硫胺素对实验性铅性肾病的治疗作用及其对纤维连接蛋白表达的影响

Effect of thiamine on prevention of experimental lead nephropathy and expression of fibronectin

目的观察硫胺素对铅性肾病的治疗作用,并从蛋白质和分子水平观察其对纤维连接蛋白(FN)表达的影响。方法SD大鼠72只适应性饲养1周,随机分为3组:正常对照组、染铅组、硫胺素组,每组又根据喂饮时间的不同分3个亚组。正常对照组予蒸馏水喂饮;染铅组给予0.5%的醋酸铅喂饮;硫胺素组在给予0.5%的醋酸铅喂饮的同时予硫胺素3mg/100g体重,注射用水稀释、灌胃每天一次。各组分别喂饮1,2,3个月。然后用原子吸收光谱石墨炉法测血铅含量;用热消化法测肾铅含量;用免疫组化的方法检测肾组织FN蛋白的表达,用RT-PCR的方法检测肾组织FN mRNA的表达。结果硫胺素组喂饮3个月后,大鼠血铅含量较染铅组显著下降。硫胺素组喂饮2个月后,大鼠肾铅含量较染铅组也明显降低。与染铅组比较,硫胺素组肾组织FN蛋白的表达在喂饮3个月后显著下降,而mRNA的表达在喂饮2个月后即显著下降。结论硫胺素不仅有驱铅的作用,对铅所导致的肾脏纤维化也有一定的保护作用。

Objective To investigate the preventive effect of thiamine on experimental lead nephropathy, and its influence on the expression of fibronectin in kidney at molecular levels. Methods Seventy-two SD rats weighing 180 - 220 g were randomly assigned into three groups：control group, Pb group and Vb group. The rats in control group were given distilled water for 1,2,3 months respectively, the rats in Pb group were given 0.5 % lead acetate water for 1,2,3 months respectively, and the rats in Vb group were simultaneously given 0.5% lead acetate water and thiamine 3 mg/100 g body weight by intragastric administration for 1,2,3 months respectively. All rats were sacrificed at the end of the treatment. Lead concentrations in blood and kidney were determined by graphite furnace atomic absorption spectrometry. Expression of FN protein and mRNA in kidney was measured by immunohistochemistry and RT-PCR, respectively. Results Compared with Pb group, kidney lead concentrations decreased significantly after administration for 2 months in Vb group, and blood lead concentrations also decreased after administration for 3 months. The expression of FN protein was significantly lower in Vb group than in Pb group after administration for 3 months,while the expression of FN mRNA veas significantly lower in Vb group than in Pb group after administration for 2 months. Conclusion Thiamine can not only prevent accumulation of lead in the body, but also protect the lead-induced renal fibrosis.