PDGFR信号对小鼠脑小血管病模型中血脑屏障损伤的研究

Improvement of blood-brain barrier injury by pdgfr signal in mouse cerebrovascular disease model

目的分析血小板衍生生长因子受体(PDGFR)信号对小鼠脑小血管病模型中血脑屏障损伤的研究。方法将PDGFR-β基因敲除小鼠和PDGFR-β基因未敲除小鼠均随机数字表法分为为KO假手术组、KO模型组、NKO假手术组和NKO模型组,每组各9只。模型组建立小鼠脑小血管病模型,假手术组除不进行慢性低灌注损伤外,其余操作与模型组一致。检测各组小鼠的认知能力、脑水肿、血脑屏障通透性、脑梗死体积、脑组织中PDGFR-β、α-平滑肌肌动蛋白(α-SMA)和层黏连蛋白(Laminin)的表达量、PDGFR-β、α-SMA、Laminin阳性面积、缺血边缘区的血管周细胞覆盖率和增殖率并进行比较。结果造模后,与两个假手术组相比,两个模型组小鼠的逃避潜伏期、同侧基底、对侧基底、同侧皮层以及对侧皮层含水量、EB+FITC-Dextran阳性细胞率表达量显著增加,穿越平台次数均显著减少(P<0.05),与NKO组相比,KO组小鼠研究指标变化趋势与上述一致(P<0.05)。与NKO模型组相比,KO模型组小鼠脑组织中PDGFR-β、α-SMA的表达量、脑缺血边缘、中心区PDGFR-β、α-SMA阳性面积、脑缺血边缘区周细胞覆盖率以及增殖率均显著降低,脑梗死体积和Laminin的表达量显著增加(P<0.05)。随着造模时间的延长,各组小鼠的逃避潜伏期、脑梗死体积均显著减少,穿越平台次数显著增加(P<0.05)。结论PDGFR信号对小鼠脑小血管病模型的血脑屏障损伤具有一定修复和改善作用,可增加缺血区血管周细胞的覆盖率和增值率,并降低血管通透性。

Objective To analyze the improvement of blood-brain barrier injury by pdgfr signal in mouse cerebrovascular disease model.Methods The PDGFR-B gene knockout mice and PDGFR-B gene unknockout mice were randomly divided into sham operation group and model group,with 9 mice in each group.Small cerebral vascular disease(CSVD)was established by bilateral carotid stenosis in the model group.The sham operation group does not undergo chronic hypoperfusion injury,and the other operations are the same as the model group.The cognitive ability,brain edema,permeability of blood-brain barrier,volume of cerebral infarction,expression of PDGFR-β,α-smooth muscle actin and laminin in brain tissue,positive area of PDGFR-β,positive area of α-SMA,vascular area of laminin,perivascular cell coverage rate and proliferation rate in the border area of blood deficiency were measured at the specified time after modeling.Results After modeling,compared with the two sham-operated groups,the escape latency,ipsilateral basal,contralateral basal,ipsilateral cortical and contralateral cortical water content,the expression of EB+FITC-Dextran positive cells increased significantly(P<0.05),the number of crossing platforms was significantly reduced(P<0.05);compared with the NKO model group,the expression levels of PDGFR-β and α-SMA,cerebral ischemic margin,PDGFR-β and α-SMA positive area in the central area,peripheral cell coverage and proliferation rate in the marginal zone of cerebral ischemia in the brain tissue of the KO model group were significantly reduced(P<0.05),the volume of cerebral infarction and the expression of Laminin increased significantly(P<0.05);with the extension of modeling time,the escape latency,cerebral infarction volume of mice in each group were significantly reduced,and the number of crossing platforms was significantly increased(P<0.05);PDGFR-β in brain tissue of KO model group was not expressed at different time points,while in NKO model group,it decreased significantly with the prolonged modeling time(P<0.05).Conclusion The PDGFR signal has a certain repair and improvement effect on the blood-brain barrier injury in the mouse cerebrovascular disease model,which can increase the coverage and value-added rate of perivascular cells in the ischemic area and reduce vascular permeability.