FTY720通过抑制脑组织IL-23表达减轻脑缺血再灌注损伤

FTY720通过抑制脑组织IL-23表达减轻脑缺血再灌注损伤孙伟;苏志强;张帅;丁兆明;宋丽
【期刊名称】《中国神经免疫学和神经病学杂志》
【年(卷),期】2011(18)5
【摘要】目的观察大鼠局灶性脑缺血再灌注(I/R)模型脑组织白细胞介素-23(IL-23)水平变化,观察1-磷酸鞘氨醇(S1P) 受体激动剂芬戈莫德(fingolimod,FTY720)对
IL-23表达及脑I/R损伤的影响,探讨IL-23和FTY720在脑I/R损伤中的作用.方法将雄性Wistar大鼠随机分成假手术组和I/R组,后者再分为I/R 3 h、6 h、12 h、24 h、24 h+安慰剂和24 h+FTY720六个亚组.应用"线栓法"制作大鼠右侧大脑中动脉闭塞模型,2 h后拔出线栓进行再灌注,并分别于再灌注3、6、12、24 h处死大鼠.I/R 24 h+安慰剂组和I/R 24 h+FTY720组大鼠分别于再灌注前10 min经尾静脉按体质量1 mg/kg注入安慰剂和FTY720.利用免疫组化方法观察大鼠脑组织IL-23表达水平变化,以2,3,5-氯化三苯基四氮唑(TTC)染色法测定大鼠相对脑梗死体积和TUNEL阳性细胞计数,并比较I/R 24 h +安慰剂组和I/R 24 h+FTY720组大鼠神经功能评分.结果假手术组大鼠脑组织无IL-23表达,I/R 3 h、6 h、12 h和24 h组大鼠梗死灶周围区皮质IL-23阳性细胞数依次为5.16±0.68、5.54±1.06、23.72±3.11和97.20±10.26,I/R 各时间组间差异有统计学意义(P<0.05).I/R 24 h+安慰剂组大鼠神经功能评分、相对梗死体积、凋亡细胞数、IL-23阳性细胞数分别为2.37±0.27、(14.7±3.40)%、19.00±2.10、101.75±12.04,I/R 24
h+FTY720组分别为1.31±0.21、(5.50±2.62)%、9.05±1.25、54.96±7.82,二组间比较差异均有统计学意义(均P<0.05).结论 IL-23在脑I/R过程中表达水平上调,加重I/R损伤.FTY720可能通过抑制IL-23的表达发挥脑保护作用.%Objective To
observe the expression of IL-23 in rats with focal brain ischemia-reperfusion (I/R), and the effect of FTY720 on the expression of IL-23 and brain I/R injury. To clarify the effects of IL-23 and FTY720 in brain I/R injury. Methods Male Wistar rats were randomly divided into the sham-operated group and the I/R groups. The I/R groups were divided into 6 subgroups, including I/R 3 h, 6 h, 12 h, 24 h, 24 h+ vehicle and 24 h+FTY720. The model of focal brain I/R injury was induced by middle cerebral artery occlusion (MCAO). After 2 hours of ischemia and 3, 6, 12 and 24 hours of reperfusion, the animals were sacrificed. Ten minutes prior to reperfusion, animals suffered with 24-hour reperfusion were treated intravenously with vehicle or FTY720 (1 mg per kg body weight), which was the agonist of sphingosine 1-phosphate (sip) receptors. Immunohistochemistry was used to detect the level of IL-23 protein expressions. Neurological score, TTC and TUNEL were used to detect the effect of FTY720. Results In brains of the sham-operated group, IL-23-positive cells were not observed. Meanwhile, the number of IL-23-positive cells in the peri-infarct cortex surrounding the primary infarct were 5. 16±0. 68, 5. 54±1. 06, 23. 72±3. 11 and 97. 20±10. 26 respectively 3 h, 6 h, 12 h and 24 h after reperfusion (P<0. 05). After 24 h reperfusion, the number of IL-23-positive cells, neurological score, relative infarct volume and the count of TUNEL-positive cells were 2. 37±0. 27, (14. 7±3.40)%, 19.00±2. 10 and 101.75±12.04 respectively in animals treated with vehicle, and were 1.31±0.21, (5.50± 2.
62)%, 9. 05±l. 25 and 54. 96±7. 82 in animals treated with FTY720 (P<0. 05, respectively). ConclusionsThis study indicates that FTY720 may exert
neuroprotective effects by reducing the expression of cerebral IL-23 during the course of focal brain I/R.
【总页数】5页(P347-351)
【作者】孙伟;苏志强;张帅;丁兆明;宋丽
【作者单位】150001,哈尔滨医科大学附属第一医院神经内科;150001,哈尔滨医科大学附属第一医院神经内科;150001,哈尔滨医科大学附属第一医院神经内
科;150001,哈尔滨医科大学附属第一医院神经内科;150001,哈尔滨医科大学附属第一医院神经内科
【正文语种】中文
【中图分类】R743.31
【相关文献】
1.FTY720通过激活CaMKK/Akt通路减轻全脑缺血再灌注损伤 [J], 许静;刘志安;高殿帅
2.丹皮酚抑制大鼠局灶性脑缺血再灌注损伤脑组织细胞间黏附分子-1和血管细胞黏附分子-1的表达 [J], 张硕;高海青;张岫美
3.髓鞘相关生长抑制因子Nogo-A及胰岛素样神经生长因子受体在局灶性脑缺血再灌注损伤后大鼠脑组织的表达特征 [J], 刘广义;王娜;刘红
4.白芍总苷通过抑制内质网应激减轻大鼠脑缺血再灌注损伤的实验研究 [J], 代小兰;竺东杰;陈小丽;李红霞
5.马赛替尼通过抑制自噬和细胞凋亡减轻脑缺血/再灌注损伤 [J], 王燕;平锋锋;周丹丽;陈艳华;凌菁菁
因版权原因，仅展示原文概要，查看原文内容请购买。