远程缺血预处理对大鼠体外循环后肺损伤的保护作用及机制探讨

Protective effects of remote ischemic preconditioning on lung injury and its mechanism in rats undergoing cardiopulmonary bypass

目的评价远程缺血预处理(RIPC)对大鼠体外循环(CPB)后肺损伤的保护作用并探讨相关机制。方法成年雄性SD大鼠60只,随机分为三组(n=20):假手术组(S组)、CPB组和RIPC+CPB组。S组行麻醉和穿刺但不行CPB;CPB组采用尾动脉插管灌注,右颈静脉插管引流建立CPB模型;RIPC+CPB组在实施CPB前对后肢进行RIPC(通过驱血带阻断后肢血流10 min,复灌10 min,两侧后肢交替进行,每侧进行3次)。麻醉复苏后2 h采集上腔静脉血样,测定血清TNF-α和IL-6浓度,然后处死大鼠取肺组织,测定肺湿/干重比值(W/D比值)、丙二醛(MDA)含量和谷胱甘肽过氧化物酶(GSH-px)活性,光镜下观察病理学改变。结果与S组比较,CPB组和RIPC+CPB组血清TNF-α和IL-6浓度升高,肺组织W/D比值和MDA含量升高,GSH-px活性降低(P<0.05);与CPB组比较,RIPC+CPB组血清TNF-α和IL-6浓度下降,肺组织W/D比值和MDA含量下降,GSH-px活性升高(P<0.05)。HE染色显示RIPC+CPB组肺组织的形态学损伤轻于CPB组。结论 RIPC可减轻大鼠CPB后肺损伤,其机制与抑制炎性反应和脂质过氧化反应有关。

Objective To investigate the protective effects of remote ischemic preconditioning （RIPC） on lung injury and its mechanism in rats undergoing cardiopulmonary bypass （CPB）. Methods Sixty adult male Sprague-Dawley rats were randomly divided into three groups （n=20 each）： sham operation group （group S）, group CPB and group RIPC＋CPB. Rats in group S were anaesthetized and carmulated but did not undergoing CPB; rats in group CPB were cannulated in tail arteries and right jugular vein for CPB; rats in group RIPC＋CPB were subjected to RIPC before CPB. RIPC was used by compressing the two hindlimbs alternately with a tourniquet for three cycles of 10 rain isehaemia followed by 10 min reperfusion. The superior vena cava blood samples were collected at 2 h after anesthesia resuscitation for determination of concentrations of TNF-c~ and IL-6, and pulmonary tissue were obtained to observe the wet to dry weight ratio （W/D ratio）, concentrations of malondialdehyde （MDA） and activity of glutathi- one peroxidase （GSH-px）. The histopathological changes of lung tissue were also examined. Results Compared with group S, the plasma concentrations of TNF-a and IL-6, the W/D ratio and concentrations of MDA in lung tissues were increased, while activity of GSH-px in lung tissues was decreased in group CPB and group RIPC＋CPB （P〈0.05）. Compared with group CPB, the plasma concentrations of TNF-a and IL-6, the W/D ratio and concentrations of MDA in lung tissues were decreased, while activity of GSH-px in lung tissues was increased in group RIPC＋CPB （P〈0.05）. Compared with group CPB, the morphological injury of pulmonary tissue was alleviated in group RIPC＋CPB under HE staining. Conclusion RIPC can reduce the lung injury in rats undergoing CPB. The mechanism is closely related to inhibiting the inflammatory reaction and lipid peroxidation.