摘要
目的:初步探讨长期给予藏药"佐太"对大鼠肾脏可能存在的潜在损伤,以期揭示其长期用药对肾脏可能存在的潜在毒性作用机制,为"佐太"制剂在临床上的安全合理使用提供一定的实验依据。方法:将80只SD大鼠随机分为空白对照组和藏药"佐太"66.70mg/kg、33.35 mg/kg、16.68 mg/kg剂量组,通过对大鼠给予"佐太"混悬液180天和停药恢复30天,对动物进行一般观察,检测大鼠肾脏中肾损伤因子1(Kim-1)和金属硫蛋白(MT)含量及Kim-1和MT-1 mRNA表达水平。结果:连续给药"佐太"180天和停药30天后,藏药"佐太"各给药组大鼠一般外观行为体征均无明显异常,各给药组大鼠肾脏中Kim-1和MT含量与空白组比较均无明显差异。而给药180天后,与空白组比较,33.35 mg/kg、16.68 mg/kg剂量组大鼠肾脏中Kim-1 mRNA表达水平均显著升高,66.70mg/kg、33.35 mg/kg、16.68 mg/kg剂量组大鼠肾脏中MT-1 mRNA表达水平均显著升高,停药30天后二者均恢复至与空白对照组无差异。结论:推测长期大剂量使用藏药"佐太"可能引起肾脏潜在的可逆性损伤,该损伤机制可能与升高Kim-1和MT的mRNA表达水平密切相关。藏药"佐太"的安全性问题仍然需要广泛而深入地研究。
Objective： To preliminarily investigate the possible potential damage and the potential nephrotoxicity mechanism of long-term medication of Tibetan medicine ＂Tsothel＂ on kidney of rats and provide certain theoretical basis for safe and rational use of ＂Tsothel＂ in clinic. Meth- ods： 80 SD rats were randomly divided into normal group and Tibetan medicine ＂Tsothel＂ groups involving 66.70mg/kg,33.35 mg/kg, 16. 68 mg/kg dose. The rates were observed general daily signs, content of kidney injury molecule-1 （Kim-1） and metallothionein （MT）, Kim- 1 mRNA expression level and MT-1 mRNA expression level at 180d after medication and at 30d after drug discontinuance, respectively. Re- suits： There was no obvious behavior disorder of the rats at 180d after continuous drug application and at 30d after drug discontinuance, and there was no obvious difference in Kim-1 and MT between black control group and Tibetan medicine ＂Tsothel＂ group（ P 〉 0.05. However, 180 days after the rats were given with drug, Kim-1 mRNA expression level in the kidney of the 33.35 mg/kg and 16.68 mg/kg groups with went up obviously （ P 〈 0.05 or P 〈 0.01 ）, as well as MT-1 mRNA expression level of the dosage groups with 66.70mg/kg, 33.35 mg/kg and 16.68 mg/kg. 30 days after the drug discontinuance, both of them recovered. Conclusions： It is speculated that the long-term medication of ＂Tsothel＂ may lead to potential reversible renal injury. This damage mechanism may have close relationship with Kim-1 and MT. The safety problem of Tsothel still requires wide and deep research.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2014年第6期154-158,共5页
Pharmacology and Clinics of Chinese Materia Medica
基金
"十二五"国家科技支撑计划项目(项目编号:2012BAI27B05-2)
四川省科技厅省青年科技创新研究团队专项计划项目(2014TD0007)
