Department of Pharmacology, Guangxi Medical University, Nanning, Guangxi 530021, China.
Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Medical University, Nanning, Guangxi 530021, China.
Biomed Res Int. 2020 Feb 22;2020:2702175. doi: 10.1155/2020/2702175. eCollection 2020.
Chemokine CC motif ligand 2 (CCL2) is one of the most recognized proinflammatory chemokines, and the expression of CCL2 in the cerebrospinal fluid of patients infected with HIV-1 is significantly higher than that of healthy people. As such, it is seen as an important cause of HIV-associated neurocognitive disorder (HAND). Our previous investigation has confirmed the pathological role of CCL2 in mediating brain damage leading to cognitive dysfunction. Currently, however, research on therapeutic drugs for the central nervous system targeting CCL2 is very limited. Our present study used brain stereotactic technology to induce cognitive impairment in rats by injecting CCL2 (5 ng) into the bilateral hippocampus. To investigate the protective effect and mechanism of Tanshinone IIA (25, 50, 75 mg/kg/d) on CCL2-induced learning memory and cognitive impairment in rats, we performed the Morris water maze (MWM) and novel object recognition tests (NORT) on the rats. The results showed that Tanshinone IIA significantly alleviated CCL2-induced learning memory and cognitive dysfunction. Further studies on the hippocampal tissue of the rats revealed that Tanshinone IIA treatment significantly increased the activity of SOD and GSH-Px while the level of MDA decreased compared to the model group. Additionally, the relative expression of apoptosis-associated genes caspase-3, caspase-8, and caspase-9 and inflammation-associated genes IL-1 and IL-6 in Tanshinone IIA-treated rats was lower than that in model rats. Finally, we confirmed hippocampal neuron loss and apoptosis by Nissl staining and TdT-mediated dUTP Nick end labeling (TUNEL). Taken together, these data imply that Tanshinone IIA can ameliorate CCL2-induced learning memory and cognitive impairment by impacting oxidative stress, inflammation, and apoptosis. Tanshinone IIA may be a potential therapeutic agent for the treatment of HAND.
趋化因子 CC 基元配体 2（CCL2）是最受认可的促炎趋化因子之一，感染 HIV-1 的患者脑脊液中 CCL2 的表达明显高于健康人。因此，它被认为是 HIV 相关神经认知障碍（HAND）的重要原因。我们之前的研究证实了 CCL2 在介导导致认知功能障碍的脑损伤中的病理作用。然而，目前针对趋化因子 CCL2 的中枢神经系统治疗药物的研究非常有限。本研究采用脑立体定向技术，通过向双侧海马内注射 CCL2（5ng）诱导大鼠认知障碍。为了研究丹参酮 IIA（25、50、75mg/kg/d）对 CCL2 诱导的大鼠学习记忆和认知障碍的保护作用及其机制，我们对大鼠进行了 Morris 水迷宫（MWM）和新物体识别测试（NORT）。结果表明，丹参酮 IIA 能显著减轻 CCL2 诱导的学习记忆和认知功能障碍。进一步研究大鼠海马组织发现，与模型组相比，丹参酮 IIA 治疗可显著提高 SOD 和 GSH-Px 的活性，同时降低 MDA 水平。此外，丹参酮 IIA 治疗大鼠海马组织中凋亡相关基因 caspase-3、caspase-8 和 caspase-9 以及炎症相关基因 IL-1 和 IL-6 的相对表达水平均低于模型大鼠。最后，我们通过尼氏染色和 TdT 介导的 dUTP 缺口末端标记（TUNEL）证实了海马神经元的丢失和凋亡。综上所述，这些数据表明，丹参酮 IIA 通过影响氧化应激、炎症和细胞凋亡，可改善 CCL2 诱导的学习记忆和认知障碍。丹参酮 IIA 可能是治疗 HAND 的潜在治疗药物。
