虎杖甙下调兔肺缺血再灌注损伤时TLR4的表达  

Polydatin downregulates TLR4 expression in lung ischemia reperfusion injury in rabbits

作　　者：金晓凤[1] 徐正衸[1] 王万铁[1] 许益笑[1] 

机构地区：[1]温州医学院病理生理学教研室,浙江温州325025

出　　处：《中国病理生理杂志》2008年第4期666-669,共4页Chinese Journal of Pathophysiology

基　　金：浙江省卫生厅科研基金资助项目(NoSWS00021)

摘　　要：目的:研究家兔肺缺血再灌注损伤时Toll样受体4(TLR4)信号转导通路变化及虎杖甙(PD)对其影响。方法:复制在体肺缺血再灌注损伤模型。健康日本大耳白免30只,随机分为对照(C)组、缺血再灌注(IR)组、PD组。鲎试剂试管法检测血浆内毒素(ET);免疫组化法检测肺组织TLR4、核因子-κB p65(NF-κB p65)和热休克蛋白70(HSP70)的蛋白表达;原位杂交法检测肺组织细胞间黏附分子-1(ICAM-1)mRNA表达;电镜观察肺超微结构变化。结果:IR组、PD组与C组相比血浆ET无显著差异(均P>0.05)。IR组肺组织TLR4、NF-κB p65、HSP70蛋白及ICAM-1 mRNA表达较C组显著升高(均P<0.01);PD组上述改变较IR组明显下降,但仍高于C组(均P<0.01);电镜见PD组肺超微结构损伤明显轻于IR组。结论:肺缺血再灌注损伤过程中HSP70合成增加,作为内源性配体之一上调TLR4,可能通过激活NF-κB,进而诱导ICAM-1的转录和分泌。PD可以下调该信号转导途径,减轻肺缺血再灌注损伤。AIM ： To explore the influence of polydatin （PD） on Toll - like receptor 4 （TLR4） signal transduction pathway during lung ischemia reperfusion injury in rabbits. METHODS： Rabbit lung model of ischemia reperfusion （IR） injury was constituted in vivo. Thirty rabbits were divided into groups randomly： control （C）, IR and PD group, respectively. The concentration of endotoxin （ET） in plasma was analyzed by end -point chromogenic assay. The protein expressions of TLR4, nuclear factor （NF） - κB p65 and heat shock protein 70 （HSP70） were measured by immunohistochemistry. The intracellular adhesion molecule - 1 （ ICAM - 1 ） mRNA expression was detected by in situ hybridization histochemistry. The ultrastructural changes were observed by electron microscope. RESULTS ： No significant difference of ET concentration in plasma between groups （all P 〉0. 05） was observed. The protein expressions of TLR-4, NF-κB p65, HSP70 and ICAM - 1 mRNA in IR group were significantly increased as compared to C group and PD group, while those expressions in PD group were evidently higher than those in C group （ all P 〈 0. 01 ）. The lung pathological injuries in PD group were obviously alleviated as compared to IR group under electron microscope. CONCLUSION： It suggests that lung ischemia reperfusion releases endogenous ligands of TLR4 as HSPT0, then activates NF - κB, promotes the release of mediators of inflammation such as ICAM - 1. PD might have a protective effect on lung ischemia repeffusion injury by regulating TLR4 signal transduction pathway.

关 键 词：虎杖甙 肺 再灌注损伤 受体 Toll样 NF-κB P65 热休克蛋白质70 

分 类 号：R363[医药卫生—病理学]