运用基因芯片技术筛选亚慢性汞中毒大鼠肾脏差异表达基因

Screening with cDNA microarray on differential expression genes of kidney in rats injury induced by sub-chronic HgCl2 exposure

目的运用基因芯片技术分析亚慢性汞中毒大鼠肾脏基因表达谱的变化。方法健康雄性SD大鼠20只随机分成染毒组和对照组,每组10只。染毒组皮下注射0.2 mg/kg氯化汞溶液2个月,建立亚慢性汞中毒肾脏损伤大鼠模型,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。结果筛选出亚慢性汞中毒肾脏差异表达基因385个,其中上调139个,下调246个。上调基因主要涉及毒物异物应答、炎症应答、神经递质代谢、溶质体转运等功能;下调基因主要涉及基础物质代谢、细胞信号传导、免疫调节、细胞增殖、转录调节等功能基因。RT-PCR方法验证结果与芯片结果一致。结论汞中毒肾脏损伤是多基因参与的结果;筛选出的明显差异表达基因可能在肾脏损伤机制中发挥重要作用,可能是氯化汞肾脏毒性作用的敏感基因或靶基因。

Objective To investigate the expression profile of rat genes in response to sub-chronic mercuric chloride（HgCl2）exposure by gene chips technology.Methods 20 SD rats were randomly divided into 2 groups.Animal models of kidney injury were established by hypodermic injection of 0.2 mg/kg HgCl2 once daily for 2 months.The differential expression genes of kidney injury in rats were screened by gene chip technology,and then validated by RT-PCR.Results 385 genes were screened in the HgCl2 expose group with 139 genes up-regulated and 246 genes down-regulated.28 genes were observed having conspicuous differential expression,among which 10 genes up-regulated obviously involved in toxicant response,inflammatory response,solute transporter and neurotransmitter metabolism function,and 18 genes down-regulated obviously involved in lipid and glucose metabolism,signal transduction,immune response,cell differentiation and proliferation,transcription regulation function.The result of RT-PCR was coincident with those of gene chips.Conclusion Kidney injury induced by sub-chronic HgCl2 exposure is a unification of many genes,the 28 conspicuous differential expression genes possibly play important roles and may be the sensitive genes or target genes of HgCl2 kidney injury.