己酮可可碱对脑小血管病模型大鼠神经血管单元保护作用的实验研究

Pentoxifylline protects neurovascular units in rats with CSVD

目的通过观察己酮可可碱对脑小血管病(CSVD)模型大鼠突触可塑性恢复以及神经血管单元的保护作用,探讨其治疗CSVD的可能病理机制。方法选取成年雄性SD大鼠36只随机分为对照组、模型组、药物组,每组12只。药物组腹腔注射己酮可可碱注射液100 mg/(kg·d)。通过Western Blot实验检测突触相关蛋白突触后致密蛋白95(PSD95)、突触素、血管内皮生长因子(VEGF)、神经元核抗原(NeuN)、胶质纤维酸性蛋白(GFAP)、紧密连接蛋白5(claudin5)蛋白表达。结果与对照组比较,模型组术后3、7 d逃避潜伏期明显延长,穿过平台次数、新物体识别指数、神经元树突棘密度、树突全长明显减少,脑组织VEGF、GFAP表达明显增加,NeuN、claudin5、PSD95、突触素表达明显减少(P<0.05,P<0.01)。与模型组比较,药物组大鼠术后3、7 d逃避潜伏期缩短[(16.85±3.36)s vs(28.06±2.43)s,P<0.05;(13.06±2.32)s vs(49.85±5.56)s,P<0.01],药物组术后穿过平台次数、新物体识别指数、神经元树突棘密度、树突全长、脑组织PSD95、突触素、VEGF、NeuN、GFAP、claudin5表达明显增加(P<0.05,P<0.01)。结论己酮可可碱能有效改善CSVD大鼠的神经功能,机制可能与其对神经血管单元的保护有关。

Objective To investigate the protective effect of pentoxifylline on synaptic plasticity and neurovascular units in rats with CSVD and investigated its pathological mechanism in the treatment of CSVD.Methods Thirty-six healthy adult male SD rats were randomly divided into control,model and drug groups(n=12).The rats from the drug group was treated by intraperitoneally injection of 100 mg/kg pentoxifylline every day.The expression of synapse related proteins PSD95,synaptophysin,VEGF,NeuN,GFAP and claudin5 was analyzed by Western blotting.Results Compared with the control group,the model group had significantly prolonged escape latency,reduced time of crossing the target platform,and lower new object recognition index and density and total length of dendritic spine,but enhanced expression of VEGF and GFAP in brain tissue,and decreased expression of NeuN,claudin5,PSD95 and synaptophysin in 3 and 7 d after modeling(P<0.05,P<0.01).Both pentoxifylline treatment for 3 and 7 d could shorten the escape latency[(16.85±3.36)s vs(28.06±2.43)s,P<0.05;(13.06±2.32)s vs(49.85±5.56)s,P<0.01],increase the number of crossing target platform,new object recognition index,density and total length of dendritic spine,and enhance the expression of PSD95,synaptophysin,VEGF,NeuN,GFAP and claudin5 when compared with the model group(P<0.05,P<0.01).Conclusion Pentoxifylline can effectively improve the neurological function of rat CSVD model,which may be associated with its protective action in the neurovascular unit.