高压氧对油酸诱导大鼠急性肺损伤作用的实验研究

目的 探讨高压氧(HBO)对油酸(OA)诱导大鼠急性肺损伤(ALI)的干预作用.方法 80只SD大鼠按随机数字表法分为4组.OA组30只,经鼠尾静脉注射OA 0.15 ml/kg制备ALI模型,分别于制模后4 h、3 d、7 d各随机活杀10只;OA+HBO组20只,在HBO治疗箱给予2.5 atm(1 atm=101.325 kPa)下单次治疗90 min,分别于HBO治疗后3 d、7 d各随机活杀10只;单纯HBO干预组20只,分别于HBO治疗后3 d、7 d各随机活杀10只;另设正常对照组10只.取腹主动脉血进行血气分析,测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6;取左肺标本,观察大体形态改变及镜下病理学改变;取右肺,测定湿/干重(W/D)比值.结果 OA组4 h后动脉血氧分压(PaO2,mm Hg,1 mm Hg=0.133 kPa)由107.70±5.37降至57.40±2.63;肉眼可见肺脏明显淤血、水肿;光镜下肺泡正常结构消失,间质水肿增宽,大量炎性细胞浸润,毛细血管明显扩张、透明膜形成;W/D比值较正常对照组明显增加(6.94±0.44比4.59±0.44,P<0.05),血清TNF-α、IL-1β、IL-6水平升高TNF-α(μg/L):18.52±1.20比5.27±0.61,IL-1β(μg/L):13.73±1.37比6.13±1.51,IL-6(μg/L):14.51±1.21比11.14±0.89].经HBO治疗3 d、7 d时PaO2(mm Hg,3 d:79.20±1.68比59.00±2.70,7 d:94.30±3.77比74.00±3.85)、肺W/D比值(3 d:7.43±0.73比9.82±0.99,7 d:6.75±1.14比8.77±1.60)均较OA组同期有不同程度改善(P<0.05或P<0.01).治疗3 d后HBO有降低血清中IL-1β(μg/L)的作用(6.46±1.99比9.09±1.09,P<0.05).结论 HBO治疗有改善ALI大鼠氧合,促进肺水吸收、抑制部分炎症介质产生的作用.

Effects of hyperbaric oxygen on the acute lung injury induced by oleic acid in rats

Objective To explore the effect of hyperbaric oxygen (HBO) on acute lung injury (ALI) induced by oleic acid (OA) in rats. Methods Eighty healthy Sprague-Dawley (SD) rats were randomly divided into four groups. In OA group (n=30), ALI was produced by injection of OA 0.15 ml/kg through tail vein. Ten rats were randomly selected and sacrificed after injection of OA at the time of 4 hours, 3 days, and 7 days, respectively. In OA plus HBO group (n=20), rats received HBO intervention in a special box with oxygen of 2.5 atm (1 atm=101.325 kPa) for 90 minutes. Ten rats were randomly respectively sacrificed at 3 days and 7 days. In simple HBO group, 20 rats were sacrificed at 3 days and 7 days of HBO intervention, respectively. Other 10 rats were assigned as control group. Blood, lung specimens were collected after sacrifice. Serum contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 were measured. Gross changes and pathological findings of the left lung were recorded. The wet to the dry weigh (W/D) of the right lung was determined. Results Partial pressure of oxygen in arterial blood (PaO2, mm Hg, 1 mm Hg=0.133 kPa) fell from 107.70±5.37 to 57.40±2.63 in OA group. Congestion, bleeding and edema could be seen grossly. They could also be found under microscope with disappearance of normal structure, and accumulation of fluid in interstitium with inflammatory cell infiltration and hyaline membrane formation were also found. Lung W/D ratio was increased as compared with the control group (6.94±0.44 vs. 4.59±0.44, P<0.05). A marked increase was found in serum TNF-α, IL-1β, IL-6 levels TNF-α (μg/L): 18.52±1.20 vs. 5.27±0.61, IL-1β (μg/L): 13.73±1.37 vs. 6.13±1.51, IL-6 (μg/L): 14.51±1.21 vs. 11.14±0.89]. After HBO therapy for 3 days and 7 days, PaO2 (mm Hg, 3 days: 79.20±1.68 vs. 59.00±2.70, 7 days: 94.30±3.77 vs. 74.00±3.85) and lung W/D (3 day: 7.43±0.73 vs. 9.82±0.99, 7 days: 6.75±1.14 vs. 8.77±1.60) of HBO group were ameliorated to varying degrees compared with OA model group (P<0.05 or P<0.01). HBO therapy for 3 days could lower levels of IL-1β (μg/L) in the serum (6.46±1.99 vs. 9.09±1.09, P<0.05). Conclusion It is suggested that HBO treatment for ALI in rats had effects of improving arterial blood gases and the lung water transport, and inhibiting inflammatory mediators production.