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醋酸盐和丙酸盐与间歇性 theta 爆发刺激作为治疗急性一氧化碳中毒大鼠迟发性脑病认知功能障碍和焦虑症状的新方法

Acetate and propionate vs. iTBS as a novel method for cognitive dysfunction and anxiety symptoms in delayed encephalopathy after acute carbon monoxide poisoning rat.

作者信息

Meng Tianyu, Zhang Xin, Zhao Jili, Xue Hui, Yu Lehua

机构信息

Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, China.

出版信息

Front Pharmacol. 2025 Feb 26;16:1520988. doi: 10.3389/fphar.2025.1520988. eCollection 2025.

Abstract

BACKGROUND

The optimal treatment methods for delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) were not identified. Thus, this study was conducted to compare the efficacies of intermittent theta burst stimulation (iTBS) and short-chain fatty acids (SCFAs) in treating cognitive dysfunction and anxiety symptoms of DEACMP rat.

METHODS

In phase I, a DEACMP rat model was built to assess the inflammation levels in the hippocampus and levels of SCFAs in the serum of DEACMP rats. In phase II, DEACMP rats were randomly assigned into four groups: DEACMP + placebo, DEACMP + SCFAs, DEACMP + sham iTBS, and DEACMP + iTBS. The intervention was continued for 2 weeks. A Morris water maze and open field tests were used to assess cognitive function and anxiety symptoms, respectively.

RESULTS

The levels of three inflammatory factors (IL-1β, IL-6, and TNF-α) and two SCFAs (acetate and propionate) were significantly increased and decreased, respectively, in DEACMP rats. After treatment, cognitive dysfunction and anxiety symptoms were significantly improved in the DEACMP + iTBS group and the DEACMP + SCFAs (consisting of acetate and propionate) group. Both SCFAs and iTBS could significantly improve the increased levels of IL-1β, IL-6, and TNF-α in the hippocampus, and SCFAs could also improve the decreased levels of GPR41, GPR43, dopamine, and norepinephrine in the hippocampus of DEACMP rats.

CONCLUSION

These results indicate that both iTBS and SCFA solutions consisting of acetate and propionate produced good effects on DEACMP rats by regulating inflammation levels in the hippocampus, and acetate/propionate-GPR41/GPR43-IL-1β/IL-6/TNF-α-dopamine/norepinephrine may be a potential pathway in SCFAs for the treatment of DEACMP.

摘要

背景

急性一氧化碳(CO)中毒后迟发性脑病(DEACMP)的最佳治疗方法尚未明确。因此,本研究旨在比较间歇性theta波爆发刺激(iTBS)和短链脂肪酸(SCFAs)对DEACMP大鼠认知功能障碍和焦虑症状的治疗效果。

方法

在第一阶段,建立DEACMP大鼠模型,以评估DEACMP大鼠海马中的炎症水平和血清中的SCFAs水平。在第二阶段,将DEACMP大鼠随机分为四组:DEACMP + 安慰剂组、DEACMP + SCFAs组、DEACMP + 假iTBS组和DEACMP + iTBS组。干预持续2周。分别采用Morris水迷宫和旷场试验评估认知功能和焦虑症状。

结果

DEACMP大鼠中三种炎症因子(IL-1β、IL-6和TNF-α)的水平显著升高,而两种SCFAs(乙酸盐和丙酸盐)的水平显著降低。治疗后,DEACMP + iTBS组和DEACMP + SCFAs(由乙酸盐和丙酸盐组成)组的认知功能障碍和焦虑症状均得到显著改善。SCFAs和iTBS均可显著改善DEACMP大鼠海马中IL-1β、IL-6和TNF-α升高的水平,且SCFAs还可改善DEACMP大鼠海马中GPR41、GPR43、多巴胺和去甲肾上腺素降低的水平。

结论

这些结果表明,iTBS以及由乙酸盐和丙酸盐组成的SCFA溶液均可通过调节海马中的炎症水平对DEACMP大鼠产生良好效果,且乙酸盐/丙酸盐-GPR41/GPR43-IL-1β/IL-6/TNF-α-多巴胺/去甲肾上腺素可能是SCFAs治疗DEACMP的潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ad/11897562/7b15ac94f4ae/fphar-16-1520988-g001.jpg

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