乌司他丁对机械通气相关性肺损伤模型兔肺组织中TNF-α的影响

摘要

目的：建立机械通气相关性肺损伤模型兔肺组织，观察TNF-α在机械通气相关性肺损伤模型兔肺组织中TNF-α的变化规律，探讨乌司他丁对呼吸机所致肺损伤（ventilator-induced lung injury， VILI）的治疗机制是否与抑制TNF-α的活化有关。方法：采用大潮气量通气建立呼吸机相关肺损伤兔模型，模型成立后30、60、120、180、240 min，抽取动脉血作血气分析，采用ELISA法检测血清肺组织中TNF-α的含量，采用HE染色观察肺组织病理变化，运用Real-time PCR、Western Blot检测肺组织中TNF-αRNA、蛋白的表达。结果：家兔在大潮气量机械通气后，随着时间的增加血清中、肺组织中TNF-α表达显著增加，而采呼吸机相关性肺损伤模型兔在使用乌司他丁干预后，动脉血中的PaO2较前有所回升，血清与肺组织中TNF-αmRNA与蛋白的表达同大潮气量组相比有明显著上升（P<0.05）。结论：乌司他丁对呼吸机相关性肺损伤有保护作用，其机制可能是通过下调TNF-α的表达，抑制炎症反应来实现的。%Objective:The establishment of ventilator induced lung injury in a rabbit model of lung tissue, to observe the changes of TNF-α in mechanical ventilation induced lung injury model of rabbit lung tissue alpha, to explore the therapeutic mechanism of Ulinastatin on VILI and TNF-α.Method:The injury rabbit model of high tidal volume ventilation was established,after 30,60,120,180 and 240 min,arterial blood for blood gas analysis.TNF-α in serumwere measured by ELISA.The pathological changes of lung tissue were observed by HE staining.The expression of TNF-αRNA and protein in lung tissue was detected by PCR Real-time and Blot Western.Result:After mechanical ventilation,the expression of TNF-α in serum and lung tissue increased significantly.Ulinastatin interved ventilator induced lung injury model in rabbits and rabbit arterial blood PaO2 increased,in serum and lung tissue TNF-α expression were compared with those of the earlier high tidal volume group improved significantly(P<0.05).Conclusion:Ulinastatin on ventilator induced lung injury has a protective effect, he mechanism may be by down regulating the expression of TNF-α,inhibit inflammatory reaction to achieve.