血管紧张素转化酶2在海水淹溺诱导大鼠急性肺损伤中的作用

Therapeutic Effect of Angiotensin-Converting Enzyme 2 on Rats with Experimental Pulmonary Edema after Seawater Drowning

目的探讨血管紧张素转化酶2(ACE2)在海水淹溺诱导大鼠急性肺损伤(PE-SWD)中的治疗作用。方法 24只Wistar大鼠随机分为三组:手术对照组(C组)、海水淹溺组(S组)和ACE2治疗组(T组)。S组用气管吸入海水法建立模型;C组除不吸入海水外,其他处理同S组;T组在海水吸入后,立即给予腹腔注射重组大鼠ACE2 0.1 mg/kg。于术后3 h取大鼠腹腔动脉血,全自动动脉血气分析仪测定大鼠动脉血气;测大鼠肺组织湿重/干重(W/D)比值;使用酶联免疫吸附试验法(ELISA)测定各组大鼠肺组织中IL-8含量;光学显微镜观察肺组织病理形态学改变。结果成功复制了大鼠海水淹溺型肺损伤模型;S组PaO2显著低于C组[(52.34±2.69)mm Hg比(96.40±3.47)mm Hg,P<0.05],T组PaO2显著高于S组[(64.58±3.42)mm Hg比(52.34±2.69)mm Hg,P<0.05];S组W/D比值显著高于C组[(8.30±0.24)比(4.49±0.19),P<0.05)],T组显著低于S组[(5.65±0.25)比(8.30±0.24),P<0.05)];S组IL-8值显著高于C组[(1112.2±40.02)比(440.39±4.06,P<0.05)],T组显著低于S组[(858.56±9.92)比(1112.2±40.02),P<0.05);光镜下可见S组肺组织有肺泡腔内出血及透明膜形成,肺泡水肿及肺间质水肿;T组肺泡水肿及肺间质水肿有所减轻;C组未见明显病理变化。结论吸入海水可使大鼠肺组织损伤明显。ACE2对海水淹溺性肺水肿有治疗作用,其作用可能是对IL-8的影响而产生的。

Objective To explore the therapeutic effect of angiotensin-converting enzyme 2 （ACE2） on pulmonary edema after sea-water drowning. Methods Twenty-four Wistar rats were randomly divided into 3 groups,/e, a control group, a seawater drowning group, and an ACE2 treatment group. The rats in the seawater drowning group and the ACE2 treatment group were infused sea-water into their lungs. Then the rats in the ACE2 treatment group were intraperitoneally injected with recombinant rat ACE2. All rats were killed at the time point of 3 hours. Rat arterial blood gas was analyzed and wet/dry weight ratio of lung tissue was measured. The IL-8 content in lung tissue was measured with enzyme linked immunosorbent assay. Pathological changes of lung tissue were observed under light microscope. Results Acute lung injury induced by seawater drowning was successfully reproduced in the rats. The PaO2 in the seawater drowning group was significantly lower than that in the control group and the ACE2 treatment group [ （52. 34 ±2. 69） mm Hg vs. （96. 40 ± 3.47 ） mm Hg and （64. 58 ± 3.42 ） mm Hg, P 〈 0. 05 ]. The lung W/D ratio and IL-8 level in the seawater drowning group were significantly higher than those in the control group and the ACE2 treatment group （8. 30 ± 0. 24 vs. 4. 49 ± 0. 19 and 5.65 ± 0. 25, P 〈 0. 05 ; 1112. 2± 40.02 vs. 440. 39± 4. 06 and 858. 56±9. 92, P 〈0.05）. Lung pathological examination revealed hemorrhage and hyaline membrane formation, alveolar and interstitial edema in the seawater drowning group while those changes significantly relieved in the ACE2 treatment group. Conclusion ACE2 treatment has therapeutic effects on acute lung injury induced by seawater drowning.