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目的观察TNF-α拮抗剂可溶性TNFRI-Fc融合蛋白对抗大鼠肺缺血再灌注损伤的作用,并探讨其可能机制。方法选择体质量250～350 g的雄性SD大鼠72只,随机分为3组,每组24只,假手术组(C组)仅开胸,不行肺缺血及再灌注处理;Ⅰ组与Ⅱ组开胸行左肺缺血和再灌注处理,Ⅱ组在肺门阻断前及肺门开放前5 min经颈静脉留置针推注溶于生理盐水中的可溶性TNFRI-Fc融合蛋白(3μg/kg)。分别于再灌注后或开胸后1、3、6、12 h颈动脉放血处死大鼠,取左肺上1/3制成匀浆用于检测TNF-α、IL-8、MDA、SOD,中1/3测肺组织湿/干重比(W/D),下1/3用于光镜下肺组织病理学观察。结果 C组各时间点肺组织匀浆内TNF-α、IL-8、MDA含量、SOD活力无明显变化,肺组织在光镜下无明显变化,Ⅰ组TNF-α、IL-8、MDA含量在1、3、6、12 h时间点较C组明显升高,而SOD活力明显降低,肺内有严重的毛细血管充血及炎性细胞浸润;Ⅱ组各时间点肺组织匀浆内TNF-α、IL-8、MDA含量、W/D较Ⅰ组明显降低,SOD活力升高,且TNF-α达峰时间明显错后,病理形态学检查示炎性细胞浸润明显减轻。结论可溶性TNFRI-Fc融合蛋白可对抗肺缺血再灌注损伤,其效果与其有效中和TNF-α并阻断其生物学活性有关。
Objective To investigate the effect of TNF-α antagonist soluble TNFRI-Fc fusion protein on lung ischemia-reperfusion injury in rats and its possible mechanism. Methods Seventy-two male Sprague-Dawley rats weighing 250-350 g were randomly divided into three groups (24 rats in each group). The sham operation group (C group) only had thoracotomy without pulmonary ischemia and reperfusion. Group Ⅱ was subjected to left lung ischemia and reperfusion. The rats in group Ⅱ were injected with soluble TNFRI-Fc fusion protein (3 μg) dissolved in saline before the hilar block and 5 minutes before the hilar opening / kg). Rats were sacrificed by carotid artery after reperfusion or at 1, 3, 6, and 12 h after thoracotomy, respectively, and 1/3 of the left lung was made into a homogenate for detection of TNF-α, IL-8, MDA, One third of the lung tissue wet / dry weight ratio (W / D), the next one third for lung tissue pathology under light microscopy. Results The contents of TNF-α, IL-8 and MDA and the activities of SOD in lung homogenate of group C were not significantly changed at each time point. There were no significant changes in lung tissue under light microscope. The levels of TNF-α, IL-8 and MDA At 1, 3, 6, 12 h time points than C group was significantly increased, while SOD activity was significantly reduced lungs with severe capillary congestion and inflammatory cell infiltration; group Ⅱ at each time point lung tissue homogenate TNF- α, IL-8, MDA content, W / D were significantly lower than those in group Ⅰ, SOD activity was elevated, TNF-α peak time was significantly wrong, pathological examination showed significantly reduced inflammatory cell infiltration. Conclusions Soluble TNFRI-Fc fusion protein can protect against lung ischemia-reperfusion injury and its effect is related to its ability to neutralize TNF-α and block its biological activity.