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作 者:高双荣[1] 梁爱华[1] 戴宝强[1] 王丽芳[1] 李桂琴[1] 曹春雨[1] 刘婷[1] 李春英[1] 易艳[1] 王海林[1] 郝然[1] 赵雍[1] 回连强[1] 夏晶[2] 曹帅[2] 李丽敏[2] 季申[2]
机构地区:[1]中国中医科学院中药研究所,北京100700 [2]上海市食品药品检验所,上海201203
出 处:《中国实验方剂学杂志》2013年第18期297-301,共5页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家自然科学基金项目(81001692);国家"十一五"科技支撑计划项目(2006BAI55B02-03);国家科技重大专项(2009ZX09301005);中国中医科学院自主选题项目(ZZ03046)
摘 要:目的:研究反复灌胃给予雄黄后,大鼠肾脏毒性的病理形态学特征,为临床安全、有效地使用雄黄提供科学依据。方法:随机将大鼠分为对照组和雄黄0.01,0.04,0.17 g·kg-1剂量组。各剂量组均每日灌胃给药1次,对照组给予高纯水,连续3个月。于给药后1,2,3个月和停药1,2个月后,计算肾脏指数,测定血清葡萄糖(GLU)、肌酐(Cr)、尿素氮(BUN)及尿蛋白等,并观察肾组织病理形态学变化。结果:连续灌服雄黄≥0.01 g·kg-13个月或0.17 g·kg-12个月,肾组织出现不同程度的细胞肿胀,胞浆空泡变性,核固缩、溶解及血管扩张、充血等病变,近曲小管较肾小球损伤严重,病变呈现明显的量-时-毒关系,血BUN、GLU、尿蛋白也相应增高。停药1个月后,除0.17 g·kg-1剂量组有66.7%的肾小管轻度水肿、变性外,其余各组未见明显病变。结论:大鼠连续灌服雄黄≥0.01 g·kg-13个月或0.17 g·kg-12个月对大鼠肾脏病理学产生明显影响,尤其对肾脏近曲小管的损伤作用较为明显,停药后肾脏病变逐渐恢复至正常。Objective: To study the morphological characteristics of kidney toxicity in rats when repeated intra-gastric administration of realgar in order to provide a scientific basis for safe and effective application of realgar.Method: The rats were randomly divided into four groups: control group and realgar 0.01,0.04,0.17 g·kg-1groups.The rats were intra-gastrically treated with realgar once a day for successively 90 days,while the control group was given ultra-filtrated water.Calculatate the kidney weight and body weight index were calculated and the glucose,ketones,blood urine nitrogen and urine protein were measured and pathological change of kidney under microscope was observed at 30,60,90,120,150 days.Result: The kidney cells showed swelling,vacuolation,nuclear condensation,breakage,vasodilation and congestion after repeated intra-gastric administration of realgar ≥0.01 g·kg-1successively 90 days or 0.17 g·kg-1successively 60 days.Proximal convoluted tubules were seriously damaged.The lesions showed significant dose and time and toxicity relationship,blood urine nitrogen,glucose,urine protein also increased accordingly.66.7% of the renal tubular in 0.17 g·kg-1 group showed mild swelling and degeneration at day 30 after drug withdrawal,while the other groups had no significant lesions.Conclusion: Kidneys showed severe pathologic injuries after repeated intra-gastric administration of realgar≥0.01 g·kg-1successively 90 days or 0.17 g·kg-1successively 60 days.The proximal convoluted tubules may be a main target of arsenic toxicity to kidneys.The lesions can gradually restored to normal after realgar withdrawal.
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