【摘要】 目的:探讨促红细胞生成素(EPO)对大鼠肝缺血再灌注损伤后的保护作用及对肝基质金属蛋白酶-9(MMP-9)和半胱天冬酶-1(caspase-1)表达的影响。方法:将健康雄性SD大鼠随机分为5组,缺血再灌注损伤组(I/R)、促红细胞生成素低剂量组(L组)、中剂量组(M组)、高剂量组(H组)和假手术组。H-E染色观察各组肝组织的病理变化;免疫组织化学显色和免疫印迹法检测MMP-9、caspase-1蛋白表达;比色法检测血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平。结果:光镜下I/R组肝细胞出现水肿及片状坏死,大量炎性细胞浸润;EPO预处理组出现肝细胞水肿、坏死及炎细胞浸润程度明显减轻。与假手术组比较,缺血再灌注各组肝组织MMP-9和caspase-1表达水平均上升,血清ALT和AST水平也均上升,且均以I/R组上升最为明显。EPO不同剂量组间比较,中剂量组大鼠肝MMP-9和caspase-1表达水平、ALT和AST的水平与低、高剂量组比较均降低。结论:EPO对大鼠肝缺血再灌注损伤具有保护作用,最佳浓度是3000U/kg。该保护作用可能与抑制MMP-9、caspase-1介导的过度炎症反应有关。更多还原

【Abstract】 Objective:To study the effect of erythropoietin(EPO)on hepatic ischemia reperfusion injury and the expression of hepatic matrix metalloproteinase 9(MMP-9)and cysteinyl aspartate specific proteinase-1(caspase-1).Methods:Fifty healthy male SD rats were randomly divided into 5 random groups:ischemia reperfusion group(I/R group),low-dose EPO group(L group),middle-dose EPO group(M group),high-dose EPO group(H group)and sham-operation group(sham group).The morphologic changes in the liver were observed by light microscope after H-E staining.The protein levels of MMP-9 and caspase-1 in the liver tissues were detected by immunohistochemical staining and Western blotting.Serum alanine transaminase(ALT)and aspartate aminotransferase(AST)levels were measured by methods recommended by the manufacturer.Results:Under light microscope,there were edema and necrosis of hepatocytes and a large number of inflammatory cell infiltration in I/R group.Meanwhile,necrosis and infiltration of inflammatory cells in EPO preconditioning group were significantly alleviated.Compared with the control group,the expression value of MMP-9 and caspase-1 in the liver and the activity of ALT and AST in serum of the other four groups increased(P<0.01),and the I/R group showed the most significant change.Compared with L and H groups,the expression of MMP-9 and caspase-1 in the liver of M group was lower than that of L and H groups.Conclusion:EPO has the protective effect on hepatic ischemia-reperfusion injury in rats and the best concentration is 3000 U/kg.The protective mechanism of EPO may be related to the inhibition of MMP-9 and caspase-1 which mediates over-inflammation.更多还原