DADLE对大鼠急性全脑缺血再灌注损伤脑组织ERK信号转导通路影响的研究

Impact of DADLE on ERK signal transduction pathway in brain tissue in mrs with acute global cerebral is-chemia-repeofusion injury

目的探讨DADLE对急性全脑缺血再灌注损伤大鼠脑组织中ERK信号转导通路的影响及其与脑保护作用的关系。方法将健康雌性SD大鼠50只（1800220g）随机分为5组：假手术组（Sham，n=10）：只暴露血管而不夹闭；缺血再灌注组（I／R，n=10）：采用改良的二血管阻断加低血压法建立全脑缺血再灌注模型，缺血15min后再灌注120min；DADLE处理组分为DADLE2mg／kg组（A，n=10）、DADLE3mg／kg组（B，n=10）和DADLE5mg／kg组（C，n=10）：在FR组的基础上于再灌注前经颈外静脉注射DADLE。HE染色观察各组海马CAl区神经元病理变化情况，westernblot测其脑组织内非磷酸化ERK与磷酸化ERK（P-ERK）的表达状况。结果Sham组ERK与P-ERK蛋白表达水平显著低于其他各组（P〈0．05）；DADLE处理组与I／R组相比，ERK、P-ERK蛋白的表达水平上调（P〈0．05），其中B组、C组ERK与P-ERK蛋白表达水平显著高于A组（P〈0．05），而B组、C组之间ERK、P-ERK表达则无显著性差异（P〉0．05）。结论在急性大鼠全脑缺血再灌注损伤中，ERK信号转导通路的活性明显上调，DADLE可以通过增加ERK的活化而达到降低神经元细胞的损伤，发挥脑保护的作用；同时，该作用呈剂量相关性和有“天花板效应”。

Objective To investigate the impact of DADLE on ERK signal transduction pathway in brain tissue in rats with acute global cerebral ischemia-reperfusion injury and the association of DADLE with cerebral protection. Methods Fifty female Sprague-Dawley rats （ 180-220 g） were randomly divided into 5 groups. Is- chemia/reperfusion group （I/R, n = 10） was induced by bilateral common artery occlusion combined with hy- potension for 15-minute global ischemia followed by 120-minute reperfusion; sham group （Sham, n = 10） ex- posed bilateral common artery without occlusion; DADLE group was subdivided into DADLE of 2 mg/kg group （A, n = 10）, DADLE of 3 mg/kg group （B, n = 10）, and DADLE of 5 mg/kg group （C, n = 10）. DADLE was applied through external jugular vein before reperfusion. Neuropathological changes in hippocampus CAI area were detected by Hernatoxylin-Eosin （H-E） staining; and the expressions of ERK and phosphorylated ERK （p-ERK） in brain tissue were determined by Western blot. Results Expression levels of ERK and p-ERK were significantly lower in sham group than in I/R group and DADLE group （P〈0.05）. And the expression levels of ERK and p-ERK were increased in DADLE group as compared with I/R group （P〈0.05）. Among the DADLE subgroups, the expression levels of ERK and p-ERK were higher in groups B and C than in group A, but no sta- tistical difference was found between group B and group C. Conclusions DADLE activates ERK signal trans- duction pathway in brain tissue in rats with acute global cerebral ischemia-reperfusion injury and reduce neu-ronal cell damage. Tthe neuroprotective action of DADLE is dose-related and has ＇ceiling effect＇.