二巯基丙磺酸钠对氯化汞中毒大鼠肾脏基因表达的影响

Effect of Sodium Dimercaptopropanesulfonate on Gene Expression of Kidney in Mercuric Chloride Treated Rats

[目的]运用基因芯片技术分析二巯基丙磺酸钠(DMPS)驱汞治疗对肾脏基因表达的影响,为进一步研究无机汞肾损伤及治疗的分子机制提供理论依据。[方法]健康雄性SD大鼠30只,随机分成3组,每组10只,阳性对照组和治疗组大鼠皮下注射氯化汞溶液建立亚慢性汞中毒肾脏损伤大鼠模型,阴性对照组大鼠皮下注射0.9%NaCl注射液,模型建好后治疗组大鼠肌肉注射DMPS驱汞治疗,阴性对照组和阳性对照组大鼠肌肉注射0.9%NaCl注射液,治疗结束后用基因芯片方法筛选大鼠肾脏差异表达基因,并用逆转录聚合酶链反应(RT-PCR)方法验证部分差异表达基因。[结果]阳性对照组与阴性对照组比较筛选出差异基因385个;治疗组与阴性对照组比较筛查出差异基因183个;治疗组与阳性对照组比较筛查出差异基因223个。DMPS治疗有效基因中明显差异表达基因23个,其功能涉及毒物、异物代谢,氧化应激应答,炎症应答,转录调节,离子转运和信号转导,细胞增殖与凋亡,胶原纤维、软骨的形成,神经递质代谢,糖类、脂类、氨基酸代谢等方面,并得到RT-PCR方法的验证。[结论]DMPS驱汞治疗可使汞中毒肾脏损伤差异基因得到明显恢复,这些明显恢复的基因可能在汞中毒肾脏损伤的发生和DMPS治疗中发挥重要作用。

[ Objective ] To explore the effect of sodium dimercaptopropanesulfonate （DMPS） on gene expression of kidney in HgCl2 treated rats by gene chips technology, and to provide theoretical basis for the molecular machinery of inorganic mercury- induced kidney injury and treatment. [ Methods ] Thirty SD male rats were randomly divided into 3 groups （10 each group）. An animal model of kidney injury was established by subcutaneous HgCl2 injection into the positive control group and the treatment group, and the negative control group was given 0.9% NaCl. Then the treatment group were intramuscularly injected with DMPS, the negative and the positive control groups were injected with 0.9% NaCl. After treatment, differentially expressed genes were identified by gene chips and validated by reverse transcription-polymerase chain reaction （RT-PCR）. [ Results ] A total of 385 genes were identified differentially expressed between the negative and the positive control groups; 183 between the negative control group and the treatment group; and 223 between the positive control group and the treatment group. Among the 23 genes expressed differentially involved in DMPS treatment, the functions included xenobiotic metabolism, oxidative stress response, inflammatory response, ion transport, signal transduction, transcription regulation, cell proliferation and apoptosis, collagen fibril organization and cartilage development, neurotransmitter metabolism, and lipid, glucose and amino acid metabolism, etc. Selected results were confirmed by RT-PCR. [ Conclusion ] DMPS can recover the differentially expressed genes of kidney induced by HgCl2, and these genes may possibly play an important role in kidney injury by mercury exposure and in subsequent DMPS treatment.