Jiao-tai-wan inhibits inflammation of the gut-brain-axis and attenuates cognitive impairment in insomnic rats
Jiao-tai-wan inhibits inflammation of the gut-brain-axis and attenuates cognitive impairment in insomnic rats
复制标题
交泰丸抑制肠脑轴炎症并减轻失眠大鼠的认知障碍
DOI：
10.1016/j.jep.2019.112478
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发表时间：
2020-03-25
影响因子：
5.4
通讯作者：
Dong, Hui
中科院分区：
文献类型：
--
作者：
Su, Hao;Zhang, Chu;Dong, Hui
民族药理学相关性：交泰丸是一种著名的传统中草药配方，用于治疗失眠和全身炎症。研究表明，慢性失眠可能导致认知障碍的流行。全身炎症和肠道通透性在神经退行性疾病进展中的作用备受关注。本研究目的：本研究旨在探讨胶泰丸是否具有促进肠上皮屏障修复的作用，以抑制睡眠剥夺（SD）大鼠的全身炎症和认知障碍。材料与方法：雄性肥胖抵抗SD大鼠部分睡眠剥夺16周。最后8周用胶胎丸治疗。采用Morris水迷宫测试其认知能力。使用酶联免疫吸附试验或聚合酶链反应测定脑脊液、组织或血清中的β 42和促炎细胞因子。采用异硫氰酸荧光素-葡聚糖灌流法检测小肠通透性，鲎试剂法检测血浆脂多糖（LPS）水平。结果：睡眠剥夺使大鼠Morris水迷宫成绩下降，脑内A β 42、caspase 3、IL-6和TNF-α水平升高。肠TLR 4/NF-κ B通路被激活，IL-6和TNF-α表达增加。肠组织中紧密连接蛋白的表达也减少。这增加了LPS、LPS结合蛋白、IL-6和TNF-α的肠通透性和循环。结论：交泰丸具有减轻部分睡眠剥夺大鼠全身炎症反应和认知功能障碍的作用。可能的潜在机制是通过阻止炎症触发通过肠-脑-轴转移。
Ethnopharmacological relevance: Jiao-tai-wan is a well-known traditional Chinese herbal medicine formula that is used to treat insomnia and systemic inflammation. Studies indicate chronic insomnia might contribute to the prevalence of cognitive impairment. The role of systemic inflammation and intestinal permeability in the progression of neurodegenerative diseases attracts much attention.Aim of the study: This study aimed to investigate if Jiao-tai-wan plays a role in promoting the repair of the intestinal epithelial barrier to suppress systemic inflammation and cognitive impairment in sleep-deprived (SD) rats.Materials and methods: Male obesity-resistant SD rats were partially sleep-deprived for 16 weeks. During the last 8 weeks, they were treated with Jiao-tai-wan. A Morris water maze was used to analyze their cognitive ability. A beta 42 and proinflammation cytokines in the cerebrospinal fluid, tissue, or serum were determined using enzyme-linked immunosorbent assay or polymerase chain reaction. Intestinal permeability was detected using the fluorescein isothiocyanate-dextran perfusion assay method, Plasma lipopolysaccharide (LPS) levels were detected with Tachypleus Amebocyte Lysate. Western bolt was used in the signaling pathway analysis.Results: Sleep deprivation deteriorated the performance of rats in the Morris water maze and increased the A beta 42, caspase3, IL-6, and TNF-alpha levels in their brains. The intestinal TLR4/NF-kappa B pathway was activated with an increase in the expression of IL-6 and TNF-alpha. The expression of tight junction proteins was also decreased in the intestinal tissue. This increased the intestinal permeability and circulation of LPS, LPS binding protein, IL-6, and TNF-alpha. Treatment with Jiao-tai-wan could partly reverse these changes.Conclusion: Jiao-tai-wan has the potential to attenuate systemic inflammation and cognitive impairment in partially sleep-deprived rats. The possible underlying mechanism is by preventing an inflammation trigger being transferred through the gut-brain-axis.