中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
2期
243-247
,共5页
徐玉艳%张爱华%李军%陈黎媛%姚茂琳%于春%曾奇兵%何江
徐玉豔%張愛華%李軍%陳黎媛%姚茂琳%于春%曾奇兵%何江
서옥염%장애화%리군%진려원%요무림%우춘%증기병%하강
砷中毒%煤%肾损伤%生物学标志%基准剂量
砷中毒%煤%腎損傷%生物學標誌%基準劑量
신중독%매%신손상%생물학표지%기준제량
arsenic poisoning%coal%kidney da mage%bio markers%bench mark dose
目的:观察燃煤型砷中毒大鼠肾毒性作用,应用基准剂量(BMD)法探讨肾功能效应标志改变的尿砷(UAs)的基准剂量。方法Wistar 大鼠连续90 d 喂饲砷25,50,100 mg·kg -1污染饲料。检测大鼠UAs、肾砷(KAs)及肾功能指标并观察肾常规病理学及其纤维化改变。以 UAs 为暴露标志,尿β2-微球蛋白微球蛋白(Uβ2-MG)、尿 N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)及尿白蛋白(UALB)为效应标志,运用 BMD法计算各效应标志对应的 UAs 的 BMD 及其基准剂量95%可信限下限 BMDL。结果砷100 mg·kg -1组大鼠 UAs,KAs,UALB,UNAG,Uβ2-MG 含量均高于正常对照组(P <0.05);光镜下各染砷组大鼠肾 HE染色可见炎性细胞浸润、肾小管上皮细胞肿胀、肾间质毛细管扩张、充血等不同程度的病理学改变,Masson染色可见肾小管间质不同程度的纤维化;以 UAs 为暴露标志,Uβ2-MG,UNAG,UALB 为效应标志,计算得出各效应标志 UAs 的 BMD 分别为998.9,1213.5和1386.9μg·g -1 Cr,BMDL 分别为660.5,803.6和909.4μg·g -1 Cr。燃煤型砷中毒大鼠肾功能早期改变的尿砷的 BMD 及 BMDL 分别为998.9和660.5μg·g -1 Cr。结论微小病变型肾病可能是燃煤砷污染对肾损害的主要病理类型,推荐使用较为敏感的生物学标志Uβ2-MG来估算砷致肾损伤的生物暴露限值。
目的:觀察燃煤型砷中毒大鼠腎毒性作用,應用基準劑量(BMD)法探討腎功能效應標誌改變的尿砷(UAs)的基準劑量。方法Wistar 大鼠連續90 d 餵飼砷25,50,100 mg·kg -1汙染飼料。檢測大鼠UAs、腎砷(KAs)及腎功能指標併觀察腎常規病理學及其纖維化改變。以 UAs 為暴露標誌,尿β2-微毬蛋白微毬蛋白(Uβ2-MG)、尿 N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)及尿白蛋白(UALB)為效應標誌,運用 BMD法計算各效應標誌對應的 UAs 的 BMD 及其基準劑量95%可信限下限 BMDL。結果砷100 mg·kg -1組大鼠 UAs,KAs,UALB,UNAG,Uβ2-MG 含量均高于正常對照組(P <0.05);光鏡下各染砷組大鼠腎 HE染色可見炎性細胞浸潤、腎小管上皮細胞腫脹、腎間質毛細管擴張、充血等不同程度的病理學改變,Masson染色可見腎小管間質不同程度的纖維化;以 UAs 為暴露標誌,Uβ2-MG,UNAG,UALB 為效應標誌,計算得齣各效應標誌 UAs 的 BMD 分彆為998.9,1213.5和1386.9μg·g -1 Cr,BMDL 分彆為660.5,803.6和909.4μg·g -1 Cr。燃煤型砷中毒大鼠腎功能早期改變的尿砷的 BMD 及 BMDL 分彆為998.9和660.5μg·g -1 Cr。結論微小病變型腎病可能是燃煤砷汙染對腎損害的主要病理類型,推薦使用較為敏感的生物學標誌Uβ2-MG來估算砷緻腎損傷的生物暴露限值。
목적:관찰연매형신중독대서신독성작용,응용기준제량(BMD)법탐토신공능효응표지개변적뇨신(UAs)적기준제량。방법Wistar 대서련속90 d 위사신25,50,100 mg·kg -1오염사료。검측대서UAs、신신(KAs)급신공능지표병관찰신상규병이학급기섬유화개변。이 UAs 위폭로표지,뇨β2-미구단백미구단백(Uβ2-MG)、뇨 N-을선-β-D-안기포도당감매(UNAG)급뇨백단백(UALB)위효응표지,운용 BMD법계산각효응표지대응적 UAs 적 BMD 급기기준제량95%가신한하한 BMDL。결과신100 mg·kg -1조대서 UAs,KAs,UALB,UNAG,Uβ2-MG 함량균고우정상대조조(P <0.05);광경하각염신조대서신 HE염색가견염성세포침윤、신소관상피세포종창、신간질모세관확장、충혈등불동정도적병이학개변,Masson염색가견신소관간질불동정도적섬유화;이 UAs 위폭로표지,Uβ2-MG,UNAG,UALB 위효응표지,계산득출각효응표지 UAs 적 BMD 분별위998.9,1213.5화1386.9μg·g -1 Cr,BMDL 분별위660.5,803.6화909.4μg·g -1 Cr。연매형신중독대서신공능조기개변적뇨신적 BMD 급 BMDL 분별위998.9화660.5μg·g -1 Cr。결론미소병변형신병가능시연매신오염대신손해적주요병리류형,추천사용교위민감적생물학표지Uβ2-MG래고산신치신손상적생물폭로한치。
OBJECTIVE Study the kidney toxic effects caused by burning coal endemic arsenism in rats,application bench mark dose (BMD) method to investigate the bench mark dose of urinary arsenic (UAs)and the changes in bio markers of renal function.METHODS Wistar rats were fed for 90 d with arsenic 0,25,50,100 mg·kg -1 conta minated feed.Urinary arsenic,kidney arsenic and renal function indicators were determined,and routine pathological and fibrosis of kidney were exa mined.UAs as the exposure bio marker,Uβ2-MG,UNAG and UALB for the effect bio markers,application bench mark dose method to calculate the BMD and BMDL of UAs for each effect bio markers.RESULTS UAs,KAs, Uβ2-MG,UNAG,UALB levels of rats in arsenic 100 mg·kg -1 group were increased than normal group (P <0.05);In light microscope,the results of HE staining of rat kidney in all arsenic dose groups showed infla mmatory cell infiltration,renal tubular epithelial cell swelling,renal interstitial capillary dila-tion,congestion and other varying degrees pathological changes,and the results of masson staining showed varying degrees of tubulointerstitial fibrosis;UAs as the exposure bio marker,Uβ2-MG,UNAG, UALB for the effects of mark,the BMD and BMDL of UAs for Uβ2-MG,UNAG,UALB were calculated, the BMD values were 998.9,1213.5,1386.9 μg·g -1 Cr,the BMDL values were 660.5,803.6 and 909. 4 μg·g -1 Cr,respectively.CONCLUSION Burning coal arsenic pollution can cause kidney da mage in rats,mini mal change nephropathy may be the pri mary pathological in the coal arsenic conta mination of kidney da mage.The BMD and BMDL of UAs were 998.9,660.5 μg·g -1 Cr,the early changes of renal function of burning coal arsenism in rats;it is reco mmended to use the more sensitive bio markers Uβ2-MG to calculate the biological exposure li mits on renal injury caused by arsenic.