自乳化给药系统对雷公藤甲素的减毒作用研究

Study on the Antitoxic Effect of Self-microemulsifying Drug Delivery System on Triptolide

关键词:  雷公藤甲素  自乳化给药系统  毒性

Key words:  triptolide  self-microemulsifying drug delivery system  toxicity

摘要:

目的 考察自乳化给药系统对雷公藤甲素的肝肾毒性影响。方法 构建荷人胃癌细胞株MGC80-3的裸鼠肿瘤模型，分为模型对照组、雷公藤甲素原料药组和雷公藤甲素自微乳组，灌胃给药，每2天1次，连续23 d，末次给药24 h后，各组裸鼠采血收集血清，检测各裸鼠血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）、尿素、肌酐、总蛋白、白蛋白、球蛋白及血尿酸；动物死亡后称重，解剖取肝、肾，观察形态，计算肝、肾指数；取各组裸鼠肝、肾组织病理切片，HE染色后，在生物显微镜下观察各组织形态学变化。结果 雷公藤甲素自微乳组与雷公藤甲素原料药组相比，给药后裸鼠血清AST和ALT极显著下降（P<0.01）；总蛋白显著升高（P<0.05），白、球蛋白比值极显著升高（P<0.01）；血肌酐有下降趋势，但无统计学意义；尿素显著下降（P<0.05）；尿酸极显著下降（P<0.01）。雷公藤甲素自微乳组肝细胞轻微肿胀，少见炎细胞灶状浸润；雷公藤甲素原料药组肝组织出现脂肪变形，肝细胞细胞核增大，碎片状坏死，中重度纤维化。2组动物的肾脏组织均无明显病理特征。结论 雷公藤甲素自微乳的肝肾毒性明显小于雷公藤甲素原料药。

Abstract:

OBJECTIVE To investigate the hepatotoxicity and renal toxicity of self-microemulsifying drug delivery system containing triptolide(TRL-SMEDDS) in mice.METHODS MGC80-3 human gastric tumor model in nude mice was constructed, and the mice were divided into model control group, triptolide(TRL) crude drug group and TRL-SMEDDS group. The mice were fed with saline, free TRL and TRL-SMEDDS, respectively, for once/2 days in 23 d. After 24 h of the last treatment, the serum of nude mice in each group were collected, and the level of ALT, AST, Urea, Scr, STP, ALB, GLOB and UA in serum were determined. The animals were weighed and the liver and kidney were also collected. The appearance and morphology of the liver and kidney were observed by the biological microscope after pathological section staining, and the liver and kidney index were calculated. RESULTS Compared with free TRL crude drug group, the level of AST and ALT in TRL-SMEDDS group was significantly declined(P<0.01), STP level was increased significantly(P<0.05), and A/G was also significantly rose (P<0.01). Scr level showed slightly decrease but had no statistical significance. Urea and UA level were decreased significantly(P<0.05 and <0.01, respectively). In TRL-SMEDDS group, liver cells were slightly swollen and a few inflammatory cells were found in liver tissue. In TRL crude drug group, some steatosis and fragmentation necrosis were showed in liver tissue. The hepatocyte nucleus obviously enlarged, and a large number of fibrous tissue was found. There were no obvious abnormal pathological features in renal tissue of both groups. CONCLUSION The TRL-SMEDDS presents a significantly decrease of hepatotoxicity and renal toxicity compared with free TRL.