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目的探讨Jagged1/Notch信号通路在糖尿病脑缺血再灌注损伤后病理性血管新生中的作用。方法选取40只雄性成年大鼠,取30只造模,诱导前禁食6 h,然后经腹腔注射链脉霉素溶液(streptozocin,STZ,60 mg/kg)。2周后采尾静脉血测定血糖,若空腹血糖>300 mg/dL视为Ⅰ型糖尿病(type 1 diabetes mellitus,T1DM)模型造模成功。并将其随机分为3组,分别为Ⅰ型糖尿病大鼠脑缺血脑缺血再灌注损伤组(T1DM-MCAo),Ⅰ型糖尿病大鼠脑缺血脑缺血再灌注损伤后Notch信号激活剂Jaggedl/FC蛋白干预组,Ⅰ型糖尿病大鼠脑缺血再灌注损伤后Notch拮抗剂γ-分泌酶抑制剂(DAPT)干预组,各组10只;另10只健康大鼠为对照组,4周后各组进行大脑中动脉缺血再灌注模型制备,分别在术后1天、7天、14天进行神经功能评价,并进行血脑屏障通透性评估。结果模型组EB含量均低于对照组,差异有统计学意义(P<0.05);Notch信号激活剂Jaggedl/FC蛋白干预组EB含量低于DAPT干预组、T1DM-MCAo组,DAPT干预组EB含量低于T1DM-MCAo组,差异有统计学意义(P<0.05)。结论通过对Jagged1/Notch信号通路进行调控,可较好的改善糖尿病脑缺血再灌注损伤后的血脑屏障通透性。
Objective To investigate the role of Jagged1 / Notch signaling pathway in pathological angiogenesis after diabetic cerebral ischemia-reperfusion injury. Methods Forty male adult rats were selected and 30 rabbits were fasted and fasted for 6 h before induction. Then streptozocin (STZ, 60 mg / kg) was injected intraperitoneally. After 2 weeks, the tail vein blood was taken to measure the blood glucose. If the fasting blood glucose> 300 mg / dL was regarded as type 1 diabetes mellitus (T1DM) model successfully. The rats were randomly divided into three groups: T1DM-MCAo group, diabetic rats with type 1 diabetes mellitus, Notch signaling activation after focal cerebral ischemia-reperfusion injury in type 1 diabetic rats Jaggedl / FC protein intervention group, type I diabetic rats after ischemia-reperfusion injury Notch antagonist γ-secretase inhibitor (DAPT) intervention group, 10 in each group; the other 10 healthy rats as the control group, After 4 weeks, the rats in each group were given the model of middle cerebral artery occlusion and reperfusion. The neurological function was evaluated on the 1st day, the 7th day and the 14th day after the operation, and the permeability of the blood-brain barrier was evaluated. Results EB contents in model group were lower than those in control group (P <0.05). EB content in Jaggedl / FC protein group was lower than that in DAPT group, while EB group in T1DM-MCAo group and DAPT group Lower than T1DM-MCAo group, the difference was statistically significant (P <0.05). Conclusion The regulation of Jagged1 / Notch signaling pathway can improve the permeability of blood-brain barrier after cerebral ischemia-reperfusion injury in diabetic rats.