[关键词]
[摘要]
目的:研究柴胡醇提物对肝纤维化大鼠模型的保护作用及伴随毒副作用,为柴胡“功效—毒性”相关性研究提供实验数据。方法:通过给予高脂、酒精刺激和猪血清等造成大鼠肝纤维化模型,同时给予不同剂量的柴胡醇提物和阳性药,观察其在发挥药效作用时的伴随毒副作用,同时观察大鼠一般情况、体质量、日摄食量、日饮水量、证候积分,检测大鼠血中ALT、AST、HA、LN、IV-C、PCIII、TGF-β1、BUN、Cr指标的含量,计算主要脏器系数并进行病理组织学检查。结果:连续给予0.90-3.60g·kg-1的柴胡醇提物可改善大鼠饮食、饮水和活动情况,明显降低肝纤维化大鼠血中HA、LN、IV-C、PCIII等指标含量和肝脏系数,病理组织学改变减轻。但血ALT、AST水平出现柴胡高剂量反跳升高、血BUN、Cr水平增高。结论:柴胡醇提物可以明显改善大鼠肝纤维化程度,且量效关系良好,同时3.60g·kg-1的柴胡醇提物会产生一定的肝脏、肾脏的伴随毒副作用,尤其肝脏为重。
[Key word]
[Abstract]
In this study,the model of rats’liver fibrosis was established to examine the protective effect of alcohol extracts of B.chinense,which aimed to provide experimental evidence behind the relationship of its “toxicity-effect”.The model of rats’liver fibrosis was established through high-fat diet complicated with the administration of alcohol and porcine serum.Meanwhile,rats were respectively given several doses of alcohol extracts of B.chinense and positive medicine for observing their efficacy and assident toxicity.At the same time,general situation was observed,and body weight,daily appetite and water quantity,syndrome integral were measured.The contents of ALT,AST,HA,LN,IV-C,PCIII,TGF-β1,BUN and Cr in serum were tested while the organ indexes were measured and the major organs were scheduled for consideration by the pathology.As a result,giving alcohol extracts of B.chinense ranged from 0.90g·kg-1 to 3.60g·kg-1 for 21 consecutive days obviously improved the diet,drinking and physical activities of rats.The contents of ALT,AST,HA,LN,IV-C and PCIII and liver coefficient declined significantly,and liver fibrosis was also improved. However,the activities of ALT and AST in the high dose of B.chinense were higher than those of other dose groups,and the contents of BUN and Cr in serum increased. In conclusion,alcohol extracts of B.chinense presented an obviously effectiveness on liver fibrosis in rats and a good dose-effect relationship.At the same time,3.60g·kg-1,/sub> of B.chinense extracts had side effects and liver,kidney toxicity,especially in the liver.
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[基金项目]
国家自然科学基金委面上项目(81374059):柴胡肝毒性与功效、证候关系的基础研究,负责人:孙蓉;山东省科技厅自主创新和成果转化项目(2014ZZCX02104):药物安全性评价和适宜于抗肿瘤及缺血性脑血管疾病多靶点和复方新药成药性评价关键技术,负责人:孙蓉;山东省自然基金委重点项目(2011ZRB14333):SSa和SSd生物转化及基于功效的药理活性和肝毒性研究,负责人:孙蓉;山东省泰山学者工程专项经费资助,特聘专家(ts201511107):孙蓉。