Effects Of Cyclosporine A On Protecting Lung With Ischemia/Reperfusion In Rabbits

Background: Cardiopulmonary bypass is an important auxiliary measure in the processof cardiac surgery. With the development of technology, measures on myocardialprotection have improved and achieved satisfactory results, but the incidence ofpulmonary complications is still higher than cardiac complications, especially incritically ill patients and infants. So the lung dysfunction is becoming the primarycomplication and the main reason for people to die after the process of cardiopulmonarybypass. the lung dysfunction after cardiopulmonary bypass is mainly caused byischemia-reperfusion injury, and cell apoptosis is the primary mechanism in thisprocedure. With the deeper research on ischemia-reperfusion injury, researchers havefound that mitochondrial permeability transition pore is an important structure in themitochondrial membrane and participates in the process of cell apoptosis. CyclosporineA is a superactive immunosuppressive agents, it can inhabit the opening ofmitochondrial permeability transition pore in the process of reperfusion and play cellprotection.Objective: To establish single lung in vivo ischemia/reperfusion rabbit model, injectcyclosporine A through pulmonary artery, then observe change of lung morphousthrough electron microscope, detect the content of cytochrome C in lung cells throughimmunohistochemisty and detect cell apoptosis in lung by method of terminaldeoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL). according allthese results, we can evaluate the protection of cyclosporine A on lungischemia-reperfusion injury and provide theoretical basis about lung protection in theprocess of cardiopulmonary bypass. Method: Single lung in vivo ischemia/reperfusion animal model was used.40rabbitswere randomly averagely divided into four groups: sham(S) group, cyclosporineA(CsA) group, low molecular dextran(LMD) and ischemia/reperfusion (I/R) group.Pentobarbital sodium(30mg/Kg) was injected through ear veins in order to anesthetizerabbits, then fixed rabbits on the operating table and connected the rabbits to respirator.To open the chest of rabbits through the center of it, ionizate the left hilum of lung anddetain block-tie. Injecting heparin(2ml/Kg) into the rabbits, blocking the left hilum oflung and decreasing1/3tidal volume.45minutes later, inject drugs through leftpulmonary artery, and then open the left hilum of lung.3hours later, killing the rabbitsand slicing the same domain of left lung in order to do further research. Apoptosis oflung tissue pneumocyte was assessed by TUNEL method, Cytochrome C(CytC) in lungtissue was detected by immunohistochemistry techniques, the damage of mitochondrialwas observed through the electron microscope.Results: Observing the cell mitochondria by electronic microscope, the worstdestructiveness of mitochondria is I/R group, then LMD group, CsA group and S group.The content of CytC in cytoplasm and the value of apoptosis index (AI)in B group wereevidently higher than that in S group, but it’s evidently lower than that in LMD groupand I/R group, and the value of apoptosis index (AI) and CytC in cytoplasm in LMDgroup.Conclusion: CsA can inhibit the opening of mPTP in early reperfusion, block theapoptosis of lung tissue pneumocyte, and protect the lung against ischemia/reperfusion.