基于免疫调控的六味五灵片对何首乌致大鼠特异质肝损伤的防治作用  

Protective effect of Liuweiwuling Tablets on idiosyncratic liver injury induced by Polygonum multiflorum in rats based on immunomodulation

作　　者：贺兰芝 孟雅坤 张振芳[2] 韩延忠 王亚[2] 伍珊娜 孙小茗[2] 肖小河[2] 王伽伯[2] 柏兆方[2] HE Lan-zhi MENG Ya-kun ZHANG Zhen-fang HAN Yan-zhong WANG Ya Wu Shan-na SUN Xiao-ming XIAO Xiao-he WANG Jia-bo BAI Zhao-fang(School of Pharmacy, Hunan University of Traditional Chinese Medicine, Changsha 410208, China China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]解放军第三0二医院全军中医药研究所,北京100039 [3]江西中医药大学药学院,江西南昌330004

出　　处：《中草药》2017年第1期136-142,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金青年基金(81503350);国家“重大新药创制”科技重大专项课题(2015ZX09501-004-001-008);国家公益性行业科研专项课题(201507004-04);2015年度国家中医临床研究基地业务建设第二批科研专项(JDZX2015188);中药资源系统研究与开发利用省部共建国家重点实验室培育基地开放研究基金资助项目

摘　　要：目的基于内毒素脂多糖(LPS)模型,探讨六味五灵片对何首乌致大鼠特异质肝损伤的防治作用。方法将80只SD大鼠随机分为对照组,LPS(2.8 mgNg)组,单独何首乌(生药2.16 gNg)组,LPS(2.8 mg/kg)+何首乌(生药2.16 g/kg)组,LPS(2.8 mg/kg)+何首乌(生药2.16 gNg)+六味五灵片低、中、高剂量(0.4、0.8、1.6 g/kg)组及LPS(2.8 mg/kg)+何首乌(生药2.16g/kg)+阳性药联苯双酯(2mg/kg)组。按组别分别ig给予相应剂量的六味五灵片和联苯双酯,每日1次,连续给药2d,第3天除对照组和LPS组ig等量蒸馏水外,按组别分别ig给予何首乌醇提物,3 h后按组别尾ivLPS,给予LPS7 h后戊巴比妥钠麻醉大鼠,下腔静脉取血并采集肝组织标本。比色法检测血浆中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST),HE染色观察肝组织病理学变化,TUNEL检测分析肝细胞凋亡,ELISA法检测血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、γ干扰素(IFN-γ)水平,免疫组化染色观察肝组织核转录因子-κB(NF-κB)p65的表达。结果六味五灵片能明显降低何首乌诱导的特异质肝损伤大鼠血浆中ALT和AST水平(P<0.05),减轻肝组织病理损伤和肝细胞凋亡,明显抑制NF-κB p65的表达(P<0.05),同时明显降低血浆中TNF-α等炎症因子水平(P<0.05、0.01)。结论六味五灵片可通过抑制NF-κB信号通路,减轻炎症反应,防治何首乌诱发的特异质肝损伤。Objective To investigate the protective effect of Liuweiwuling Tablets of Polygonum multiflorum （PM）-induced idiosyncratic bepatotoxicity. Methods Eighty Sprague-Dawley （SD） rats were randomly divided into control group, LPS group, PM group, LPS ＋ PM group, LPS ＋ PM ＋ Liuweiwuling Tablets low, medium, and high dose （0.4, 0.8, andl.6 g/kg） groups, and LPS ＋ PM ＋ positive drug Biphenyl group （2 mg/kg）. All groups were orally given Liuweiwuling Tablets and Biphenyl once daily for consecutive 2 d according to the different dosages. On day 3, except the normal group and LPS group oral administration of distilled water, all groups were given PM （crude drug 2.16 g/kg）, 3 h after the group by the tail vein injection LPS （2.8 mg/kg） according to the different dosage; After 7 h, the rats were anesthetized with sodium pentobarbital, and the inferior vena cava was used to collect blood and liver tissue samples were co llected. HE staining was used to observe the pathological changes of liver tissue, and the contents of ALT, AST, TNF-α, IL-115, IL-6, and IFN-γ in rat plasma were determined. TUNEL assay analyzed hepatocyte apoptosis, and immunohistochemical staining was performed to detect the liver tissue expression activity of NF-rd3 p65. Results Liuweiwuling Tablets could decrease ALT and AST levels of PM-induced idiosyncratic liver injury rat plasma, reduce liver pathological injury and hepatocyte apoptosis, inhibit the expression of NF-rd3 p65, and decrease plasma TNF-αand other inflammatory cytokines. Conelusion Liuweiwuling Tablets can reduce inflammation through the inhibition of NF-κB signaling pathway, and prevent of PM induced idiosyncratic liver injury.

关 键 词：六味五灵片 何首乌 特异质肝损伤 脂多糖 核转录因子-κB信号通路 

分 类 号：R285.5[医药卫生—中药学]