本文選題：HIV- + Tat　； 參考：《中風(fēng)與神經(jīng)疾病雜志》2017年02期

【摘要】：目的探討Ras信號(hào)傳導(dǎo)通路在人類免疫缺陷病毒-1型反式轉(zhuǎn)錄激活因子(HIV-1 transactivator of transcription,HIV-1 Tat)誘導(dǎo)血腦屏障(BBB)中緊密連接蛋白Zonula Occludens(ZO)-1及腦啡肽酶(Neprilysin,NEP)破壞的作用。方法以不同濃度Ras信號(hào)傳導(dǎo)通路抑制劑法尼基硫代水楊酸(farnesylthiosalicylic acid,FTS)刺激培養(yǎng)好的人腦微血管內(nèi)皮細(xì)胞(human cerebral microvascular endothelium cells,HBEC-5i),并設(shè)立對照組,觀察其對細(xì)胞活力的影響。分別予以HIV-1 Tat、FTS刺激細(xì)胞,以蛋白免疫印跡法及實(shí)時(shí)反轉(zhuǎn)錄聚合酶鏈?zhǔn)椒磻?yīng)(realtime reverse transcription polymerase chain reaction,RT-PCR)檢測HIV-1 Tat誘導(dǎo)的緊密連接蛋白ZO-1及NEP(腦內(nèi)降解β淀粉樣蛋白Amyloid-beta,Aβ的限速酶)的蛋白和mRNA表達(dá)的變化。結(jié)果 FTS在20μmol/L(0.35±0.06)以下時(shí)對HBEC-5i活力無明顯影響(P0.05),HIV-1 Tat能抑制HBEC-5i的ZO-1、NEP蛋白(0.53±0.07,P0.01;0.40±0.04,P0.05)與mRNA(0.42±0.10,P0.05;0.31±0.09,P0.05)的表達(dá)。用FTS阻斷Ras信號(hào)通路后可顯著增加ZO-1、NEP蛋白(1.20±0.22,P0.01;0.58±0.03,P0.05)及mRNA(1.10±0.19,P0.05;0.97±0.38,P0.05)的表達(dá)。結(jié)論 HIV-1 Tat可促進(jìn)緊密連接蛋白ZO-1蛋白和mRNA下調(diào)而導(dǎo)致血腦屏障破壞,同時(shí)誘導(dǎo)腦內(nèi)腦啡肽酶NEP蛋白和mRNA下調(diào),可能導(dǎo)致Aβ在腦內(nèi)沉積增加。阻斷Ras信號(hào)傳導(dǎo)通路可抑制HIV-1 Tat誘導(dǎo)的ZO-1和NEP破壞,可能減少Aβ在腦內(nèi)的沉積。
[Abstract]:Objective to investigate the effect of Ras signal transduction pathway on the destruction of tight junction proteins Zonula Occludens (ZO) -1 and neprilysin nep (NEP) in blood brain barrier (BBB) induced by HIV-1 transactivator of transcriptional activator (HIV-1 tat). Methods the cultured human microvascular endothelial cells (human cerebral microvascular endothelium cells) were stimulated with different concentrations of Ras signal transduction pathway inhibitor farnesylthiosalicylic acidosalicylic acid (farnesylthiosalicylic acidosalicylic acid) and the control group was set up to observe its effect on cell viability. The cells were stimulated by HIV-1 Taton FTS. The protein and mRNA expression of tight junction protein ZO-1 and nep (rate-limiting enzyme for degradation of amyloid beta A 尾) induced by HIV-1 tat were detected by Western blot and real-time reverse transcription polymerase chain reaction (RT-PCR). Results when the concentration of FTS was below 20 渭 mol / L (0.35 鹵0.06), there was no significant effect on the activity of HBEC-5i (P0.05). HIV-1 tat could inhibit the expression of ZO-1NEP protein (0.53 鹵0.07) and mRNA (0.42 鹵0.10P0.05N) and mRNA (0.42 鹵0.10P0.05P, 0.31 鹵0.09p0.05) of HBEC-5i. After blocking the Ras signal pathway with FTS, the expression of ZO-1Nep protein (1.20 鹵0.22P0.01U 0.58 鹵0.03p0.05) and mRNA (1.10 鹵0.19P0.0550.97 鹵0.38p0.05) were significantly increased. Conclusion HIV-1 tat can promote the down-regulation of tight junction protein ZO-1 protein and mRNA leading to the breakdown of blood-brain barrier, and induce the down-regulation of NEP protein and mRNA in the brain, which may lead to the increase of A 尾 deposition in the brain. Blocking the Ras signaling pathway can inhibit the destruction of ZO-1 and NEP induced by HIV-1 tat, and may reduce the deposition of A 尾 in the brain.
【作者單位】： 廣西醫(yī)科大學(xué)第一附屬醫(yī)院神經(jīng)內(nèi)科;廣西廣西壯族自治區(qū)南溪山醫(yī)院神經(jīng)內(nèi)科;
【基金】：國家自然科學(xué)基金(No.81371333)
【分類號(hào)】：R512.91;R747.9

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