Effects Of Stimulating κ Opioid Receptors On Alleviating High Altitude Pulmonary Edema And Some Relative Mechanisms Research

HAPE (High altitude pulmonary edema)， with acute phase in onset and process，is a severe acute high altitude disease accompanied serious outcomes. It is in greatdilemma for current therapy as for it did not show much benefit in prevention andcurative effects. Recent studies proved effects of prevention for apioid receptorstimulator in pulmonary ischemia reperfusion injury and hypotension and hypoxiainduced pulmonary hypertension. This study was proposed to evaluate effects of kappaopioid receptor stilulator on haemodynamic and histological changes， oxidativemetabolism and oxidation stress in rodent HAPE model，and find correlative risk factors.At last， evaluate clinical application probability and efficiency of kappa opioid receptorstimulator， and analysis biological molecular mechanisms with aim at seeking new wayof HAPE inhibition.Objective： To observe effects of protection for kappa opioid receptor stimulator on highaltitude pulmonary edema rats which established in pressure and oxygen lacking cabinequaling to high altitude surroundings. Secondarily, analysis correlative mechanismswith aim of proceeding study upon etiology and inhibition strategy of high altitudepulmonary edema.Methods：Four groups included40randomly stratified Sprague-Dawley rats.(eight pergroup)， including normoxia control group，2d hypobaric hypoxia group， normalsaline+2d hypobaric hypoxia， U50，488H+2d hypobaric hypoxia and nor-BNI+U50，488H+2d hypobaric hypoxia. Rat HAPE models were established by hypobaric hypoxictreating system.2d hypobaric hypoxia group received no treatment before into thehyperbaric chamber; normal saline+2d hypobaric hypoxia group intraperitoneal wereinjected of saline1.25ml/kg3days before into the hyperbaric chamber，U50，488H+2dhypobaric hypoxia group intraperitoneal were injected of U50，488H1.25mg.kg-1.d-13days before into the hyperbaric chamber， nor-BNI+U50，488H+2d hypobaric hypoxiagroup intraperitoneal were injected of nor-BNI2.0mg.kg-1.d-1， then10min laterintraperitoneal injected U50，488H1.25mg.kg-1.d-13days before into the hyperbaricchamber. All parameters measured contained hemodynamic oscillation， lung watercontent， lung morphology， lung tissue nitric oxide (NO)， inducible nitric oxidesynthase (iNOS)， malondialdehyde (MDA)， superoxide dismutase (SOD)， endothelin-1(ET-1)， thromboxane B2(TXB2)，6-keto-prostaglandin F1(6-keto-PGF1) andserum concentrations of malondialdehyde (MDA)， superoxide dismutase (SOD) anderythropoietin (EPO).Results：Compared to group C, all values including mPAP, pulmonary water content, innerpulmonary ET-1, MDA, TXB2,6-keto-PGF1,TXB2/6-keto-PGF1, iNOS, serum MDAand EPO were higher in the last four goups, but pulmonary NO and SOD decreased,P<0.05. Compared to group H, all values including mPAP, pulmonary water content, inner pulmonary ET-1, MDA, TXB2,6-keto-PGF1,TXB2/6-keto-PGF1, iNOS, serumMDA and EPO decreased in goup UH, but pulmonary NO and SOD increased, P<0.05.All prior values performed no difference between group NH and group NUH, P>0.05.Conclusion：Stimulative κ opioid receptor had positive effects in inhibition high altitudepulmonary edema, mechanisms may result from its inhibiting lipoid superoxide reactionand correct unbalance of systolic/diastolic vessel factors.