缺血后处理对大鼠局灶性脑缺血再灌注损伤时TLR4信号通路表达的影响

目的：观察缺血后处理对大鼠局灶性脑缺血再灌注损伤后TLR4通路表达的影响。方法：成年健康雄性SD大鼠110只，随机分为假手术组（sham组）（n=10）、缺血再灌注组（I／R组）和后处理组（IP组），后两组又依据缺血再灌注6h、12h、24h、48h、72h不同的时间点再分五个亚组。对各组行神经行为学评分，脑组织梗死体积测量，TUNEL技术检测神经细胞凋亡的情况，免疫组织化学技术观察各组大鼠脑组织TLR4、NF—KB和TNF—a蛋白的表达，原位杂交方法检测各组大鼠脑组织TLR4mRNA、NF-KBmRNA的表达。结果：缺血后处理可下调TLR4、NF-KB、TNF-a细胞炎性因子的表达，抑制细胞凋亡、减少脑梗死体积，改善神经行为。结论：后处理可通过抑制TLR4信号通路表达，减少脑梗死体积，改善神经功能。

Effects of Ischemic Postconditioning on TLR4 Signaling Pathway During Focal Cerebral Ischemla/Reperfusion in Rats

Objective：To investigate the effect of ischemic postconditioning on TLR4 signaling pathway during focal cerebral ischemic reperfusion in rats. Methods： One hundred and ten adult healthy male Sprague-Dawley rats were randomly divided into sham group（n=10）, ischemiaJreperfusion group and ischemic postconditioning group. The latter groups was equally divided into five subgroups according to different time points of the ischemia-reperfusion （6,12,24,48, and 72 h）（n=l 0）, The models of focal brain ischemia were established by intraluminal thread middle cerebral artery occlusion （MCAO） methods. For IP, the rats were subjected to 3 cycles of 15-second/15-second reperfusion/reocclusion after 2 h MCAO. Each group was evaluated with examinating neurobehavioral fimction deficit scores and infarct volume. The apoptotic cells were counted by TUNEL method. The immtmohistochemistry stain was used to determine the expressions of TLR4, NF-K B and tumor necrosis factor-a （TNF-ct）. The levels of TLR4mRNA and NF-K BmRNA were examined by In Situ Hybridization （ISH）. Results： Ischemic postconditioning could down-regulate the expressions ofTLR4, NF-K B and TNF-a, inhibit apoptosis, reduce the cerebral infarct volumes, and improve the neurobehavioral function of rats. Conclusions： IP could reduce the infarct volumes and improve neurobehavioral function through inhibiting the expressions of TLR4 signaling pathway.