允许性高碳酸血症对大鼠肢体缺血再灌注肺损伤的影响

摘要

Objective To observe the protective effects of permissive hypercapnia on lung injury induced by ischemia-reperfusion of hind limbs in rats. Methods A total of 30 male SD rats were randomly divided into the sham-operated group (SH group), the ischemia reperfusion group (IR group), and the permissive hypercapnia-isch-emia-reperfusion group (PHC-IR group), with 10 rats in each group. PHC-IR group was treated with hypercapnic ventila-tion mode after general anesthesia (inhalation of 10%CO2+90%air-gas mixture) for 3 hours, so that the rats' blood Pa-CO2 was maintained at 60~80 mmHg. The remaining two groups received general ventilation mode (air) for 3 hours. IR group and PHC-IR group established ischemia reperfusion injury model, isolated femoral artery, and block double side for 4 hours (before reperfusion). After blood flow was recovered and observed for 4 hours (after reperfusion), SH group only underwent surgery separation femoral artery. Artery blood gas analysis was recorded before mechanical ventilation, mechanical ventilation for 3 hours, before reperfusion, and after reperfusion. After rats were killed, the left lower lobe of the lung tissue was removed, the Wet/Dry weight ratio was determined, tumor necrosis factor (TNF)-αand interleukin (IL)-8 levels in lung tissue were measured by enzyme-linked immunosorbent assay. Results Compared with IR group, the PaO2 value of PHC-IR group significantly increased after reperfusion ((70.7 ± 6.8) mmHg vs (60.7 ± 4.9) mmHg, P<0.05);W/D ratio in lung tissue of rats in the PHC-IR group was significantly reduced ((4.86 ± 0.53) vs (5.64 ± 0.74), P<0.05). There was dilated congestive lung capillaries, the alveolar interstitial edema and inflammatory cell infiltration in IR group;but in SH group and PHC-IR group, alveolar structure were more complete, interstitial pulmonary edema of al-veolar exudate were reduced. TNF-αand IR IL-8 levels in PHC-IR group were significantly decreased than IR group ((0.44±0.06) µg/L vs (0.83±0.18) µg/L;(28.3±2.6) µg/L vs (33.4±3.8) µg/L, P<0.05). Conclusion The permissive hy-percapnia reduced lung injury induced by ischemia-reperfusion of hind limbs in rats and its mechanism may be relat-ed to inhibiting the inflammatory response.%目的：研究允许性高碳酸血症对大鼠肢体缺血再灌注肺损伤的影响。方法30只SD大鼠，按随机数字法将大鼠随机分为假手术组(SH组)、缺血再灌注组(IR组)和允许性高碳酸血症-缺血再灌注组(PHC-IR组)，每组各10只。经腹腔全麻后对PHC-IR组实行高碳酸通气模式（吸入10%CO2+90%空气混合气体)3 h，使该实验组大鼠血气PaCO2达到并维持于60~80 mmHg。其余两组，吸空气3 h。IR组和PHC-IR组建立缺血再灌注模型，分离股动脉后阻断双侧股动脉血流4 h后(再灌前)，松夹，恢复血流后观察4 h (再灌后)，SH组仅手术分离双侧股动脉，记录各组大鼠机械通气前、机械通气后3h、再灌注前、再灌注后的血气分析。后处死大鼠，取左肺下叶组织，行肺湿干值(W/D)测定，光镜下观察肺组织形态，采用酶联免疫吸附法测定肺组织中肿瘤坏死因子(TNF)-α和白细胞介素(IL)-8的水平。结果再灌注后PHC-IR组PaO2值为(70.7±6.8) mmHg，较IR组的(60.7±4.9) mmHg明显升高，差异有统计学意义(P<0.05)；PHC-IR组大鼠肺组织W/D值为(4.86±0.53)，明显低于IR组的(5.64±0.74)，差异有统计学意义(P<0.05)；IR组大鼠肺毛细血管扩张充血，肺泡间质水肿，并有炎性细胞浸润；SH组和PHC-IR组大鼠的肺泡结构较完整，肺间质肺泡腔渗出水肿较IR组减轻。PHC-IR组大鼠肺组织中TNF-α为(0.44±0.06)µg/L，IL-8为(28.3±2.6)µg/L，均明显低于IR组的(0.83±0.18)µg/L和(33.4±3.8)µg/L，差异均有统计学意义(P<0.05)。结论允许性高碳酸血症可以减轻大鼠肢体缺血再灌注肺损伤，其机制可能与抑制炎性反应有关。