马尿酸 1 可改善慢性脑低灌注大鼠的认知功能下降，并改善其炎症和血脑屏障损伤。
Maresin 1 improves cognitive decline and ameliorates inflammation and blood-brain barrier damage in rats with chronic cerebral hypoperfusion.
机构信息
Department of Neurology, Zhongnan Hospital, Wuhan University, No.169, Donghu Road, Wuhan, Hubei 430071, China.
Department of Neurology, Zhongnan Hospital, Wuhan University, No.169, Donghu Road, Wuhan, Hubei 430071, China.
出版信息
Brain Res. 2022 Aug 1;1788:147936. doi: 10.1016/j.brainres.2022.147936. Epub 2022 May 6.
BACKGROUND
Chronic inflammation and blood-brain barrier destruction are interrelated pathological changes in chronic cerebral hypoperfusion (CCH) that promote vascular cognitive impairment (VCI). Therefore, we discussed the impact of the macrophage mediator in resolving inflammation 1 (Maresin 1) on the CCH-induced cognitive impairment and its underlying mechanisms.
METHODS
66 rats were randomly divided into three groups: Sham (n = 22), 2VO (n = 22), and 2VO + MaR1 (n = 22). Rats in three groups received 2-Vessel Occlusion (2VO) or sham operation and received intrathecal delivery of PBS or MaR1. Hippocampal blood flow and Modified neurological severity scores (mNSS) were used to confirm models' effect. Blood-brain barrier (BBB) damage was assessed by Evans blue (EB) leakage experiments and spectrophotometry, the BBB ultrastructure was observed with a transmission electron microscope (TEM), and the expression of zonula occluden-1 (ZO-1), claudin-5, and matrix metalloproteinases-9 (MMP-9) were detected with Enzyme-Linked Immunosorbent Assay (ELISA). Morris water maze (MWM) was used to assess cognitive function. Tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and nuclear factor-κB (NF-κB) expression were examined by Western blotting (WB) and ELISA. Immunofluorescence was used to detect microglia, astrocytes and oligodendrocytes.
RESULTS
Rats developed obvious cognitive impairment by CCH. BBB showed EB leakage, ultrastructural destruction, degradation of ZO-1, Claudin-5, and up-regulation of MMP-9. Inactivation of oligodendrocytes, activation of microglia and astrocyte and increased expression of NF-κB, TNF-α, and IL-1β has been detected. MaR1 administration significantly reverted these changes.
CONCLUSION
MaR1 can improve the CCH-induced cognitive impairment. Inflammatory resolution and BBB protection may be the mechanism of MaR1 to prevent CCH-induced cognitive impairment.
背景
慢性炎症和血脑屏障破坏是慢性脑低灌注（CCH）中的相关病理变化，促进血管性认知障碍（VCI）。因此，我们探讨了巨噬细胞介质消退因子 1（Maresin 1）对 CCH 引起的认知障碍的影响及其潜在机制。
方法
66 只大鼠随机分为三组：假手术组（Sham，n=22）、双侧颈总动脉结扎组（2VO，n=22）和 2VO+MaR1 组（n=22）。三组动物分别接受双侧颈总动脉结扎或假手术，并鞘内给予磷酸盐缓冲液（PBS）或 MaR1。用改良神经功能缺损评分（mNSS）和海马血流检测来确认模型效果。用伊文思蓝（EB）渗漏实验和分光光度法评估血脑屏障（BBB）损伤，用透射电子显微镜（TEM）观察 BBB 超微结构，用酶联免疫吸附试验（ELISA）检测紧密连接蛋白-1（ZO-1）、闭合蛋白-5（Claudin-5）和基质金属蛋白酶-9（MMP-9）的表达。用 Morris 水迷宫（MWM）评估认知功能。用 Western blot（WB）和 ELISA 检测肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）和核因子-κB（NF-κB）的表达。用免疫荧光法检测小胶质细胞、星形胶质细胞和少突胶质细胞。
结果
CCH 导致大鼠出现明显的认知障碍。BBB 出现 EB 渗漏、超微结构破坏、ZO-1、Claudin-5 降解和 MMP-9 上调。少突胶质细胞失活、小胶质细胞和星形胶质细胞激活，以及 NF-κB、TNF-α和 IL-1β表达增加。MaR1 给药可明显逆转这些变化。
结论
MaR1 可改善 CCH 引起的认知障碍。炎症消退和 BBB 保护可能是 MaR1 预防 CCH 引起的认知障碍的机制。
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