不同剂量雌激素对大鼠脑缺血-再灌注后ICAM-1,TNF-α表达的影响

Effect of different dosed estrogen on expression of intercellular adhesion molecule-1 and tumor necrosis factor-after focal cerebral ischemia/reperfusion in rats

目的:探讨不同剂量雌激素对雄性大鼠脑缺血-再灌注损伤后脑保护作用及其可能的机制.方法:选用雄性SD大鼠200只,体质量250～300 g,随机分为5大组:假手术组(SO组),缺血-再灌注组(I/R组),雌激素大剂量组(EC组)、中剂量组(EB组)、小剂量组(EA组)、雌激素治疗组(E2组),每组大鼠40只.应用免疫组化法测定大鼠大脑皮质ICAM-1,TNF-α表达情况.采用两样本均数的t检验对数据进行分析.结果:大鼠200只均进入结果分析,I/R组各时间点ICAM-1,TNF-α的表达24 h峰值分别为(94.62±5.72),(41.68±2.46),高于SO组[(2.32±0.41),(1.88±0.28),P<0.01]和E2各剂量治疗组[(68.28±4.14),(39.35±6.63),(40.90±6.09)和(19.22±0.96),(11.92±1.36),(12.75±1.03),P<0.05].在E2组各剂量组中在3,24,48 h,雌激素EA组的表达高于EB及EC组(P<0.05);EB,EC组间在各灌注时间点差异无统计学意义.在表达时间上,I/R组和E2组缺血2 h再灌注3 h即有ICAM-1开始表达,在12 h明显升高,24 h达到高峰.结论:雌激素可能通过抑制TNF-α的激活,减少ICAM-1的表达起到脑保护的作用,且雌激素的脑保护作用呈一定的量效关系.

AIM： To study the neuroprotective role of different dosed estrogen on expressions of ICAM-1 and TNF-α after focal cerebral ischemia/reperfusion in male rats. METHODS： Totally 200 male SD rats, with the body mass of 250-300 g, were selected and randomly assigned into 5 groups： Sham operation group （ SO ） , isehemia reperfusion group （I/R） , low-dosage estro- gen treatment group （ EA ）, medium-dosage estrogen treatment group（EB） and high-dosage estrogen treatment group （ EC ）. The expression of ICAM-1 and TNF-α was detected by immnnohisto- chemistry. Data in all groups were analyzed with test. RESULTS ： The data of the 200 rats were analyzed. The expres- sion of ICAM-1 and TNF-ct in the I/R group（94.62 ± 5.72） and （41.68 ±2.46） were higher than those in the SO group（2.32 ± 0.41 and 1.88 ± 0.28 ） and treatment groups （68.28 ± 4.14） , （39.35 ±6. 63）, （40. 90 ＋6. 09） and （19. 22 ±0. 96）, （11.92 ± 1.36） , （ 12.75 ± 1.03） , respectively. The estrogen level in EA group was significantly higher than those in the EB group and EC group （ P 〈 0.05 ） , but there was no significant difference between the EB group and the EC group （ P 〉 0.05 ）. The ICAM-1 expression was observed on cerebral cortex in I/R group and different treatment groups after 2-hour cerebral ischemia and 3-hour reperfusion. The expression increased significantly after 12 th and reached the peak at 24 th. CONCLUSION： Estrogen may exert some neuroprotective effect against the cerebral ischemia in rats by inhibiting the activation of TNF-α and decreasing the expression of ICAM-1. The neuroprotective effect of estrogen is closed related to its dosage.