雷公藤甲素诱导小鼠急性肝损伤的形态学研究  

The Morphological Study on Acute Liver Injury of Mice Induced by Triptolide

作　　者：刘泽洲[1] 许可嘉 张天娇[1] 易小烈 赵福建[1] 杨美娟[1] 牛建昭[1] 李健[1] 

机构地区：[1]北京中医药大学基础医学院细胞生物化学实验室,北京100029 [2]贵州省黔西县中心医院,贵州毕节551500

出　　处：《现代生物医学进展》2015年第17期3207-3211,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81273884)

摘　　要：目的:观察雷公藤甲素诱导小鼠急性肝损伤的形态学特征,为进一步研究雷公藤甲素肝毒性的病理特点和毒理机制提供基础。方法:昆明种小鼠以雷公藤甲素LD50剂量(0.8 mg/kg)水溶液灌胃,分别于给药12 h及24 h后取肝组织,制备石蜡切片、冰冻切片,行常规HE染色、PCNA染色、TUNEL染色及光镜观察。部分肝组织经戊二醛固定、制备超薄切片,行透射电镜下观察。PCNA及TUNEL染色结果采用图像分析软件进行定量分析及统计学处理。结果:0.8 mg/kg雷公藤甲素灌胃后12 h即可诱导肝组织炎细胞浸润、结构破坏、肝细胞坏死及代偿性增生。透射电镜下可见肝细胞内细胞骨架结构异常、细胞器大量脱落、自噬体明显增多。PCNA及TUNEL染色结果表明,雷公藤甲素可诱导肝细胞出现显著的增殖及凋亡。结论:雷公藤甲素可诱导肝组织炎性反应发生,同时伴随肝细胞凋亡、坏死及代偿性增生。推测肝细胞自噬性凋亡是雷公藤甲素诱导急性肝损伤的关键病理环节。Objective： To observe the morphological characteristics of acute liver injury induced by triptolide in mice,and provide the basis of pathological characteristics and toxicological mechanisms of triptolide in liver for our further research. Methods： Kunming mice were given triptolide orally according to median lethal dose（LD50）, and dissected after 12 and 24 hours separately. Liver tissue were detected by HE, PCNA and TNUEL staining and transmission electron microscope. Then images were analyzed by image analysis software and the data was analyzed by statistical software. Result： After treated with 0.8 mg/kg of triptolide for 12 hours, liver tissue was inflamed and destroyed, hepatocyte necrosis and compensatory hypertrophy can be observed. The transmission electron microscope images show the cytoskeleton was abnormal, organelles were dropped and autophagosomes were increased. Conclusion： Triptolide can induce inflammatory reaction, accompanied by apoptosis, necrosis and compensatory hyperplasia in liver. We speculated that autophagic cell death induced by triptolide may be the key pathological factor for acute liver injury.

关 键 词：雷公藤甲素 小鼠 急性肝损伤 形态学 自噬性凋亡 

分 类 号：Q95-3[生物学—动物学] R285.5[医药卫生—中药学]