松弛素对大鼠肺缺血-再灌注损伤的作用

Effects of relaxin on lung ischemia-reperfusion injury in rats

目的探讨松弛素（relaxin,RLX）在大鼠生理状态下和肺缺血-再灌注损伤时的作用。方法健康雄性SPF级SD大鼠32只,体重250~300g,采用随机数字表法将大鼠随机均分为四组：假手术组（S组）,假手术＋RLX处理组（S＋R组）,肺缺血-再灌注损伤组（IR组）,肺缺血-再灌注损伤＋RLX处理组（IR＋R组）。采用缺血1h,再灌注2h的方法制备在体大鼠左肺缺血-再灌注损伤模型。S＋R组和IR＋R组于再灌注前静脉注射人型重组RLX 5μg/kg,S组和IR组在相同时刻给予等容量PBS缓冲液。于再灌注结束时采集左心室血样和肺组织,光镜下观察病理学结果,测定四组大鼠肺功能,湿干重比（W/D）,肺组织髓过氧化物酶（MPO）活性,血浆丙二醛（MDA）、内皮素-1（ET-1）的含量。结果 S组与S＋R组各项指标差异均无统计学意义。与S组比较,IR组和IR＋R组肺组织病理学损伤严重,W/D、MPO活性、血浆MDA、ET-1含量明显升高（P〈0.05）,IR组PaO2明显降低,PaCO2明显升高（P〈0.05）,IR＋R组PaO2明显降低（P〈0.05）,PaCO2差异无统计学意义;与IR组比较,IR＋R组肺组织病理学损伤明显减轻,W/D、MPO活性、PaCO2、血浆MDA、ET-1含量均明显降低（P〈0.05）,PaO2明显升高（P〈0.05）。结论松弛素减轻了肺缺血-再灌注损伤,其机制可能与降低内皮素表达保护内皮、减少白细胞聚集、防止氧自由基所致的组织损伤等有关,且未发现松弛素对生理状态下的肺组织有明显影响。

Objective To study the effects of relaxin （RLX） on lung tissues in the physiological state and lung ischemia-reperfusion injury in rats. Methods Thirty-two healthy male SPF SD rats, weighing 250-300 g, were randomly divided into four groups using random number table method （n=8 each） ： sham group （group S）, shamtRLX-treated group （group StR）, lung ischemia-reperfusion injury group （group IR） and lung ischemia reperfusion injuryt RLX-treated group （group IRtR）. The ischemia-reperfusion model was produced in group IR and group IRtR by clamping the rats＇ left pulmonary hilum for 1 h followed by 2 h reperfusion. In group StIR and group IRtR, human recombinant RLX （5μg/kg） was injected intravenously before the reperfusion while in group S and group IR, equal volume of PBS buffer solution was given at the same time. At the end of reperfusion, left ventricular blood sample and lung tissues were collected. Pathological changes of the lung tissues observed under light microscope, lung function, wet/dry lung weight ratio （W/D）, myeloperoxidase （MPO） activity, plasma malondialdehyde （MDA） and endothelin-1 （ET-1） content were compared between the four groups. Results There was no significant difference of the parameters between group S and group St R. Compared with group S, the pathological damage of lung tissues, W/D, MPO activity, plasma MDA and ET-1 content were significantly increased in group IR and group IRtR; PaO2 was reduced and PaCQ increased in group IR （P〈0. 05）; PaO2 was reduced （P〈0. 05） and PaCO2 had no significant difference in group IRtR. Compared with group IR, pathological damages of lung tissues, W/D, MPO activity, plasma MDA and ET-1 content and PaCO2 decreased significantly, while PaO2 increased significantly in group IRt R （P 〈 0. 05）. Conclusion Relaxin reduces lung ischemia-reperIusion injury in rats. The mechanism may be associated with decrease in the expression of endothelin, reduction of leukocyte aggregation and prevention of oxygen free radicals damage. No significant effect of relaxin on lung tissue in physiological state was found.