中文摘要：

目的探讨过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma,PPARγ）对人类免疫缺陷病毒-1型反式转录激活因子（HIV-1transactivator of transcription,HIV-1Tat）诱导的脑微血管内皮细胞中黏附分子反应的影响及其作用机制。方法将培养的人脑微血管内皮细胞（human cerebral microvascular endothelial cells,hCMEC/D3）给予HIV-1Tat、PPARγ激动剂罗格列酮、PPARγ拮抗剂GW9662、蛋白激酶B（Akt）抑制剂KP3721进行干预,并设立对照组。分别以蛋白免疫印迹法和实时反转录聚合酶链式反应检测hCMEC/D3中细胞间黏附分子-1（intercellular adhesion molecule-1,ICAM-1）、血管细胞黏附分子-1（vascular cell adhesion molecule-1,VCAM-1）蛋白和mRNA表达。结果 HIV-1Tat可诱导黏附分子ICAM-1和VCAM-1的蛋白（P〈0.05,P〈0.01）及其mRNA表达增加（均P〈0.01）,PPARγ激动剂罗格列酮可抑制HIV-1Tat诱导的ICAM-1蛋白（P〈0.05）与mRNA以及VCAM-1的mRNA表达（均P〈0.01）,而这种抑制作用可被PPARγ拮抗剂GW9662和Akt抑制剂KP3721逆转（均P〈0.01）。罗格列酮可抑制HIV-1Tat诱导的Akt磷酸化反应（P〈0.01）。结论 PPARγ可抑制HIV-1Tat诱导的脑微血管内皮细胞中黏附分子反应,Akt信号转导通路在PPARγ激动剂抑制血管内皮细胞炎性反应中起到重要的作用。

英文摘要：

Objective To evaluate the protection effect of peroxisome proliferator-activated receptor gamma （PPARy） against HIV-1 Tat-induced responses of adhesion molecules in brain microvascular endothelial cells and the possible signaling mechanism. Methods The protein expressions or mRNA levels of intercellular adhesion molecule-1 （ICAM-1） and vascular cell adhesion molecule-1 （VCAM-1） in human cerebral microvascular endothelial cells （hCMEC/D3） were assessed by Western blot or Real-time-PCR, with the exposure of HIV-1 Tat, rosiglitazone （PPARy agonist）, GW9662 （PPARy antagonist） and/or KP3721 （Akt inhibitor）. Results HIV 1 Tat induced upregulation of the protein expression of ICAM-1 （P〈0.05）, VCAM-1 （P〈0.01） in hCMEC/D3 as well as mRNA levels （P〈0.01, respectively）. Exposure to PPARy agonist rosiglitazone decreased Tat-induced protein expression of ICAM-1 （P〈0.05）, ICAM-1 mRNA and VCAM-1 mRNA levels （P〈0.01, respectively）. This inhibition was abolished by the addition of PPART antagonist GW9662 （ P〈0.01, respectively） and Akt inhibitor KP3721 （ P〈0.01, respectively）. Treatment of hCMEC/D3 with rosiglitazone dramatically inhibited the HIV-1 Tat-induced inflammatory activation of Akt phosphorylation （P〈0. 01）. Conclusions PPARγ may inhibit HIV-1 Tat-induced responses of adhesion molecules in brain microvascular endothelial cells. Akt signaling pathway plays a key role on the protection effect of PPARγ agonist on vascular inflammatory response that contributes to the destruction of blood brain barrier.