论文部分内容阅读
[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 analyze the effect of DMPS-treated mercury on gene expression in kidney using gene chip technology, and provide a theoretical basis for further study on the molecular mechanism of inorganic mercury-induced kidney injury. [Methods] Thirty healthy male Sprague-Dawley rats were randomly divided into three groups with 10 rats in each group. The rats in the positive control group and the treatment group were subcutaneously injected with mercuric chloride solution to establish a rat model of renal damage induced by subchronic mercury poisoning. The negative control group Rats were subcutaneously injected with 0.9% NaCl injection. After the model was established, rats in the treatment group were intramuscularly injected with DMPS, and negative control group and positive control group were injected with 0.9% NaCl intramuscularly. After the treatment, gene chips were used to screen large Mouse kidney differentially expressed genes, and reverse transcription polymerase chain reaction (RT-PCR) method to verify some of the differentially expressed genes. [Results] A total of 385 differentially expressed genes were screened out in the positive control group and the negative control group. 183 differential genes were screened in the treatment group and the negative control group. 223 differential genes were screened in the treatment group and the positive control group. Twenty-three genes were significantly differentially expressed in DMPS-treated and their functions were related to toxicants, foreign body metabolism, oxidative stress response, inflammatory response, transcriptional regulation, ion transport and signal transduction, cell proliferation and apoptosis, collagen fibers and cartilage formation , Neurotransmitter metabolism, carbohydrates, lipids, amino acid metabolism and other aspects, and by RT-PCR method validation. [Conclusion] Mercury-treated DMPS can significantly restore the differentially expressed genes in kidney of mercury poisoning, and these obviously recovered genes may play an important role in the pathogenesis of mercury poisoning and DMPS treatment.