降钙素基因相关肽受体对大鼠肺缺血再灌注损伤中核因子-κb表达的影响

Effect of Calcitonin Gene-related Peptide Receptor on Expression of NF-κb in Rat Lung after Ischemia Reperfusion Injury

目的使用降钙素基因相关肽(CGRP)和CGRP受体拮抗剂CGRP8-37研究CGRP受体对大鼠肺缺血再灌注后肺核因子-κb(NF-κb)表达的影响。方法将32只成年健康大鼠随机分为4组:假手术组(S组)、缺血再灌注组(IR组)、CGRP8-37预处理的缺血再灌注组(CGRP8-37组)、CGRP预处理的缺血再灌注组(CGRP组)。再灌注末抽取动脉血进行血气分析,观察动脉血氧分压(PaO2)及肺泡动脉氧分压差(A-aDO2)的变化,同时取肺组织以RT-PCR法检测NF-κb mRNA的表达,并用光学显微镜观察再灌注后肺组织病理学变化。结果与假手术组比,缺血再灌注降低PaO2,增加A-aDO2,上调NF-κb mRNA的表达(P<0.05),加重肺的组织病理损伤;与IR组比较,CGRP预处理可改善肺的气体交换功能,降低NF-κb mRNA的表达(P<0.05),同时减轻缺血再灌注引起的病理学损伤;CGRP8-37预处理的作用则相反。结论 CGRP受体在肺缺血再灌注损伤中可能通过下调NF-κb而发挥保护作用。

Objective To study the effect of calcitonin gene-related peptide （CGRP） receptor on the expression of nuclear factor-κb （NF-κb） in rat lung after ischemia reperfusion injury. Methods Thirty-two adult male Sprague Dawley rats were divided into four groups （8 per group） as follows., sham group （sham thoracotomy）, IR group （occlusion of the left pulmonary hilus for 0.5 h followed by reperfusion for 4 h）, another two groups were pretreated with CGRP or CGRPS-37 （a CGRP receptor antagonist）. Arterial blood was collected at the end of reperfusion to test blood gas, arterial oxygen pressure （PaO2） and alveolar arterial oxygen difference （A-aDO2）. Lung tissue was collected to measure the expression level of NF-κb mRNA by using RT-PCR. Light microscopic changes of lung tissue were also examined. Results Compared with sham group, rats in the IR group had poorer gas exchange （lower PaO2, higher A-aDO2 ）, upregulation of NF-κb mRNA expression （P〈0.05） and more severe histological injury. Pretreatment with CGRP improved gas exchange function, significantly decreased NF-κb mRNA expression （P〈0. 05 versus IR and CGRP837 groups）. Administration of CGRP also attenuated IR-induced pathological lesions. The pretreatment of CGRP8-37 showed the opposite results to those of CGRP. Conclusion CGRP receptor plays an important protective role in lung IR injury, which is closely related to the downregulation of NF-κb mRNA.