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Abstract：
OBJECTIVE: To investigate the influence of cyclosporin A (CsA) pre-treatment and etomidate (ETO) post-treatment on lung injury induced by limb ischemia-reperfusion (I/R) in rats.
METHODS: Rats were randomly divided into five groups: sham, I/R, I/R+CsA, I/R+ETO, and I/R+CsA+ETO. Limb I/R lung injury was established by bilateral clamping of the femoral arteries for 2 hours. Following reperfusion for 3 hours, blood gas analysis was performed. Pathological changes were assessed using immunohistochemistry. The apoptosis index (AI) and wet/dry weight ratio (W/D) were calculated. Levels of Fas protein and FasL mRNA were assessed by western blotting and RT-PCR, respectively. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were detected by ELISA.
RESULTS: I/R resulted in decreased PaO2 but increased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1β. Scattered punctate apoptosis and necrosis were observed by immunohistochemistry. Compared with the I/R group, the I/R+ETO and I/R+CsA groups showed increased SpO2, decreased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1β, and decreased numbers of apoptotic and necrotic cells. Combined treatment with CsA+ETO resulted in more dramatic changes in these parameters.
CONCLUSIONS: ETO post-treatment and CsA pretreatment reduced lung injury induced by limb I/R in rats. The mechanism may be related to synergistic inhibition of Fas/FasL signaling.
METHODS: Rats were randomly divided into five groups: sham, I/R, I/R+CsA, I/R+ETO, and I/R+CsA+ETO. Limb I/R lung injury was established by bilateral clamping of the femoral arteries for 2 hours. Following reperfusion for 3 hours, blood gas analysis was performed. Pathological changes were assessed using immunohistochemistry. The apoptosis index (AI) and wet/dry weight ratio (W/D) were calculated. Levels of Fas protein and FasL mRNA were assessed by western blotting and RT-PCR, respectively. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were detected by ELISA.
RESULTS: I/R resulted in decreased PaO2 but increased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1β. Scattered punctate apoptosis and necrosis were observed by immunohistochemistry. Compared with the I/R group, the I/R+ETO and I/R+CsA groups showed increased SpO2, decreased AI, W/D, Fas, FasL mRNA, TNF-α and IL-1β, and decreased numbers of apoptotic and necrotic cells. Combined treatment with CsA+ETO resulted in more dramatic changes in these parameters.
CONCLUSIONS: ETO post-treatment and CsA pretreatment reduced lung injury induced by limb I/R in rats. The mechanism may be related to synergistic inhibition of Fas/FasL signaling.
摘要：
目的：探讨环孢素A(CsA)预处理和依托咪酯(ETO)后处理对大鼠肢体缺血再灌注(I/R)肺损伤的影响。
方法:大鼠随机分为5组,I/R,I/R+CsA,I/R+ETO,和I/R+CsA+ETO。通过双侧夹闭股动脉2小时建立肢体I/R肺损伤。再灌注3小时后，进行血气分析.使用免疫组织化学评估病理变化。计算细胞凋亡指数(AI)和湿/干重比(W/D)。通过蛋白质印迹和RT-PCR评估Fas蛋白和FasLmRNA的水平。分别。ELISA法检测肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β。
结果：I/R导致PaO2降低，但AI增加，W/D,Fas,FasLmRNA,TNF-α和IL-1β。免疫组化观察到散点状细胞凋亡和坏死。与I/R组比拟，I/R+ETO和I/R+CsA组显示SpO2升高，AI降低，W/D,Fas,FasLmRNA,TNF-α和IL-1β,凋亡和坏死细胞的数量减少。与CsA+ETO联合治疗导致这些参数发生更剧烈的变化。
结论：ETO后处理和CsA预处理减轻了大鼠肢体I/R引起的肺损伤。其机制可能与Fas/FasL信号的协同抑制有关。
方法:大鼠随机分为5组,I/R,I/R+CsA,I/R+ETO,和I/R+CsA+ETO。通过双侧夹闭股动脉2小时建立肢体I/R肺损伤。再灌注3小时后，进行血气分析.使用免疫组织化学评估病理变化。计算细胞凋亡指数(AI)和湿/干重比(W/D)。通过蛋白质印迹和RT-PCR评估Fas蛋白和FasLmRNA的水平。分别。ELISA法检测肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β。
结果：I/R导致PaO2降低，但AI增加，W/D,Fas,FasLmRNA,TNF-α和IL-1β。免疫组化观察到散点状细胞凋亡和坏死。与I/R组比拟，I/R+ETO和I/R+CsA组显示SpO2升高，AI降低，W/D,Fas,FasLmRNA,TNF-α和IL-1β,凋亡和坏死细胞的数量减少。与CsA+ETO联合治疗导致这些参数发生更剧烈的变化。
结论：ETO后处理和CsA预处理减轻了大鼠肢体I/R引起的肺损伤。其机制可能与Fas/FasL信号的协同抑制有关。
