Yun Wu, Qing-Cheng Liang, Lei Yang, Jia-Yin Miao
Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
J Neuroimmunol. 2008 Dec 15;205(1-2):73-9. doi: 10.1016/j.jneuroim.2008.09.006. Epub 2008 Oct 19.
To study the effect of mucosal toleration to E-selectin on cerebral ischemia-reperfusion injury in rats and associated mechanisms.
Rats were exposed to intranasal administration of E-selectin or PBS every other day for 10 days (single-tolerization group) or on two tolerization schedules separated by 11 days (booster-tolerization group). Control group received middle cerebral artery occlusion (MCAO) only. MCAO was performed 48 h after the last dose of E-selectin or PBS. After 2 h ischemia and 22 h reperfusion, the rats were killed. We examined the regional cerebral blood flow, neurological testing, frequencies of CD4+ T and CD8+ T lymphocytes in blood, plasma SOD activity, infarct volumes, and mRNA expressions of IL-10, TGF-beta(1), E-selectin, ICAM-1 and LFA-1 in the ischemic brain tissues.
There were 30.25% (P<0.05) decreases of infarction volumes in the E-selectin booster group accompanied by decreased neurological deficit scores compared with PBS group. Compared with PBS-treated rats, CD8-positive cells were significantly decreased (27.4%, P<0.05), CD4-positive cells tended to increase (P>0.05), SOD activity was obviously increased (P<0.05), mRNA levels of IL-10 were markedly increased (21.0%, P<0.05) and TGF-beta(1) showed an upward trend (6.2%, P>0.05), mRNA levels of E-selectin were prominently decreased (28.7%, P<0.01) and ICAM-1 and LFA-1 had downward trends (P>0.05) in E-selectin booster animals.
Mucosal tolerance to E-selectin after booster tolerization could relieve cerebral ischemia-reperfusion injury and induce ischemia tolerance in Wistar rats. The mechanisms may involve decreased frequencies of CD8+ T cells in blood, increased plasma SOD activity, heightened mRNA expression of IL-10 and lowered mRNA expression of E-selectin in the ischemic hemisphere.
研究对E选择素的黏膜耐受对大鼠脑缺血再灌注损伤的影响及其相关机制。
大鼠每隔一天经鼻给予E选择素或磷酸盐缓冲液（PBS），共10天（单次耐受组），或按两个耐受方案给药，间隔11天（加强耐受组）。对照组仅进行大脑中动脉闭塞（MCAO）。在最后一剂E选择素或PBS给药48小时后进行MCAO。缺血2小时和再灌注22小时后，处死大鼠。我们检测了局部脑血流量、神经功能测试、血液中CD4⁺T和CD8⁺T淋巴细胞频率、血浆超氧化物歧化酶（SOD）活性、梗死体积以及缺血脑组织中白细胞介素10（IL-10）、转化生长因子β1（TGF-β1）、E选择素、细胞间黏附分子1（ICAM-1）和淋巴细胞功能相关抗原1（LFA-1）的mRNA表达。
与PBS组相比，E选择素加强组梗死体积减少30.25%（P<0.05），神经功能缺损评分降低。与PBS处理的大鼠相比，E选择素加强组动物血液中CD8阳性细胞显著减少（27.4%，P<0.05），CD4阳性细胞有增加趋势（P>0.05），SOD活性明显增加（P<0.05），IL-10的mRNA水平显著升高（21.0%，P<0.05），TGF-β1呈上升趋势（6.2%，P>0.05），E选择素的mRNA水平显著降低（28.7%，P<0.01），ICAM-1和LFA-1呈下降趋势（P>0.05）。
加强耐受后对E选择素的黏膜耐受可减轻Wistar大鼠的脑缺血再灌注损伤并诱导缺血耐受。其机制可能涉及血液中CD8⁺T细胞频率降低、血浆SOD活性增加、缺血半球中IL-10的mRNA表达升高以及E选择素的mRNA表达降低。
