NF-κB和HMGB1在大鼠肠缺血再灌注肺损伤中的表达及白藜芦醇苷的保护作用

Expressions of HMGB1mRNA and NF-κB in lung injury induced by intestinal ischemia-reperfusion in rats and protective effects of polydatin

目的:探讨肠缺血再灌注(Intestinal ischemia-reperfusion,IIR)肺损伤核转录因子-κB(Nuclearfactor-kappaB,NF-κB)的活性和高迁移率族蛋白1(High mobility group box1,HMGB1)基因表达及白藜芦醇苷(Polydatin,PD)的保护作用。方法:54只Sprague-Dawley(SD)大鼠随机分成对照组、肠缺血45min继以再灌注组(再灌注0.5h、2h、6h)及肠缺血45min继以再灌注同时给予PD治疗组(再灌注0.5h、2h、6h)。采用比色法检测肺组织髓过氧化物酶(myeloperoxidase,MPO)水平、免疫组化法检测细胞间黏附分子-1(Intercellular adhesion molecule-1,ICAM-1)和NF-κB的表达、RT-PCR检测肺组织高迁移率族蛋白1(HMGB1)mRNA。结果:IIR后肺组织明显水肿、出血和炎性细胞侵润。与对照组相比,肺组织W/D、MPO水平明显升高,ICAM-1及NF-κB的蛋白表达,HMGB1mRNA(2h、6h)的表达增强(P<0.05);白藜芦醇苷干预后肺损伤程度减轻、各项指标明显改善(P<0.05)。结论:PD可以减轻肠缺血再灌注肺损伤,作用机制可能与其抑制NF-κB活化,降低肺组织HMGB1mRNA的表达上调密切相关。

Objective： To evaluate the activity of nuclear factor kappaB （ NF- κB ） and the gene expression of high mobility group box 1 （HMGB 1 ） in lung injury induced by intestinal ischemia-reperfusion （IIR）, and to investigate the protective effect of polydatin（ PD ） in this lung injury. Methods： Fifty-four male Sprague-Dawley rats weighing 200-250 g were randomly divided into control group, IIR group （ 45 min intestinal ischemia with 0.5 h or 2 h or 6 h reperfusion） and PD group [IIR with PD （ 10 mg/kg） treatment].The level of pulmonary myeloperoxidase （MPO） was detected by colorimetric method,the expressions of NF- κB and ICAM-1 by immuneochemistry and that of pulmonary HMGBlmRNA by RT-PCR respectively. Results： Lung injury induced by IIR was characterized by pathological damage of edema, hemorrhage and inflammatory cell infiltration. Compared with control group, pulmonary W/D and MPO increased significantly（P〈 0.05 ）.Positive expressions of NF-κB p65 and ICAM-1 protein , and HMGB 1 mRNA （2 h,6 h） also increased significantly（P〈0.05 ）. After administration of PD, the levels of pulmonary indices were improved significantly（P〈0.05 ）, pulmonary damage alleviated compared with IIR group（P〈0.05 ）, and the expresion of NF- κB became weak. Conclusion： Injection of polydatin before reperfusion could alleviated lung injury induced by intestinal ischemia-reperfusion in rats in vivo, which is possibly through inhibiting pulmonary NF-κB activation and attenuating the expression of HMGB 1 mRNA during lung injury in rats.