荔枝核总黄酮对肝纤维化大鼠肝组织TLR4/NF-κB信号通路的影响  

Effect of Total Flavone from Litchi chinensis Sonn on the Expression of TLR4 and NF-κB in Livers of Rats with Hepatic Fibrosis

作　　者：何志国[1] 赵永忠[1] 卢青[1] 周英琼[2] 肖绪华[1] 侯巧燕[2] 黄大健[1] 成秋宸[1] 

机构地区：[1]桂林医学院附属医院消化内科,桂林541004 [2]桂林医学院附属医院病理科,桂林541004

出　　处：《医药导报》2014年第3期286-290,共5页Herald of Medicine

基　　金：广西壮族自治区自然科学基金项目(2012GXNSFAA053105);广西壮族自治区教育厅科研资助项目(201012MS172);国家自然科学基金资助项目(81360659)

摘　　要：目的探讨荔枝核总黄酮(TFL)对胆管阻塞型肝纤维化大鼠肝组织Toll样受体4(TLR4)、核因子κB(NF-κB)表达的影响。方法雄性SPF级SD大鼠80只,随机分为正常对照组、模型组、TFL小剂量组、TFL大剂量组。除正常对照组外,其余各组均采用胆总管结扎法(CBDL)制备肝纤维化大鼠模型。造模后第2天开始,正常对照组、模型组给予0.9%氯化钠溶液灌胃(5 mL·kg-1),TFL小剂量组给予TFL 100 mg·kg-1、TFL大剂量组给予TFL 200 mg·kg-1灌胃,均每天1次,共4周,第4周末处死大鼠,留取肝脏组织。苏木精-伊红(HE)染色、Masson染色观察大鼠肝组织病理学改变,免疫组化法(IHC)检测TLR4、NF-κB在4组大鼠肝组织内的表达。结果与模型组比较,TFL大剂量组肝组织纤维化程度明显减轻,胶原表达明显减少(P<0.01);正常对照组、模型组、TFL小剂量组、TFL大剂量组的大鼠肝组织TLR4免疫组化评分分别为(0.4±0.5),(3.3±0.6),(3.1±0.5),(1.4±0.5)分;NF-κB免疫组化评分分别为(0.80±0.77),(5.12±0.89),(4.68±0.70),(3.47±0.61)分,模型组TLR4、NF-κB表达明显高于正常对照组和TFL大剂量组(P<0.01),与TFL小剂量组比较,差异无统计学意义。结论 TLR4和NF-κB高表达可能与胆管阻塞型大鼠肝纤维化的发生发展有关,大剂量荔枝核总黄酮可能通过抑制大鼠肝组织TLR4、NK-κB的表达来改善胆管阻塞型大鼠肝纤维化程度。Objective To investigate the effects of total flavone of Litchi chinensis Sonn （ TFL） on TLR4 and NF-κB expression in the livers of rats with hepatic fibrosis. Methods Eighty male SD rats were randomly divided into four groups：normal control, model control, TFL at low-dose （100 mg·kg-1 ·d-1 ）and high-dose （200 mg·kg-1 ·d-1 ）. The model of liverfibrosis in rats was induced by ligating common bile duct（CBDL） for all rats except for the normal controls. The rats were treatedwith TFL and 0. 9% physiological saline in the tested, the normal and model groups, respectively once a day for 4 weeks. All ratswere sacrificed in the end, and the livers were collected for histopathological studied by hematoxylin-eosin （H＆E） staining and Masson Trichrome （MT） examination. The expressions of TLR4 and NF-κB in livers of above four groups were detected by im-mune-histologic chemistry（IHC）. Results Compared with the model group, significantly milder liver fibrosis and lower colla-gen expression were found in the high-dose of TFL treated group（P〈0. 01）. The score of TLR4 expression in the normal and mod-el groups, TFL at low-dose and high-dose was （0. 4±0. 5）, （3. 3±0. 6）, （3. 1±0. 5）, （1. 4±0. 5）, and that of NF-κB was （0. 80±0. 77）, （5. 12±0. 89）, （4. 68±0. 70）, and （3. 47±0. 61）, respectively. The protein expression of TLR4 and NF-κB inthe model group was significantly higher than that in the normal control and TFL high-dose group（P〈0. 01）, but had no obviousdifference from the lower dose group. Conclusion Higher expression of TLR4 and NF-κB may be involved in the liver fibroge-nisis and development by CBDL in rats. TFL at high-dose may improve liver fibrosis induced by CBDL via inhibiting the expres-sion of TLR4 and NF-κB in hepatic tissue in rats.

关 键 词：荔枝核总黄酮 肝纤维化 TOLL样受体4 核因子-ΚB 

分 类 号：R286[医药卫生—中药学] R965[医药卫生—中医学]