Astragalus injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice.
Astragalus injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice.
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黄芪注射液通过缓解小鼠急性神经炎症和 BBB 损伤以及上调 BDNF-CREB 通路改善脂多糖诱导的认知衰退
DOI：
10.1080/13880209.2022.2062005
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发表时间：
2022-12
影响因子：
3.8
通讯作者：
Feng, Shan
中科院分区：
文献类型：
--
作者：
Liu, Ke;Wan, Guoran;Jiang, Ruhong;Zou, Li;Wan, Dong;Zhu, Huifeng;Feng, Shan
摘要 背景 脓毒症后认知障碍是脓毒症幸存者的主要后遗症之一。黄芪注射液是临床上脓毒症的首选治疗方法。目的探讨黄芪注射液治疗脓毒症后认知障碍的疗效及相关机制。材料和方法 C57BL/6J 小鼠分为三组：对照组、LPS（2.5mg/kg，腹腔注射）和 LPS + 黄芪注射液（5.0mL/kg）。脓毒症存活小鼠连续注射黄芪注射液13天。首先进行行为测试来评估其好处。其次，在体内和体外评估炎症细胞因子的分泌、血脑屏障完整性、神经变性和蛋白质表达。结果 与LPS组相比，黄芪注射组小鼠在Morris水迷宫实验中逃避潜伏期较短（34.6秒对24.5秒）。黄芪注射液治疗可以逆转 LPS 诱导的小鼠和 BV2 细胞的神经炎症。连续注射黄芪治疗不仅可以预防血脑屏障功能障碍，还可以预防神经退行性变。进一步的分子对接测试和western blot结果表明，黄芪注射液的主要成分能够与TrkB相互作用（估计结合能为-7.0至-5.0kcal/mol），并上调小鼠慢性期BDNF/TrkB/CREB信号通路的蛋白表达。讨论 黄芪注射液治疗可以在 LPS 诱导的脓毒症期间减轻神经炎症、逆转 BBB 功能障碍、预防神经退行性变并上调 BDNF-CREB 通路，最终预防认知能力下降的发展。结论黄芪注射液可能是临床脓毒症幸存者的潜在预防和治疗策略。
Abstract Context Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. Astragalus injection is the normally preferred treatment in sepsis in clinical settings. Objective This study evaluated the benefits and related mechanism of Astragalus injection on post-sepsis cognitive impairment. Materials and methods C57BL/6J mice were divided into three groups: Control, LPS (2.5 mg/kg, i.p.), and LPS + Astragalus injection (5.0 mL/kg). The surviving mice from sepsis were injected with material named Astragalus injection continuously for 13 days. Behavioural tests were first conducted to evaluate the benefits. Second, inflammatory cytokines secretion, BBB integrity, neurodegeneration, and protein expression was evaluated in vivo and in vitro. Results Compared with the LPS group, mice in Astragalus injection group exhibited shorter escape latency (34.6 s versus 24.5 s) in the Morris water maze test. Treatment with Astragalus injection could reverse LPS-induced neuroinflammation in mice and BV2 cells. Continuous Astragalus injection treatment not only prevented blood–brain barrier dysfunction, but also prevented neurodegeneration. Further molecular docking tests and western blot results reflected that the main constituents of Astragalus injection could interact with TrkB (the estimated binding energy values were −7.0 to −5.0 kcal/mol) and upregulate the protein expression of BDNF/TrkB/CREB signalling pathway during the chronic stage in mice. Discussion Astragalus injection treatment could reduce neuroinflammation, reverse BBB dysfunction, prevent neurodegeneration, and upregulate BDNF-CREB pathway during LPS-induced sepsis, ultimately preventing the development of cognitive decline. Conclusion Astragalus injection could be a potential preventive and therapeutic strategy for sepsis survivors in clinical settings.
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影响因子：
14.8
作者：
Leger, Marianne;Quiedeville, Anne;Freret, Thomas
通讯作者：
Freret, Thomas
影响因子：
15.1
作者：
Reis, Patricia A.;Alexandre, Pedro C. B.;Bozza, Fernando A.
通讯作者：
Bozza, Fernando A.
影响因子：
3.5
作者：
Chi, J. M.;Mackay, M.;Sanelli, P. C.
通讯作者：
Sanelli, P. C.
梓醇对 RhoA/ROCK-2 通路的抑制和紧密连接蛋白的上调可抑制脂多糖诱导的血脑屏障通透性破坏
DOI：
10.3390/molecules23092371
发表时间：
2018-09-17
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Feng S;Zou L;Wang H;He R;Liu K;Zhu H
通讯作者：
Zhu H
影响因子：
3.1
作者：
Hoshino, Koji;Hayakawa, Mineji;Morimoto, Yuji
通讯作者：
Morimoto, Yuji