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目的研究米诺环素(MC)对脑缺血再灌注(I/R)大鼠血脑屏障损伤的影响,并探讨其可能的作用机制。方法采用Longa EZ法制备SD大鼠大脑中动脉栓塞(MCAO)模型。造模当天(第1天)ip给予MC 22.5和45 mg·kg-1,每天1次,连续7 d。分别于术后第2天和第7天采用横木行走试验评价各组动物运动功能;免疫组织化学法检测缺血侧脑血管周围免疫球蛋白IgG渗出、基质金属蛋白酶-9(MMP-9)以及一氧化氮合酶2(NOS2)的表达;Western blotting方法检测p-ERK1/2蛋白含量变化。结果术后第2天,I/R大鼠行走功能显著降低、脑组织IgG渗出显著增加、MMP-9和NOS2表达也明显增加(P<0.05);MC 45 mg·kg-1可明显改善I/R引起的IgG渗出及NOS2表达增加(P<0.05),MC 45与22.5 mg·kg-1均可明显抑制MMP-9的表达增加(P<0.05);各组p-ERK1/2表达无显著差异(P>0.05)。术后第7天,I/R大鼠行走功能评分仍显著低于假手术组,IgG渗出、MMP-9和NOS2表达依然维持在与术后第2天接近的高水平;MC 45与22.5 mg·kg-1可显著促进I/R大鼠行走功能的恢复、明显降低MMP-9和NOS2的表达(P<0.05);MCAO阴性对照组p-ERK1/2含量显著增加,MC各给药组均可显著抑制p-ERK1/2的增加(P<0.05)。结论 MC的脑保护作用与改善血脑屏障损伤有关,且可能与抑制MMP-9及NOS2表达相关,其可能通过抑制MAPK通路发挥作用。
Objective To investigate the effect of minocycline on blood-brain barrier injury in rats with cerebral ischemia-reperfusion (I / R) and to explore its possible mechanism. Methods The middle cerebral artery occlusion (MCAO) model of SD rats was established by Longa EZ method. On the day of modeling (day 1), ip was given to MC 22.5 and 45 mg · kg-1 once daily for 7 days. The motor function of each group was evaluated by walking on the second and seventh day after operation. Immunohistochemistry was used to detect the exudation of immunoglobulin IgG in the ischemic cerebrovascular and the expression of matrix metalloproteinase-9 (MMP-9) And nitric oxide synthase 2 (NOS2) expression; Western blotting method to detect p-ERK1 / 2 protein content. Results On the second day after operation, the walking function of I / R rats was significantly decreased, the exudation of IgG in brain tissue was significantly increased, and the expression of MMP-9 and NOS2 was also significantly increased (P <0.05); MC 45 mg · kg-1 I / R induced IgG exudation and increased expression of NOS2 (P <0.05), MC 45 and 22.5 mg · kg-1 significantly inhibited the expression of MMP-9 (P <0.05) There was no significant difference (P> 0.05). On the 7th day after operation, the walking function score of I / R rats was still significantly lower than that of the sham operation group and IgG exudation, while the expression of MMP-9 and NOS2 remained close to the high level at the 2nd day after operation. The MC 45 and 22.5 mg · kg-1 significantly promoted the recovery of walking function in I / R rats, and significantly reduced the expression of MMP-9 and NOS2 (P <0.05); the content of p-ERK1 / 2 in MCAO negative control group increased significantly Group can significantly inhibit the increase of p-ERK1 / 2 (P <0.05). Conclusion The protective effect of MC on brain injury is related to the improvement of blood-brain barrier injury, and may be related to the inhibition of the expression of MMP-9 and NOS2, which may play a role in the inhibition of MAPK pathway.