L-阿拉伯糖调节NF-κB通路对糖尿病并脑卒中大鼠血脑屏障的保护机制研究

Acute ischemic stroke is highly prevalence in China. Compare with the normal people, diabetic patients have higher stroke risk, severer condition and poorer prognosis, Therefore, It is urgency and necessary to study the prevention and treatment of stroke with diabetes mellitus in reality. Acute ischemic stroke causes blood brain barrier (BBB) damage, which further aggravate the progress of stroke. Diabetes not only change the morphology, barrier function and transfer function of BBB, but also change the physicchemical properties of brain micro-vessel. L-arabinose is a novel α-glucosidase inhibitor, obviously improves the level of fasting blood glucose, nevertheless, research on the protective effect and its mechanism in inhibiting NF-κB pathway and the protective effect with BBB after stroke is in deficiency. The research study the influence of diabetes on changes of BBB physiological functions and pathological change after cerebral ischemic stroke of rats, focusing on the protective effect with BBB and regulatory mechanism with NF-κB pathway of L-arabinose. This study will deepen the understanding of diabetes mellitus on BBB function and ischemic stroke pathophysiology process. Meanwhile, it also has great significance in guiding clinical treatment of diabetic patients with ischemic stroke.

急性缺血性脑卒中在我国的发病率极高。糖尿病者患发生脑卒中的几率大、病情重、预后差，因此，加强对糖尿病合并脑卒中防治的研究，有着现实的紧迫性及必要性。急性缺血性脑卒中引发血脑屏障损害,糖尿病不仅能改变血脑屏障形态学、屏障功能、转运功能，而且能改变大脑微血管理化性质，但血脑屏障病理生理及炎症因子转变的过程及机制尚不完全清楚。L-阿拉伯糖是一种新型α-糖苷酶抑制剂，能可明显改善空腹血糖，但尚缺乏其对卒中后抑制NF-κB通路及血脑屏障的保护作用和具体机制的研究。本课题研究糖尿病对血脑屏障的生理功能及缺血性脑卒中后大鼠病理变化的影响，重点探究L-阿拉伯糖调节NF-κB通路机制及血脑屏障的保护作用。本研究将加深糖尿病对缺血性脑卒中病理生理进程以及血脑屏障功能影响的了解，同时对糖尿病合并缺血性脑卒中临床治疗也具重要指导意义。

背景与目的：糖尿病患者发生缺血性中风后表现出比非糖尿病患者更为严重的神经功能缺损。 L-阿拉伯糖是一种α-葡萄糖苷酶抑制剂，可抑制餐后高血糖。已经显示出L-阿拉伯糖对代谢综合症具有保护作用，但是几乎没有报道描述L-阿拉伯糖在糖尿病加重的缺血性脑血管疾病中的神经保护作用。这项研究的目的是明确L-阿拉伯糖是否可以减轻糖尿病大鼠的脑缺血（CI）症状和保护血脑屏障（BBB）。.方法：我们在高脂饮食联合腹腔注射STZ体内制备的2型糖尿病（T2DM）大鼠模型中引入了大脑中动脉闭塞模型（MCAO），并给予L-阿拉伯糖进行处理。以研究是否L-阿拉伯糖可以减少脑梗死并发T2DM的梗死体积和恢复破坏的血脑屏障通透性，并改善内皮紧密连接蛋白的表达。.结果：在本研究中，我们发现糖尿病加重了神经系统损伤，增加了梗死体积，并加剧了MCAO中紧密连接蛋白降解所导致的BBB破坏，而L-阿拉伯糖缓解了以上糖尿病所导致的脑缺血损伤。L-阿拉伯糖降低了NF-κB和MAPK信号通路的激活，与非糖尿病大鼠相比，糖尿病大鼠MCAO中NF-κBp65，细胞间细胞粘附分子1（ICAM-1）的表达增加，胰高血糖素样肽-1（GLP-1）的表达减少。这些均可以被L-阿拉伯糖逆转。.结论：L-阿拉伯糖可通过下调NF-κB信号通路减轻糖尿病性脑缺血再灌注损伤后的BBB破坏，减轻糖尿病加重的脑缺血损伤。这些结果表明L-阿拉伯糖在糖尿病患者脑卒中血管保护中具有潜在的意义。