目的 探讨促红细胞生成素（erythropoietin，EPO）对大鼠肠缺血再灌注后肺损伤的保护作用及基质金属蛋白酶-9（MMP-9）和半胱氨酸水解酶-1（Caspase-1）表达的影响。 方法 雄性SD大鼠30只随机分为5组（n=6），缺血再灌注损伤组（IIR组）、1000 U/kg EPO低剂量（L组）、3000 U/kg EPO中剂量组（M组）、5000 U/kg EPO高剂量组（H组）和假手术组（S组）。IIR组、L、M和H组行夹闭肠系膜上动脉1 h，再灌注0.5 h。处理组于缺血前1 h，分别以1000、3000和5000 U/kg EPO腹腔注射，IIR组及S组给予等量生理盐水。观察大鼠肺组织的病理变化。免疫组化染色和Western blot法检测MMP-9，Caspase-1蛋白表达。 结果 （1）光镜下IIR组肺泡结构破坏，炎性细胞浸润，肺间质水肿。EPO预处理组肺组织结构病变程度较IIR组明显减轻，其中M组较L组和H组明显减轻。（2）免疫组织化学染色及Western blot检测结果显示，与S组比较，缺血再灌注各组肺组织MMP-9和Caspase-1表达水平均上升（P<0.01）。EPO不同剂量组间比较，M组大鼠肺脏MMP-9和Caspase-1表达水平较L、H组降低（P<0.05）。 结论 EPO可减轻大鼠肠缺血再灌注后肺损伤，该作用可能与抑制MMP-9、Caspase-1介导的过度炎症反应有关。
Objective To investigate the protective effects of erythropoietin (EPO) on lung injury after rat intestinal ischemia reperfusion. Methods Thirty male SD rats were divided into 5 random groups (n=6 each): an intestinal ischemia reperfusion group (IIR group), a 1000 U/kg EPO treated (low dosage EPO group), a 3000 u/kg EPO treated (middle dose-EPO group), a 5000 U/kg EPO treated (high dose-EPO group) and a sham-operation group (S group). The intestinal ischemia reperfusion model were established by clamping superior mesenteric artery for 1 hour and reperfusion for half an hour. The three treated groups were administrated with intraperitoneal injection of 1000 U/kg, 3000 U/kg and 5000 U/kg EPO 1 hour before reperfusion. Lung tissues was observed by HE staining. The protein levels of MMP-9 and Caspase-1 in the liver tissues were detected by immunohistochemical staining and Western blot. Results (1) In the IIR group, lung injury was induced by IIR, characterized as histological damage of edema, hemorrhage and neutrophil infilitration, which could be alleviated by EPO. (2)The immunohistochemistry and Western blot results showed that compared with the Sham group, the expression of active MMP-9 and Caspase-1 in the IIR group was increased; after EPO intervention, the MMP-9 and Caspase-1 was decreased. Compared with the L and H groups, the expression of MMP-9 and Caspase-1 in the M group was lower than that of the L and H group (P<0.05). Conclusion EPO has the protective mechanism on lung damage after rat intestinal ischemia reperfusion. The protective mechanism of EPO may be related to the inhibition of MMP-9 and Caspase-1 which mediated over-inflammation.
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