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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

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【作者】 何志国赵永忠卢青周英琼肖绪华侯巧燕黄大健成秋宸

【Author】 HE Zhi-guo;ZHAO Yong-zhong;LU Qing;ZHOU Ying-qiong;XIAO Xu-hua;HOU Qiao-yan;HUANG Da-jian;CHENG Qiu-chen;Department of Gastroenterology,the Affiliated Hospital of Guilin Medical College;Department of Pathology,the Affiliated Hospital of Guilin Medical College;

【机构】 桂林医学院附属医院消化内科桂林医学院附属医院病理科

【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。

【Abstract】 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 liver fibrosis in rats was induced by ligating common bile duct( CBDL) for all rats except for the normal controls. The rats were treated with TFL and 0. 9% physiological saline in the tested,the normal and model groups,respectively once a day for 4 weeks. All rats were 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 immune-histologic chemistry( IHC). Results Compared with the model group,significantly milder liver fibrosis and lower collagen expression were found in the high-dose of TFL treated group( P < 0. 01). The score of TLR4 expression in the normal and model 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 in the model group was significantly higher than that in the normal control and TFL high-dose group( P < 0. 01),but had no obvious difference from the lower dose group. Conclusion Higher expression of TLR4 and NF-κB may be involved in the liver fibrogenisis and development by CBDL in rats. TFL at high-dose may improve liver fibrosis induced by CBDL via inhibiting the expression of TLR4 and NF-κB in hepatic tissue in rats.

【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)
  • 【文献出处】 医药导报 ,Herald of Medicine , 编辑部邮箱 ,2014年03期
  • 【分类号】R285.5
  • 【被引频次】25
  • 【下载频次】359
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