抑制小凹蛋白减轻大鼠脑缺血/再灌注诱导的神经功能损伤

Inhibition of p-caveolin1 attenuates neurological injury induced by cerebral ischemia-reperfusion in rats

目的探讨小凹蛋白1(Cav1)的磷酸化在大鼠脑缺血/再灌注后神经功能损伤中的作用机制。方法将大鼠随机分为假手术组(sham)、模型组(model)和抑制剂组(PP2)。用改良神经功能缺损评分(mNSS)评价大鼠神经功能,氯化三苯基四氮唑(TTC)染色检测脑梗死体积,Nissl染色检测脑缺血/再灌注后组织形态,Tunel染色检测梗死灶周围细胞凋亡数量,Western blot和免疫荧光检测脑梗死周围组织中p-Cav1、胶质纤维酸性蛋白(GFAP)和离子钙结合接头分子1(Iba1)的表达。结果与假手术组相比,模型组大鼠mNSS评分增加(P<0.05);脑梗死体积明显增加(P<0.05),尼氏体数量减少(P<0.05);凋亡细胞数量增加(P<0.05);p-Cav1、GFAP和Iba1蛋白的表达量上调(P<0.05)。而抑制剂PP2能减轻上述指标的变化,保护脑缺血/再灌注损伤大鼠神经功能(P<0.05)。结论抑制p-Cav1可以改善大鼠脑缺血/再灌注后神经功能,其机制可能与抑制胶质细胞激活及相互作用有关。

Objective To explore the mechanism of phosphorylation of caveolin1(Cav1)in neurological injury after cerebral ischemia-reperfusion in rats.Methods The rats were randomly divided into sham group,model group and inhibitor group(PP2).Neurological function was evaluated by modified neurological deficit score(mNSS)neurobehavioral score,cerebral infarction volume was evaluated by triphenyltetrazolium chloride(TTC)staining,histomorphology after cerebral ischemia-reperfusion was evaluated by Nissl staining,and apoptosis of peri-infarcted tissue was detected by Tunel staining.Western blot and immunofluorescence were used to detect the protein expression of p-Cav1,glial fibrillary acidic protein(GFAP)and ion calcium binding junction molecule 1(Iba1)in the tissue around cerebral infarction.Results Compared with the sham operation group,there were significantly increased mNSS score,volume of cerebral infarction,number of apoptotic cells and expression of p-Cav1,GFAP and Iba1 in the model group,while the number of Nissl corpuscles decreased.The inhibitor PP2 reduced the changes of the above-mentioned indexes and protect the neurological function of rats with cerebral ischemia-reperfusion injury.Conclusions Inhibition of p-Cav1 may improve the neurological function after cerebral ischemia-reperfusion in rats with potential mechanism of inhibiting glial cell activation and interaction.