慢性缺血性脑白质脱髓鞘比格犬模型中Tau蛋白表达及可能原因

Tau protein expression and possible reasons in Beagle dog model of chronic ischemic cerebral white matter dysmyelination

目的探讨慢性缺血性脑白质脱髓鞘比格犬模型中Tau蛋白表达水平变化及可能原因。方法将16只成年比格犬按照完全随机数字表法分为A组(假手术组)及B、C、D组(观察组),每组各4只,应用四血管结扎法制作不同程度脑缺血动物模型。选取双侧侧脑室边缘部位脑白质,用神经胶质抗原2(NG2)标记少突胶质前体细胞(OPCs)、2,3-环核苷3-磷酸二酯酶(CNPase)标记成熟少突胶质细胞(OLs),采用免疫组织化学法检测Tau、NG2、CNPase,以平均光密度值量化表达水平。采用Pearson直线相关分析法分析Tau、NG2、CNPase之间的相关性。结果苏木精-伊红(HE)染色可见慢性脑缺血后脑白质明显脱髓鞘改变,A、B、C、D组LFB染色后评分分别为(0.75±0.71)、(1.38±0.06)、(1.63±0.52)、(1.88±0.64)分,与A组比较,B、C、D组评分更高(P<0.05)。与A组比较,B、C、D组Tau蛋白及NG2表达水平明显增高(P<0.05);CNPase表达水平明显降低(P<0.05)。Pearson线性相关分析显示Tau与NG2的表达水平呈正相关(r=0.277,P=0.006);Tau、NG2与CNPase的表达水平呈负相关(r=-0.303、-0.402,P=0.003、0.001)。结论 Tau蛋白在慢性缺血性脑白质脱髓鞘比格犬模型中的表达增加可能与OPCs分化成熟障碍相关。

Objective To explore the expression level and possible reasons of Tau protein in Beagle dog model of ischemic cerebral white matter（WM） demylination. Methods Sixteen adult Beagle dogs were divided into the sham operation group（A） and observation group B,C and D according to the completely random mumber table method,4 cases in each group. Different degrees of cerebral ischemia animal models were established by 4-vessel occlusion（4-VO） method. The bilateral ventricle edge white matter （WM） was selected. The oligodendrocyte precursors（OPCs） were labeled by NG2. The mature oligodendrocytes（Ols） were labeled by CNPase. Tau, NG2 and CNPase were detected by using the immunohistochemical method. The expression level was quantified by the mean optical value. The correlation among Tau,NG2 and CNGase was analyzed by adopting the Pearson linear correlation analy- sis. Results The HE staining showed obvious changes of WM demylination after chronic cerebral ischemic. The scores after LFB staining in the group A,B,C and D were（0. 755=0. 71） points, （1.38-4-0.06） points, （t. 63q-0.52） points and（1.88-4-0. 64） points. Compared with the group A,the scores in the group B,C and D were much higher（P^0.05）. Compared with the group A, the expression levels of Tau protein and NG2 were significantly increased（P^0.05）, while the CNPase expression level was signifi- cantly decreased（P^0.05）. The Pearson correlation analysis showed that Tau expression level was positively correlated with the NG2 expression level（r= 0. 277 ,P=0. 006） Tau and NG2 were negatively correlated With the CNPase level（r=--0. 303,--0. 402, P= 0. 003,0. 001）. Conclusion The increase of Tau expression in Beagle dog model of ischemic cerebral WM demylination may be related to the differentiation dysmaturity of OPCs.