* Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Yunnan Innovation Team of Standardization and Application Research in Tree Shrew, Kunming, Yunnan, P. R. China.
† School of Forensic Medicine, Kunming Medical University, Kunming, Yunnan, P. R. China.
Am J Chin Med. 2018;46(3):551-566. doi: 10.1142/S0192415X18500283.
Although antiretroviral therapy has helped to improve the lives of individuals infected with human immunodeficiency virus 1 (HIV-1), these patients are often still afflicted with HIV-1-associated neurocognitive disorders, which can lead to neurocognitive impairment and even dementia, and continue to hamper their quality of life. Methamphetamine abuse in HIV-1 patients poses a potential risk for HIV-associated neurocognitive disorders, because methamphetamine and HIV-1 proteins such as transactivator of transcription can synergistically damage the blood-brain barrier (BBB). In this study, we aimed to examine the effects of methamphetamine and HIV-1 Tat protein on the blood-brain barrier function and to determine whether ginsenoside Rb1 (GsRb1) plays a role in protecting the BBB. Sprague-Dawley rats were divided into four groups. The experimental groups received methamphetamine and HIV-1 Tat protein or both and the control group received saline or GsRb1 pretreatment. Oxidative stress-related factors, tight junction (TJ) proteins, blood-brain barrier permeability, and morphological changes were recorded in each group. The results showed that the group treated with Methamphetamine[Formula: see text]Tat showed a significant change at the ultrastructural level and in the levels of oxidative stress-related factors, TJ proteins, and BBB permeability, suggesting that the BBB function was severely damaged by HIV-1 Tat and methamphetamine synergistically. However, malondialdehyde levels and BBB permeability were lower and the oxidative stress-related factors superoxide dismutase and glutathione were higher in the GsRb1-treated group than in the Methamphetamine[Formula: see text]Tat-treated group, indicating that GsRb1 can protect the BBB against the toxic effects of HIV-1 Tat and methamphetamine. These results show that GsRb1 may offer a potential therapeutic option for patients with HIV-associated neurocognitive disorders or other neurodegenerative diseases.
尽管抗逆转录病毒疗法有助于改善感染人类免疫缺陷病毒 1（HIV-1）的个体的生活，但这些患者经常仍受到 HIV-1 相关神经认知障碍的困扰，这可能导致神经认知障碍甚至痴呆，并继续妨碍他们的生活质量。HIV-1 患者滥用冰毒会对 HIV 相关神经认知障碍构成潜在风险，因为冰毒和 HIV-1 蛋白如转录激活因子可以协同破坏血脑屏障（BBB）。在这项研究中，我们旨在研究冰毒和 HIV-1 Tat 蛋白对血脑屏障功能的影响，并确定人参皂苷 Rb1（GsRb1）是否在保护 BBB 方面发挥作用。Sprague-Dawley 大鼠分为四组。实验组接受冰毒和 HIV-1 Tat 蛋白或两者，对照组接受生理盐水或 GsRb1 预处理。记录每组的氧化应激相关因素、紧密连接（TJ）蛋白、血脑屏障通透性和形态变化。结果表明，Methamphetamine[Formula: see text]Tat 处理组在超微结构水平以及氧化应激相关因素、TJ 蛋白和 BBB 通透性水平上均发生了明显变化，提示 HIV-1 Tat 和冰毒协同作用严重损害了 BBB 功能。然而，与 Methamphetamine[Formula: see text]Tat 处理组相比，GsRb1 处理组的丙二醛水平和 BBB 通透性较低，氧化应激相关因素超氧化物歧化酶和谷胱甘肽较高，表明 GsRb1 可以保护 BBB 免受 HIV-1 Tat 和冰毒的毒性作用。这些结果表明，GsRb1 可能为 HIV 相关神经认知障碍或其他神经退行性疾病患者提供一种潜在的治疗选择。
