比较佐太、朱砂与汞化合物对胎、幼、孕和老年鼠的肾脏毒性  

Comparative study of Zuotai and Zhusha with HgCl_2 and Me Hg on kidney injury in fetal,dam,weanling and aged rats

作　　者：李文楷[1] 侯玮钰 吴青[2] 罗娅[3] 岑语燕 陆远富[1] 刘杰[1] 魏立新[4] 

机构地区：[1]遵义医学院基础药理省部共建教育部重点实验室,贵州遵义563099 [2]遵义医学院药学院,贵州遵义563099 [3]遵义医学院公共卫生学院,贵州遵义563099 [4]中国科学院西北高原生物研究所藏药研究重点实验室,青海西宁810001

出　　处：《遵义医学院学报》2016年第2期129-133,共5页Journal of Zunyi Medical University

基　　金：国家"十二五"科技支撑计划资助项目(NO:2012BAI27B05);国家自然科学基金资助项目(NO:81460632);贵州省研究生教育创新基地项目(NO:黔教科2008-02)

摘　　要：目的比较佐太、朱砂和汞化合物对胎、幼、孕和老年鼠的肾毒性。方法采用孕19 d的胎鼠、母孕鼠、刚断奶的幼鼠和15月的老年鼠(均为SD大鼠),口服给于藏药佐太(30 mg/kg)、朱砂(Hg S,30 mg/kg),以及等汞量的氯化汞(Hg Cl_2,33.6 mg/kg)和1/10等汞量的甲基汞(Me Hg,3.1 mg/kg),连续7 d,观察动物的体重和一般情况,末次给药24 h后取肾脏,观察肾病理改变、肾汞蓄积和肾脏中肾损伤因子Kim-1 mRNA的表达。结果连续给予佐太和朱砂7 d后,大鼠未见明显异常,而氯化汞组体重明显下降(P<0.05)。氯化汞引起明显肾汞蓄积,甲基汞组大鼠也有所升高。而佐太组和朱砂组仅轻微增加。母孕鼠和老年鼠氯化汞组的肾损伤尤为明显,甲基汞组也出现肾损伤,而佐太和朱砂未见明显肾病理改变。肾脏毒性敏感基因Kim-1的表达表明,氯化汞组Kim-1的表达显著升高(P<0.05),只有Hg S 1/10等汞量的甲基汞也有所升高,而佐太和朱砂与对照组无明显差异。胎鼠对汞毒性不敏感,幼鼠轻度敏感,母孕鼠中度敏感,而老年鼠显著敏感。结论在等汞量的基础上,藏药佐太和朱砂的肾毒性远小于氯化汞和1/10等汞量的甲基汞;汞化合物的毒性随鼠年龄而异,胎鼠和幼鼠不敏感,成年孕鼠尤其老年鼠易受汞所致的肾毒性。Objective To compare the renal toxicity of the Tibetan medicine Zuotai and Chinese medicine Zhusha（ Hg S） with mercury chloride（ HgCl2） and methylmercury（ MeHg） in various ages from fetal（- 2 d before born）,weanling（ 21 d- old）,dam（ 3 mo- old）,and aged（ 15 mo- old） rats. Methods Rats were orally administered with Zuotai（ 30 mg / kg）,Zhusha（ Hg S,30 mg / kg）,Hg Cl2（ 33. 6 mg /kg,equal Hg content of Hg S）,and Me Hg（ 3. 1 mg / kg,1 /10 Hg content of Hg S） for 7 days. The body weight and the general health were observed. At the termination of the experiments,kidney pathology,renal Hg accumulation,and the expression of kidney injury molecule- 1（ Kim- 1） were examined. Results Repeated administration of Zuotai and Zhusha did not show abnormalities in all age groups,while HgCl2 retarded body weight in weanling rats and decreased body weight in aged rats and Me Hg slightly decreased rat body weight. Significant Hg accumulation was observed after HgCl2 treatment,and to a lesser extent after Me Hg treatment,but renal Hg content was only slightly increased in Zuotai and Zhusha groups. Histologically,HgCl2 produced obviously renal injury and Me Hg produced mild renal injury,while no apparent pathology was evident after Zuotai and Zhusha treatment. The expression of Kim- 1 was dramatically increased after HgCl2 treatment,followed by Me Hg,especially in the aged rats and dam rats. In weanling rats and fetal rats,the expression of Kim- 1 was not significantly affected.Conclusion Zuotai and Zhusha are much less nephrotoxic than HgCl2 and Me Hg. Fetal rats and weanling rats are less sensitive to Hg toxicity,and the aged rats are sensitive to mercury toxicity.

关 键 词：藏药佐太 Hg S HgCl2 MeHg 肾毒性 肾汞 肾损伤因子1(Kim-1) 

分 类 号：R595.2[医药卫生—内科学] R961.1[医药卫生—临床医学]