Effects of docosahexaenoic acid on locomotor activity in ethanol-treated HIV-1 transgenic rats.
Effects of docosahexaenoic acid on locomotor activity in ethanol-treated HIV-1 transgenic rats.
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DOI：
10.1007/s13365-017-0597-x
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发表时间：
2018-03
影响因子：
3.2
通讯作者：
Chang SL
中科院分区：
文献类型：
--
作者：
He J;Huang W;Zheng S;Vigorito M;Chang SL
酗酒影响人类免疫缺陷病毒（HIV）相关神经疾病的发病和进展。HIV - 1转基因（HIV - 1Tg）大鼠是用缺失gag和pol的HIV - 1病毒基因组构建的，以模拟接受联合抗逆转录病毒治疗（cART）的HIV感染患者。二十二碳六烯酸（DHA）是一种调节炎症反应的海洋化合物。本研究利用反复酗酒暴露于乙醇（EtOH）的HIV - 1Tg大鼠，检验DHA是否能够减轻EtOH和HIV蛋白对神经系统的有害影响。年轻成年雄性HIV - 1Tg和F344对照大鼠通过灌胃接受以下处理，持续5周（每组n = 6）：4 mL/kg/天的生理盐水作为对照（生理盐水组），20 mg/kg/天的DHA（DHA组），4.8 g/kg/天的52% w/v乙醇（乙醇组），或4.8 g/kg/天的52% w/v乙醇和20 mg/kg/天的DHA（DHA +乙醇组）。乙醇在每周的第5、6和7天给予。在每次处理前以及处理后45、90、135和180分钟，使用旷场试验评估运动活动（LMA）。反复酗酒暴露于乙醇逐渐降低了HIV - 1Tg和F344大鼠在每日处理前测量的LMA，这种效应仅在HIV - 1Tg大鼠中被DHA逆转。处理后且在乙醇影响下大鼠LMA的降低不太明显，并且DHA的逆转效应未达到统计学意义。HIV - 1Tg大鼠的血浆内毒素水平显著高于F344大鼠。HIV - 1Tg乙醇组纹状体中IL - 6和IL - 18的表达显著高于F344乙醇组。DHA显著降低了在HIV - 1Tg乙醇组中观察到的高水平的IL - 6、IL - 18和NF - κB表达。DHA似乎可改善炎症，从而减轻由乙醇和HIV - 1病毒蛋白共同作用导致的LMA降低。
Binge drinking affects the onset and progression of human immunodeficiency virus (HIV)-associated neurological disorders. The HIV-1 transgenic (HIV-1Tg) rat was created with a gag- and pol-deleted HIV-1 viral genome to mimic HIV-infected patients receiving combination anti-retroviral therapy (cART). Docosahexaenoic acid (DHA) is a marine compound that modulates inflammatory responses. Using HIV-1Tg rats subjected to binge exposure to ethanol (EtOH), this study examined whether DHA could reduce the detrimental neurological effects of EtOH and HIV proteins. Young adult male HIV-1Tg and F344 control rats received 4 mL/kg/day saline as a control (Saline group), 20 mg/kg/day DHA (DHA group), 4.8 g/kg/day 52% w/v EtOH (EtOH group), or 4.8 g/kg/day 52% w/v EtOH and 20 mg/kg/d DHA (DHA + EtOH group) by gavage for 5 weeks (n = 6 per group). EtOH was administrated on days 5, 6, and 7 of each week. Locomotor activity (LMA) was assessed using open field tests before and 45, 90, 135, and 180 min after each treatment. Repeated binge EtOH exposure gradually decreased LMA measured before daily treatments in HIV-1Tg and F344 rats, an effect that was reversed by DHA only in the HIV-1Tg rats. Decreased LMA of rats after treatment and under the influence of EtOH was less pronounced, and the reversal effect of DHA did not reach statistical significance. The plasma endotoxin level was significantly higher in HIV-1Tg rats than in F344 rats. IL-6 and IL-18 expression in the striatum was significantly higher in the HIV-1Tg EtOH group than in the F344 EtOH group. DHA significantly decreased the high levels of IL-6, IL-18, and NF-κB expression observed in the HIV-1Tg EtOH group. DHA appears to ameliorate inflammation and consequently lessen the reductions in LMA produced by the combination of EtOH and HIV-1 viral proteins.
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