Variation of Fas/Fasl pathway in limb ischemia-reperfusion lung injury rats after etomidate post-treatment

doi:10.3969/j.issn.2095-4344.2865

Abstract

Abstract:

BACKGROUND: To date, it has been confirmed that etomidate pre-treatment can reduce the damage of remote organs caused by limb ischemia-reperfusion, but whether etomidate post-treatment has protective effect on remote organs and its mechanism has been rarely reported.

OBJECTIVE: To investigate the influence of etomidate post-treatment on limb ischemia-reperfusion lung injury.

METHODS: A rat model of limb ischemia-reperfusion lung injury was prepared by clamping the bilateral femoral arteries for 2 hours and reperfusion for 3 hours. After 2 hours of limb ischemia, I/R group experienced the process of limb ischemia-reperfusion; I/R+ETO group, I/R+Dex 0.2 group, I/R+Dex 0.5 group and I/R+Dex 1.0 group, besides the model of limb ischemia-reperfusion, were injected with etomidate 1.0 mg/kg and dexamethasone 0.2, 0.5 and 1.0 mg/kg respectively through tail vein. At 3 hours of reperfusion, blood samples were extracted from the carotid artery, blood gas analysis was performed and the partial pressure of blood oxygen (PaO₂) was recorded. The pathological changes were detected by immunohistochemistry. Apoptotic index was detected by Hoechst 33258 staining and wet/dry weight ratio was detected. Fas protein and Fasl mRNA of lung tissue were detected by western blot and RT-PCR respectively. Tumor necrosis factor-α and interleukin-1β levels were detected by ELISA.

RESULTS AND CONCLUSION: Compared with the I/R group, PaO₂ increased (P < 0.05), Apoptotic index, wet/dry weight ratio, Fas and FasL mRNA, tumor necrosis factor-α and interleukin-1β decreased in the I/R+ETO group, and the number of apoptotic lesions decreased in the I/R+ETO group (P < 0.05). Compared with the I/R+ETO group, the change of each index was not statistically significant in the I/R+Dex 0.5 group (P > 0.05). To conclude, etomidate post-treatment can reduce lung injury caused by limb ischemia-reperfusion in rats, and its mechanism may be related to the down-regulation of Fas/FasL. In the statistical point of view, etomidate 1.0 mg/kg has the potency intensity of reducing lung injury, almost equivalent to dexamethasone 0.5 mg/kg.

Key words: etomidate, post-treatment, ischemia-reperfusion, lung, Fas, FasL, apoptotic index, PaO2, tumor necrosis factor-α, interleukin-1β, rat

CLC Number:

Zou Haibo, Sun Xiaofeng. Variation of Fas/Fasl pathway in limb ischemia-reperfusion lung injury rats after etomidate post-treatment[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(32): 5162-5167.

Figures/Tables 8

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