中文摘要：

目的探讨人类免疫缺陷病毒-1型反式转录激活因子（HIV-1 transactivator of transcription,HIV-1Tat）对血脑屏障（Blood-Brain Barrier,BBB）中紧密连接（tight junctions,TJs）Claudin-1、ZO-1和ZO-2蛋白表达的影响及17-β雌二醇（17-βestradiol,E2）对HIV-1 Tat诱导的紧密连接蛋白破坏的影响作用。方法同代人脑微血管内皮细胞（human brain endothelial cells,hCMEC/D3）分为培养基对照组（CTL组）给予无血清培养基处理;Tat＋E2组以浓度10-8mol/L E2预处理2 h后,再加入1μg/ml HIV-1 Tat共处理24 h;E2组给予10-8mol/L E2处理24 h;Tat组给予1μg/ml HIV-1 Tat处理24 h。采用蛋白免疫印迹（Western blot,WB）技术检测hCMEC/D3中Claudin-1,ZO-1和ZO-2蛋白表达。结果 HIV-1 Tat可诱导Claudin-1、ZO-1和ZO-2蛋白表达下调（分别P〈0.05,P〈0.01,P〈0.01）;E2可介导Claudin-1,ZO-1的蛋白表达上调（P〈0.01,P〈0.05）,然而对ZO-2蛋白表达无显著性差异（P〉0.05）;E2可抑制HIV-1 Tat诱导Claudin-1,ZO-2的蛋白表达下调（P〈0.05,P〈0.01）,但对ZO-1蛋白表达水平无显著性的差异（P〉0.05）。结论 HIV-1 Tat可诱导脑微血管内皮细胞间紧密连接Claudin-1,ZO-1和ZO-2的蛋白降解,破坏BBB完整性和通透性,而E2通过抑制HIV-1 Tat诱导紧密连接蛋白Claudin-1,ZO-2降解,对BBB起重要保护作用。

英文摘要：

Objective To investigate the effect of 17β-estradiol（ E2） on HIV-1 Tat- induced altertions of the tight junction protein expression. Methods Western blot was used to detected the expression of tight junction protein in human brain endothelial cells（ hCMEC / D3） treated with E2 and HIV-1 Tat. hCMEC / D3 were pretreated with serum free Endothelial Cell Basal Medium-2 was used as control（ CTL group）. The other groups included E2 ＋ Tat group（ cells treated with 10- 8mol / L E2 for 2h,then co-treated with HIV-1 Tat for 24h）,E2 group（ cells treated with estradiol for 24h） and Tat group（ cells treated with HIV-1 Tat for 24h）. Results The tight junction protein expression in hCMEC / D3 of Claudin-1, zona occludens-1（ ZO-1）,zona occludens-2（ ZO-2） decreased with treatment Tat for 24 h（ P 0. 05,P 0. 01,P 0. 01, respectively）. E2 induced upregulation of expression of Claudin-1,ZO-1（ P 0. 01,P 0. 05） and attenuated HIV-1 Tat-induced degrdation of Claudin-1 and ZO-2（ P 0. 05,P 0. 01）,however,the expression of ZO-1 was unaffected（ P 0. 05）. Conclusions HIV-1 Tat-induced the tight junction protein degrdation of Claudin-1,ZO-1,ZO-2 in human brain microvascular endothelial cells. Moreover,E2 can protecte against HIV-1 Tat-induced degradation of Claudin-1,ZO-2.