血人参活性提取部位对四氯化碳肝损伤的保护作用及机制研究  

Effects of ethyl acetate extracts from Indigofera stachyoides Radix against carbon tetrachloride induced liver injury in mice

作　　者：杨虹[1] 杨宇莎 彭芳[1] 刘杰[3] 吴芹[3] 郝小燕 时京珍[1] YANG Hong;YANG Yu-sha;PENG Fang;LIU Jie;WU Qin;HAO Xiao-yan;SHI Jing-zhen(Department of Basic Medical Sciences,Guiyang University of Chinese Medicine,Guiyang 550025,China;School of Pharmacy,Guizhou Medical University,Guiyang 550004,China;Key Laboratory of Basic Pharma-cology of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563099,China)

机构地区：[1]贵阳中医学院基础医学院,贵州贵阳550025 [2]贵州医科大学药学院,贵州贵阳550004 [3]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

出　　处：《时珍国医国药》2018年第10期2354-2357,共4页Lishizhen Medicine and Materia Medica Research

基　　金：贵州省科技合作计划项目(黔科合LH字[2016]7122号);国家自然科学基金(81460640)

摘　　要：目的筛选血人参保肝活性部位,确定血人参活性部位安全给药剂量,研究其对四氯化碳肝损伤的保护作用及机制。方法 (1)雄性小鼠随机分组,分别皮下注射给予梯度剂量100 mg·kg-1、200 mg·kg-1、400 mg·kg-1、800 mg·kg-1、1600mg·kg-1血人参乙酸乙酯提取物,给药后观察7天,记录小鼠一般情况,死亡情况。(2)分组给药剂量同前,连续给药4d,末次给药24h后,取小鼠血、肝脏,检测血清ALT、AST,肝脏病理。(3)雄性小鼠随机分组,模型组外,分别每日皮下注射给予乙酸乙酯提取物、石油醚提取物、正丁醇提取物、生药200mg·kg-1,等量生理盐水,连续给药4天,末次给药8h后腹腔注射0. 1%CCl4-菜油10 ml·kg-1,禁食16h,取小鼠血,检测ALT含量。(4)雄性小鼠随机分组,模型组外,分别每日皮下注射给予等量生理盐水、乙酸乙酯低剂量200 mg·kg-1、乙酸乙酯高剂量400 mg·kg-1,连续给药4天,造模方法同前,取小鼠血、肝组织,检测血清ALT、AST含量,肝组织GSH、MDA含量,肝组织病理,肝组织Nrf-2、HO-1、TNF-α、IL-1β、IL-6、Gadd45、Gadd153、BAD、BAX基因表达含量。结果各给药组小鼠急性毒性实验未见小鼠死亡,1600mg·kg-1连续给药四天可见转氨酶明显升高,伴随肝脏病理学改变,100 mg·kg-1、200 mg·kg-1、400 mg·kg-1、800 mg·kg-1给药剂量组未见明显肝脏毒性。血人参不同提取部位保肝结果显示乙酸乙酯部位能明显降低四氯化碳造成的谷丙转氨酶升高。与模型组比较,乙酸乙酯低高剂量均可明显降低血清ALT、AST含量,升高GSH含量,降低MDA含量,血人参低剂量组可升高Nrf2的表达,低高剂量组均可升高HO-1的表达,高剂量组可降低TNF-α基因的表达,低高剂量组均可降低IL-1β、IL-6、Gadd45、Gadd153、BAD、BAX基因的表达。结论血人参乙酸乙酯提取物具有良好的肝脏作用,其有效剂量未发现明显肝毒性,保肝作用机制与其影响抗氧化、抗炎、抑制细胞Objective To screen the main active fractions of Indigofera stachyoides Radix,and determine the protective effects against liver injury induced by carbon tetrachloride and security in mice. Methods 1. Male mice grouped randomly,administrated subcutaneous injection respectively with 100 mg·kg-1,200 mg·kg-1,400 mg·kg-1,800 mg·kg-1,1600 mg·kg-1 ethyl acetate extracts from Indigofera stachyoides Radix,observed general condition and death situation of mice for 7 days. 2. Male mice grouped randomly,administrated subcutaneous injection respectively with 100 mg·kg-1,200 mg·kg-1,400 mg·kg-1,800 mg·kg-1,1600 mg·kg-1 ethyl acetate extracts from Indigofera stachyoides Radix,daily for four days. The mice were sacrificed24 hours after the last infection and detected serum ALT,AST and liver histology. 3. Male mice grouped randomly,administrated subcutaneous injection respectively with saline,ethyl acetate extract,petroleum ether extract,n-butanol extract,crude drug daily for four days. 8 hours after the last infection,mice were intraperitoneally given 0. 1% CCl4(10 m L·kg-1 for 16 h),then examined serum ALT. 4. Male mice grouped randomly,administrated subcutaneous injection respectively with saline,100 mg ·kg-1,200 mg·kg-1 ethyl acetate extract,daily for four days. 8 hours after the last infection,mice were intraperitoneally given 0.1% CCl4(10 m L·kg-1 for 16 h),then examined serum ALT,AST,GSH,MDA,liver histology,gene expression related. Results Mice had no death in the experiment of acute toxicity. In 1600 mg·kg-1 group,ALT,AST increased obviously compared with normal group and had liver pathologic lesions. There was no liver lesions seen in other groups administrated with ethyl acetate extract. In the experiment of arbon tetrachloride induced liver injury,compared with model group,ethyl acetate extract could decreased ALT,AST,MDA,increased GSH,relieved liver pathologic lesions. Low-dose group increased the expression of Nrf2 mRNA,Low-dose and high-dose groups increased HO-1 mRNA expression and decreased the exp

关 键 词：血人参 保肝药 NRF2 TNF-Α 细胞凋亡 

分 类 号：R284[医药卫生—中药学]