx-1mRNA in renal cortex increased, the difference was statistically significant (P <0.01); the expression of γ-GCS and HO- , While the expression of Nrf2 and GPx-1 protein decreased, with statistical significance (P <0.01). Conclusion Curcumin can antagonize the renal injury caused by mercury in rats by activating the Nrf2 signaling pathway.