山茱萸总苷对小鼠免疫性肝损伤治疗作用的初步研究

Preliminary study on the effect of total glycosides from Cornus Officinalis on treatment of acute immunologic liver injury induced by ConA in mice

[目的]研究山茱萸总苷(TGCO)对刀豆蛋白A(ConA)诱导的小鼠急性免疫性肝损伤的治疗作用及其机制。[方法]C57BL小鼠60只,随机分为正常对照组、模型组、TGCO高、中、低剂量组(920、460、230 mg/kg)和联苯双酯组(0.1 g/kg),每组10只。除正常对照组外,各组均采用尾静脉注射ConA 15 mg/kg制备急性免疫性肝损伤模型,正常对照组注射等量生理盐水。建模后2 h,正常对照组和模型组以0.02 m L/g生理盐水灌胃,阳性对照组给予联苯双酯0.1 g/kg灌胃,TGCO高、中、低剂量组分别给予TGCO溶液920、460、230 mg/kg灌胃,每6 h灌胃1次,连续给药5次。末次灌药2 h后,称质量后处死小鼠,比较各组小鼠的肝脏、脾脏系数,测定小鼠血清丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)及肝匀浆中肿瘤坏死因子-α(TNF-α)、鸟氨酸氨基甲酰转移酶(OCT)、γ干扰素(IFN-γ)、白介素-1(IL-1)、白介素-6(IL-6)及超氧化物歧化酶(SOD)含量,苏木精伊红(HE)染色观察肝脏病理学变化。[结果]TGCO各剂量组和联苯双酯均能降低免疫性肝损伤小鼠增加的肝脏指数、脾脏指数(P<0.05),改善肝组织病理学变化和肝脏组织病理学分级,减轻ConA所致肝损伤的炎性反应,抑制血清ALT、AST的升高,降低肝匀浆中TNF-α、OCT、IFN-r、IL-1和IL-6含量及提高SOD的活性。[结论]TGCO对免疫性肝损伤具有一定治疗作用,并且在实验剂量范围内呈显著的剂量依赖性,其保肝机制可能与减少炎性因子的生成、抗氧化、清除自由基能力的提升以及免疫调节有关。

[Objective] To study the protective effect of total glycosides from Cornus Officinalis （TGCO） on immunological liver injury induced by concanavalin A（ConA） in mice . [Methods] The 60 C57BL mice were randomly divided into 6 groups：the normal group, the model group, positive control biphenyl group, TGCO high does group, TGCO middle dose group and TGCO low dose group （920, 460, 230 mg/kg）, with 10 mice in each group. Except normal mice, all the other mice were injected ConA 15 mL/kg once intraperitoneally and the mice in the normal groups received an equal volume of saline. The 2 h later after the annimalmodel was created, normal group and model group were given normal saline （0.02 mL/g） by gavage, positive control group was given bifendate （100 mg/kg） by gavage. TGCO high does group, TGCO middle dose group and TGCO low dose group were given TGCO at the dosage of 920, 460 and 230 mg/kg respectively, once every six hours for five times. Two hours after final administration, the mice were sacrificed and weighted to compared liver index and spleen index and detect content of serum ALT and AST,TNF-α, IFN-γ, SOD, OCT, IL-1 and IL-6 in liver homogenate. Liver pathological changes were observed by HE staining. [Results] Both of TGCO and biphenyl remarkably decreased the increased live index and spleen index （P〈0.05）, improve the histopathological changes in liver and pathological grades of liver tissues and relieve the inflam-matory reaction induced by ConA. TGCO effectively decreased the activities of ALT and AST in serum and the decreased contents of TNF-α,IFN-γ, IL-1, IL-6 and OCT in hepatic tissues, and increased levels of SOD in liver homogenate （P〈0.05）. [Conclusion] TGCO can obviously protect immunological injury liver a dose-dependent manner in the range of test doses, the mechanism possibly due to its function of anti-inflammatory, anti-oxidation, scavenging oxygen free radical and regulating immunity.