大鼠蛛网膜下腔出血后NLK在基底动脉壁的表达变化

目的探讨大鼠蛛网膜下腔出血（subamchnoidhemorrhage，SAH）后Nemo样激酶（nemo—likekinase，NLK）在基底动脉壁中的表达变化及其与脑血管痉挛（cerebralvasospasm，CVS）的关系。方法60只健康成年SD大鼠随机分为对照组（NS组）和SAH组，SAH组又分为1d、3d、5d、7d和14d5个亚组各10只大鼠。应用枕大池一次注血法制成SAH动物模型；通过HE染色光镜下观察基底动脉的病理学变化，测定血管壁厚度及血管腔内径，计算出不同时期的基底动脉血管腔横截面积，以此评价脑血管痉挛；并应用免疫组化法及Westernbolt评估大鼠基底动脉管壁NLK在不同时间点的表达。结果HE染色显示SAH组大鼠基底动脉管腔狭窄，内膜皱褶，平滑肌细胞肥大，3d时病理学变化最显著，管腔狭窄明显，血管腔横截面积约为对照组的43．5％，且管壁明显增厚，约为对照组的1．7倍，之后狭窄程度逐渐减轻，14dfl~接近正常。SAH后基底动脉壁NLK逐渐减少，表达低谷为注血后3d，随后开始表达增加，14d基本恢复至正常水平。结论通过构建大鼠枕大池一次注血模型，能够观察到基底动脉发生明显的细胞形态改变、管壁的增厚及管腔的狭窄，提示SAH后存在CVS；SAH后NLK在基底动脉壁的表达先下降后上调，并与CVS的时相基本一致，提示NLK可能参与CVS的病理过程。

Objective To explore the change of the expression of nemo-like kinase （NLK） in basilar arterial wall and its relationship with cerebral vasospasm（CVS）after subarachnoid hemorrhage（SAH）. Methods 60 adult healthy SD rats were randomly divided into tv^o groups, the SAH group and control group（NS group）, rats in SAH group were subdivided into 5 subgroups：ld, 3d, 5d, 7d and 14d groups,with 10 rats in each group. SAH animal model were made by once blood injection through cisterna magna. The pathological changes of basilar arterial wall were observed after HE staining. The thickness of arterial wall,the diameter of the artery were measured and the lumen cross-sectional area was calculated to evaluate the spasm of the brain vessels. Immunohistochemisty and Western blot were used to evaluate the expression of NLK at different time points in the basilar arterial wall. Results The pathological changeed including arterial narrowing, thickness of arterial wall, reductus of intima and hypertrophy of smooth muscle cells could be observed and such changes progressed with time and were more obvious on 3rd day. The cross-section area of BA on 3th day after SAH was about 43.5% of the control group＇s, and the wall thickness of BA was about 1.7 times of the control group＇s. The manifestation on 14th day was near to the control group. Western bol^analysis show that the expression of NLK decreased in SAH group, and reached to the bottom on 3rd day and 5th day, then increased. The level on 14th day was similar to the control group. Conclusions 1.The pathological changes including morphological changes,arterynarrowing, thickness of arterial wall suggest that CVS happens after SAH. 2. In SAH group, the expression of NLK in the BA walls has changes and been concerned with CVS. It suggests that NLK participates the pathological course of vasospasm.