新生隐球菌丝氨酸蛋白酶对脑微血管内皮细胞MMP-9、Tau—LRP、LDL—LRP的调控作用

目的:观察新生隐球菌分泌的丝氨酸蛋白酶对血脑屏障基质金属蛋白酶-9(MMP-9)、微管相关蛋白(Tau-LRP)和低密度脂蛋白受体相关蛋白(LDL-LRP)表达的影响以及抑肽酶的干预作用。方法:在含有成熟的脑微血管内皮细胞的培养皿中,分别加入丝氨酸蛋白酶相关成分及其特异性抑制剂后,应用免疫组织细胞化学技术检测MMP-9、Tau-LRP和LDL-LRP表达的变化。结果:应用新生隐球菌分泌的丝氨酸蛋白酶后内皮细胞的MMP-9、Tau-LRP、LDL-LRP的表达均升高,与对照组比较有显著统计学差异(P<0.01);抑制剂组的MMP-9、Tau-LRP和LDL-LRP与对照组比较无明显统计学差异(P>0.05)。结论:新生隐球菌分泌的丝氨酸蛋白酶通过上调MMP-9和(或)Tau-LRP、LDL-LRP表达,诱导内皮细胞基质降解和细胞自身微管结构及紧密连接发生变化,可能最终导致血脑屏障通透性增加。

Regulation effect of extracellular proteinase secreted by Cryptococcus neoformans on MMP-9,Tau-LRP,LDL-LRP of brain microvascular endothelial cell

Objective To study the influence of extracellular proteinase secreted by C.neoformans on the expressions of matrix metalloproteinase-9 (MMP-9), Tau-LRP and LDL-LRP as well as the effect of aprotinin. Methods Extracellular proteinase and treated specific inhibitor were added into mature brain microvascular endothelial cells, respectively. The expression of MMP-9, Tau-LRP and LDL-LRP were measured with immunohistochemical method. Results The expression of MMP-9 and/or Tau-LRP , LDL-LRP were markedly increased compared with control group(P < 0.01). In inhibitor group, the morphology and MMP-9 or Tau-LRP or LDL-LRP expression of cells had no significant difference compared with control group(P > 0.05). Conclusion Extracellular proteinase secreted by natural C.neoformans may up-regulate MMP-9 and/or Tau-LRP,LDL-LRP expression, induce BMEC degradation and/or change micro-tubular structure and tight junction of itself, possible increase BBB permeability at the final.