目的:探讨前列环素(PGI2)和血栓素A2(TXA2)在机械通气(MV)所致兔肺通透性增高中的作用。
目的:将48只健康日本大白兔随机分为载体治疗组(V组),tranylcypromine(PGI2合酶抑制剂)治疗组(T组),达唑昔本(TXA2合成酶抑制剂)治疗组(D组),车辆处理的MV组(VM组),转酰甘油化的MV组(TM组)和达唑昔本治疗的MV组(DM组)。ELISA法测定肺组织中PGI2和TXA2的含量以及BALF和肺组织中TNF-α的水平。肺湿/干重(W/D)比,检测肺通透性指数及肺组织肌球蛋白轻链激酶(MLCK)蛋白和mRNA的表达,评价肺通透性。通过肺组织学评分评估肺损伤的严重程度。
目的:在接受无MV的不同处理的兔子中,测得的参数没有显着差异。在VM组中的兔子中,肺中PGI2和TXA2的含量,BALF和肺组织中的TNF-α,PGI2/TXA2比值,肺W/D比,肺通透性指数,与V组相比,肺MLCK蛋白和mRNA的表达以及肺组织学评分均显着增加(P<0.05)。T组和D组。在接受MV的兔子中,环丙胺抑制PGI2的产生显著降低了PGI2/TXA2比值(P<0.05),进一步增强了BALF和肺组织中TNF-α的产生(P<0.05),肺通透性增高和肺损伤加重(P<0.05),而达唑昔本治疗可显著降低肺组织中TXA2的产生(P<0.05),PGI2/TXA2比值增加(P<0.05),BALF和肺组织中TNF-α的产生减少(P<0.05),从而减轻肺的高通透性和肺损伤(P<0.05)。
目的:PGI2通过下调TNF-α/MLCK信号通路对MV诱导的肺高通透性和肺损伤具有保护作用,TXA2可通过上调TNF-α/MLCK信号通路加重MV诱导的兔肺通透性增高。
OBJECTIVE: To explore the role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in lung hyper-permeability induced by mechanical ventilation (MV) in rabbits.
OBJECTIVE: Forty-eight healthy Japanese white rabbits were randomly allocated to vehicle treatment group (group V),
tranylcypromine (a PGI2 synthase inhibitor) treatment group (group T), dazoxiben (a TXA2 synthase inhibitor) treatment group (group D), vehicle-treated MV group (group VM), tranylcyprominetreated MV group (group TM) and dazoxiben-treated MV group (group DM). The contents of PGI2 and TXA2 in the lung tissues and TNF-α level in BALF and lung tissues were measured by ELISA. The lung wet/dry weight (W/D) ratio, lung permeability index and pulmonary expressions of myosin light chain kinase (MLCK) protein and mRNA were detected to evaluate the pulmonary permeability. The severities of lung injury were assessed by lung histological scores.
OBJECTIVE: The measured parameters did not differ significantly among the rabbits receiving different treatments without MV. In rabbits in group VM, the contents of PGI2 and TXA2 in the lungs, TNF-α in BALF and lung tissues, PGI2/TXA2 ratio, lung W/D ratio, lung permeability index, pulmonary expressions of MLCK protein and mRNA and histological scores of the lungs all increased significantly (P < 0.05) as compared with those in group V, group T and group D. In rabbits undergoing MV, inhibition of PGI2 production by
tranylcypromine significantly decreased the PGI2/TXA2 ratio (P < 0.05), further enhanced the production of TNF-α in the BALF and lung tissue (P < 0.05), and worsened lung hyper-permeability and lung injury (P < 0.05), while treatment with dazoxiben significantly reduced TXA2 production in the lung tissue (P < 0.05), increased the PGI2/TXA2 ratio (P < 0.05) and decreased TNF-α production in the BALF and lung tissue (P < 0.05), thus resulting in alleviated lung hyperpermeability and lung injury (P < 0.05).
OBJECTIVE: PGI2 plays a protective role against MV-induced lung hyper-permeability and lung injury by downregulating TNF-α/MLCK signaling pathway, while TXA2 can exacerbate MV-induced lung hyperpermeability in rabbits by up-regulating TNF-α/ MLCK signaling pathway.