米诺环素对慢性脑缺血大鼠脑内Notch信号通路的影响

The effects of minocycline on Notch signaling in rat's brain with chronic cerebral hypoperfusion

目的观察慢性脑缺血后米诺环素是否可以通过调节Notch信号通路而发挥脑保护作用。方法将健康雄性SD大鼠40只随机分为5组(n=8):假手术(Sham)组、缺血模型(Model)组、DAPT组、米诺环素(Min)组、DAPT+米诺环素(DAPT+Min)组;双侧颈总动脉永久性结扎(2-VO)建立慢性脑缺血模型,给药1月后行为学检测大鼠的学习记忆能力,免疫组化和Western blot检测VEGF及Notch信号通路下游物质Hes1的表达水平。结果与假手术组比较,缺血模型组大鼠的学习记忆能力降低(P<0.05);米诺环素组与DAPT组比较,VEGF及Hes1的表达水平存在显著差异(P<0.01);米诺环素组分别于与缺血模型组和DAPT+米诺环素组比较,DAPT+米诺环素组与DAPT组比较,学习记忆能力、VEGF及Hes1的表达水平存在显著差异(P<0.05)。结论米诺环素可能通过对慢性脑缺血大鼠脑内Notch信号通路的调节来促进脑缺血后血管的新生,进而发挥脑保护作用。

Objective To observe whether minocycline could exert cerebral protective effect by regula- ting Notch signaling pathway after chronic cerebral ischemia. Methods Forty healthy male Sprague-Dawley rats were randomly divided into 5 groups （n = 8） ： Sham operation group, Ischemia model group, DAPT group, minocycline group, DAPT ＋ minocyeline group. The model of chronic cerebral ischemia was established by permanent bilateral common carotid artery ligation （2-VO）. After 1 month of administration, the learning and memory abilities of rats were tested by behavioral experiments. The expression levels ot＂ VEGF and Hesl, a downstream substance of Notch signaling pathway, were detected by immunohistochemistry and Western blot. Results Compared with sham operation group, the learning and memory abilities of the model group de- creased （P〈0. 05）. Compared with DAPT group, the expression levels of VEGF and Hesl were significantly different in minoeycline group （P〈0. （11）. Minoeyeline group were respectively compared with＂ the model group and the DAPT ＋ minocycline group, DAPT ＋ minocycline group was compared with DAPT group, their learning and memory abilities, VEGF and Hesl expression levels were significant differences（P〈0. 05）. Con- clusion Minocycline could promote angiogenesis by regulating Notch signaling pathway in the brain of chronic cerebral ischemia rats, and then exert neuroprotective effect.