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  本文關鍵詞： 鎘 DNA甲基化 Tet酶 肝功能 腎功能 小鼠　出處：《環(huán)境與職業(yè)醫(yī)學》2015年05期 　論文類型：期刊論文

【摘要】：[目的]初步探討氯化鎘(cadmium chloride,Cd Cl2)亞急性暴露(4周染毒)對小鼠肝腎功能、全基因組甲基化水平及去甲基化酶Tet1表達的影響。[方法]將48只SPF級KM小鼠(昆明小鼠,雌雄各半)隨機分為4組:對照組(dd H2O)、Cd Cl2 17.5 mg/kg組、25 mg/kg組、35 mg/kg組。經口灌胃染毒(每天1次、每周5 d),共染毒4周,CO2麻醉法處死動物。測定肝臟和腎臟的臟器系數(shù)、血液常規(guī)及血液生化檢查、肝腎組織病理學檢查、全基因組DNA甲基化水平及Tet1酶表達水平。[結果]35 mg/kg染毒組小鼠活動度及精神狀態(tài)較差。小鼠體重在各染毒周期和染毒劑量組間差異均有統(tǒng)計學意義,且存在交互作用(P0.05)。與對照組相比,雄性小鼠肝臟質量和肝臟臟器系數(shù)在25 mg/kg和35 mg/kg劑量組差異具有統(tǒng)計學意義(P0.05);血液常規(guī)檢查結果顯示,雌、雄性小鼠35 mg/kg染毒組血液白細胞(WBC)、血小板(PLT)、淋巴細胞(LYM)計數(shù),均高于對照組(P0.05);雄性小鼠在各個染毒劑量組間,WBC、PLT、LYM、RBC計數(shù)差異有統(tǒng)計學意義(P0.05)。此外,血生化實驗結果顯示,各劑量組雄性和雌性小鼠中肝功能的主要指標谷丙轉氨酶(ALT)、堿性磷酸酶(ALP)差異有統(tǒng)計學意義(P0.05),腎功能的主要指標尿酸(UA)、血尿素氮(BUN)、肌酐(CR)差異均有統(tǒng)計學意義(P0.05)。組織病理學分析發(fā)現(xiàn)25 mg/kg和35 mg/kg組雄性小鼠肝臟及腎臟呈現(xiàn)明顯的病理性改變。Tet1 m RNA及其蛋白表達水平僅在雄性小鼠的肝臟、腎臟中表達的差異有統(tǒng)計學意義(P0.05)。焦磷酸測序結果顯示,雄性小鼠肝臟、腎臟甲基化水平表達差異有統(tǒng)計學意義(P0.05),且其與Tet1 m RNA表達呈負相關(r=-0.473,P0.05;r=-0.134,P0.05)。[結論]Cd Cl2亞急性染毒可以誘導小鼠肝腎功能損傷,且對全基因組甲基化水平和去甲基化酶Tet1表達呈現(xiàn)出性別差異影響,雄性小鼠的肝腎組織Tet1表達參與調控全基因組DNA甲基化水平改變。
[Abstract]:[Objective] to study the effects of cadmium chloride on liver and kidney function of mice after subacute exposure to cadmium chloride (CDCL _ 2) for 4 weeks. Effect of genomic methylation level and Tet1 expression of demethylase. [Methods] 48 km mice of SPF grade (Kunming mice, half male and half female) were randomly divided into 4 groups: the control group was treated with CD Cl2 17.5 mg/kg. The animals in 25 mg/kg group were given intragastric administration (5 days a week, once a day, 5 days a week). The animals were killed by CO _ 2 anesthesia for 4 weeks. The organ coefficients of liver and kidney were measured. Blood routine and blood biochemical examination, liver and kidney histopathology, whole genome DNA methylation level and Tet1 enzyme expression level. [Results: the activity and mental state of the mice in the 35 mg/kg group were poor, and the weight of the mice was significantly different in the different exposure cycles and dose groups. And there was interaction between the two groups (P 0.05), compared with the control group. The difference of liver mass and liver organ coefficient between 25 mg/kg and 35 mg/kg group was statistically significant (P 0.05). The results of routine blood examination showed that WBC, PLT, and LYM were found in 35 mg/kg infected group of female and male mice. All of them were higher than the control group (P 0.05). There was significant difference in RBC count between different dose groups of male mice. In addition, the results of blood biochemistry test showed that the RBC counts of LYMN were significantly different among different dose groups. The main indexes of liver function in male and female mice were alanine aminotransferase (alt) and alkaline phosphatase (ALP). The main indexes of renal function were UAA, bun (bun). There were significant differences in creatinine creatinine (creatinine) (P 0.05). Histopathological analysis showed that the liver and kidney of 25 mg/kg and 35 mg/kg mice showed obvious pathological changes. The expression of RNA and its protein was found only in the liver of male mice. The difference in the expression of methylation in the kidney was statistically significant (P 0.05). The results of pyrosequencing showed that the expression of methylation in the liver and kidney of male mice was significantly different (P 0.05). And it was negatively correlated with the expression of Tet1 m RNA (P 0.05). R-0.134, P0.05. [Conclusion CD Cl2 subacute exposure can induce liver and kidney function injury in mice, and has a gender difference on the whole genome methylation level and the expression of demethylase Tet1. The expression of Tet1 in the liver and kidney of male mice is involved in the regulation of genomic DNA methylation.
【作者單位】： 中山大學公共衛(wèi)生學院預防醫(yī)學系;廣州市疾病預防控制中心毒理學檢驗部;
【基金】：國家自然科學基金(編號:81101562,81273099) 中央高校基本科研基金(編號:12ykpy13) 廣東省自然科學基金(編號:s2012010009633) 廣東省科技計劃項目(編號:2012b060300005)
【分類號】：R114
【正文快照】： 鎘(cadmium,Cd)及其化合物是多種工業(yè)生產中廣泛應用的原料,1993年國際癌癥研究中心(International Agency for Research on Cancer,IARC)及美國國家毒理學計劃署(US National ToxicologyProgram)將其列為人類確定致癌物[1-2]。Cd也是一種潛在的致突變劑[3];可在哺乳動物細胞

【參考文獻】

相關期刊論文 前1條

1 吳訓偉,金泰^，

本文編號：1471209