机械通气论文：氯沙坦对机械通气大鼠肺组织TNF-α和MPO表达的影响.docVIP

机械通气论文：氯沙坦对机械通气大鼠肺组织TNF-α和MPO表达的影响 【中文摘要】呼吸机所致肺损伤（ventilator induced lung injury，VILI）是机械通气最严重的并发症，研究其发病机理和防治措施对提高机械通气应用水平有重要价值。近年来研究发现，肾素-血管紧张素系统（Renin-angiotensin system, RAS）不但在急性肺损伤（ALI）时炎症反应、氧化应激和细胞凋亡中发挥了重要作用，而且在VILI发病中也具有重要作用。因此，适当应用血管紧张素Ⅱ（AngⅡ）受体拮抗剂或血管紧张素转化酶抑制剂对VILI应具有一定防治作用。通过观察AngⅡ受体拮抗剂氯沙坦对机械通气大鼠肺组织TNF-α水平和MPO活性的影响，探讨氯沙坦对呼吸机所致肺损伤的保护作用。方法24只健康雄性Wister大鼠随机分为对照组、呼吸机致肺损伤组（VILI）和氯沙坦干预组（LAP），分别采用ELISA法测定大鼠肺组织中AngⅡ含量，免疫组织化学染色法测定大鼠肺组织TNF-α蛋白表达水平，化学比色法测定肺组织匀浆中MPO活性。结果1．病理学改变：除对照组外，VILI组与LAP组肺组织均有不同程度的损伤，表现为肺间质充血水肿、炎细胞浸润，肺泡间隔增厚、肺泡破裂融合，但LAP较VILI组明显减轻；2．VILI组大鼠肺W/D比值较对照组和LAP组高（P＜0.01）；对照组与LAP组差异尚无统计学意义（P＞0.05）；3．VILI组和LAP组大鼠肺组织匀浆中AngⅡ含量较对照组高（P＜0.01），LAP组与VILI组比较差异尚无统计学意义（P＞0.05）；4．VILI组大鼠肺组织TNF-α蛋白表达水平较对照组和LAP组高（P＜0.01）；对照组与LAP组比较差异尚无统计学意义；5．VILI组大鼠肺组织匀浆中MPO活性较对照组和LAP组高（P＜0.01）；对照组与LAP组比较差异尚无统计学意义（P＞0.05）；6.对照组及VILI组大鼠肺组织TNF-α蛋白表达与肺组织AngⅡ含量之间呈正相关。结论1．VILI时肺组织AngⅡ含量与TNF-α蛋白表达量之间呈正相关，AngⅡ可能通过调控肺组织中TNF-α的表达在VILI发病中起重要作用。2．氯沙坦可阻断AngⅡ与AT1受体的结合，进而抑制TNF-α的表达，对VILI具有一定防治作用。 【英文摘要】Background Ventilator-induced lung injury（VILI）is the most serious complication ofmechanical ventilation, study the pathogenesis and prevention measures to improve the level ofapplication of mechanical ventilation has significant values. Recent studies found that therenin-angiotensin system (RAS) is not only played an important role in the inflammatoryresponse , oxidative stress and apoptosis of acute lung injury (ALI), but also played an importantrole in the VILI. Therefore, application of angiotensinⅡ(AngⅡ) receptor antagonist orangiotensin converting enzyme inhibitors appropriately should have a preventive effect on VILI. To explore the effect of the AT1 inhibitor Losartan on the expression of TNF-αinthe mechanical ventilation rat lung and MPO, Further study , the protection of Losartan forventilator induced lung injury.Methods Twenty-Four healthy male Wister rats were randomly divided into three groups:control group, VILI group and Losartan group. Immunohistochemical staining and ELISA in situwere