允许性高碳酸血症对大鼠肢体缺血再灌注肺损伤的影响

Protective effects of permissive hypercapnia on lung injury induced by ischemia-reperfusion of hind limbs in rats

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6080 mm Hg。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3 h、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）mm Hg,较IR组的（60.7±4.9）mm Hg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。

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-ischemia-reperfusion group(PHC-IR group), with 10 rats in each group. PHC-IR group was treated with hypercapnic ventilation mode after general anesthesia(inhalation of 10% CO2+90% air-gas mixture) for 3 hours, so that the rats' blood PaCO2 was maintained at 60~80 mm Hg. 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)-α and interleukin(IL)-8 levels in lung tissue were measured by enzyme-linked immunosorbent assay. Results Compared with IR group,the Pa O2 value of PHC-IR group significantly increased after reperfusion((70.7 ± 6.8) mm Hg vs(60.7 ± 4.9) mm Hg, 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 alveolar exudate were reduced. TNF-α and 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 hypercapnia reduced lung injury induced by ischemia-reperfusion of hind limbs in rats and its mechanism may be related to inhibiting the inflammatory response.