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 mg/kg）组，单独何首乌（生药2.16 g/kg）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 g/kg）+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2.16 g/kg）+阳性药联苯双酯（2 mg/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2 d，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iv LPS，给予LPS 7 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 hepatotoxicity. 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, and1.6 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 collected. HE staining was used to observe the pathological changes of liver tissue, and the contents of ALT, AST, TNF-α, IL-1β, 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-κB 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-κB p65, and decrease plasma TNF-α and other inflammatory cytokines. Conclusion Liuweiwuling Tablets can reduce inflammation through the inhibition of NF-κB signaling pathway, and prevent of PM induced idiosyncratic liver injury.

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