蛋白激酶Cδ对燃煤污染型砷中毒肝损伤的调控机制  

The regulation mechanism of protein kinase Cδ on arsenic liver injury caused by coal-burning

作　　者：胡勇[1] 张爱华[1] 姚茂琳[1] 唐旭东 黄晓欣 

机构地区：[1]贵阳医学院毒理学教研室,550004 [2]解放军第四十四医院内科

出　　处：《中华预防医学杂志》2013年第9期777-782,共6页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金（81172603）;贵州省科技厅基金（黔科合重大专项20066016、黔科合J20122044）

摘　　要：目的 探讨蛋白激酶Cδ（protein kinase C8,PKCδ） mRNA转录和蛋白表达在燃煤型砷中毒肝损伤中的作用.方法 人群研究：选取符合条件的贵州省燃煤污染型砷中毒病区133例砷暴露者纳入砷暴露组,包括病区非病例组（25例）、无明显肝病组（38例）、轻度（43例）和中重度（27例）肝病组；选取非砷污染村34名健康居民纳入对照组.采集上述研究对象的尿液和外周血,测定尿砷含量及外周血PKCδ mRNA表达水平.动物实验：采用随机数字表法将30只Wistar大鼠分为对照组、饮水型砷中毒组和燃煤污染型砷中毒组（即低、中、高砷粮食污染组）,每组6只.对照组常规喂养,饮水型砷中毒组给予10 mg/kg As2O3水溶液,燃煤污染型砷中毒组喂饲用病区高砷煤烘烤的玉米粉所配制的饲料（砷含量分别为25、50和100 mg/kg）,均喂养3个月.测定其尿砷含量、外周血和肝组织PKCδ mRNA表达水平及肝组织磷酸化蛋白激酶C8 （phosphorylated protein kinase C8,pPKCδ）表达水平.结果 非病例组、无明显肝病组、轻度和中重度肝病组尿砷含量中位数（四分位数）分别为25.58（18.62 ～ 40.73）、56.66（38.93 ～ 76.77）、64.90（39.55 ～98.37）和75.47（41.30～109.70） μg/g肌酐,除病区非病例组外,其余组均高于对照组[23.34（17.84～37.45） μg/g肌酐]（P值均＜0.05）.大鼠饮水型砷中毒组和低、中、高砷粮食污染组尿砷含量分别为2223.61（472.98～3976.73）、701.16（194.01～1300.27）、1060.94（246.33～2585.47）和3101.11 （1919.97～5407.07） μg/g肌酐,均高于对照组[94.32（22.65 ～ 195.25） μg/g肌酐]（P值均＜0.05）；肝组织中pPKCδ蛋白表达水平分别为324.83±25.06、278.50±30.57、308.83±34.67、326.33±35.09,均高于对照组（240.17±28.07）（P值均＜0.05）；肝组织细胞膜中pPKCδ蛋白表达水平分别为0.49±0.06、0.33±0.05、0.37±0.06、0.50±0.08,均高于对照组（0.28±0.04）�Objective To investigate the effects of mRNA transcriptional and protein expressions of protein kinase Cδ （PKCδ） on the development of arsenic liver injury caused by coal-burning.Methods Population study：133 arsenic exposures were selected as arsenic exposure groups including the ward nonpatient group（25 cases）,no obvious hepatopathy group（38 cases）,mild （43 cases）and moderate to severe hepatopathy group（27 cases）from the area with endemic arsenism in Guizhou province.Another 34 healthy residents were selected as the control group in non-arsenic pollution village.The urine and peripheral blood were collected from the subjects.The arsenic contents in urine and mRNA expressions of PKCδ in peripheral blood were detected.Animal experiment study：thirty wistar rats were randomly by random number tabledivided into control group,drinking water arsenic poisoning group and coal-burning arsenic poisoning group （i.e.,low,medium and high arsenic contaminated grain group） by random number table method,including 6 rats in each group.The control group was fed normally for 3 months,drinking water arsenic poisoning group and coal-burning arsenic poisoning groups were fed respectively with 10 mg/kg As2O3 solution and different concentrations （25,50 and 100 mg/kg） of arsenic-containing feed which was persisted 3 months.The arsenic contents in urine,mRNA expression levels of PKCδ in peripheral blood and liver tissue and the protein expression levels of phosphorylated protein kinase C8（pPKCδ） in liver tissue were detected.Results The median （quartile） of arsenic contents in urine were 25.58 （18.62-40.73）,56.66 （38.93-76.77）,64.90 （39.55-98.37） and 75.47（41.30-109.70） μg/g Cr respectively for the non-patient group,no obvious hepatopathy group,mild and moderate to severe hepatopathy group.The levels were higher than that in the control group （23.34 （17.84-37.45） μg/g Cr） （P ＜ 0.05）,except for the ward non-patient group.The arsenic contents in rat urine were 222

关 键 词：砷中毒 煤 蛋白激酶Cδ 肝损伤 

分 类 号：R599[医药卫生—内科学]