Effects of Xiaotan Huayu Liqiao Formula on cognitive impairment in mice exposed to chronic intermittent hypoxia

doi:10.12047/j.cjap.5904.2020.032

Abstract

Abstract: Objective: To investigate the improvement effects of Xiaotan Huayu Liqiao Formula on cognitive impairment in mice exposed to chronic intermittent hypoxia (CIH), and to explore the related mechanisms. Methods: Forty-eight male C57 BL/6 mice were randomly divided into four groups as Normoxia, CIH, Formula+CIH and Formula group. Mice were exposed to normoxia in the normoxia and formula group, or intermittent hypoxia in CIH or Formula+CIH group (in the chambers, mice were filled with 100% N₂ to produce FiO₂ of 9% for 1. 5 min. The FiO₂ gradually returned to 21% over the remainder of each cycle. The exposure cycle was repeated every 3 min, 8 h/day for 35 days). Mice were treated with Xiaotan Huayu Liqiao Formula at the dose of 26. 8 g/kg by intragastric administration before CIH exposure. Meanwhile, mice in CIH and normoxia group were given the same volume of normal saline. When the experiment lasts for 26-35 d, Morris water maze was used to detect cognitive dysfunction in mice. At the end of 35 days, Y-maze was performed in each group. After anesthesia, hippocampus was isolated for morphological observation and Western blot ananlysis. Nissl staining and electron microscopy were adopted to assess the neuronal damage in hippocampus, and Western blot was used to detect the levels of PSD-95 and synapsin expression. Results: Compared with normoxia group,the performance of CIH mice was significantly reduced in Morris water maze and Y-maze(P＜0. 01,P＜0. 01). Both the number of Nissl staining positive cells and the thickness of the postsynaptic density in hippocampus were significantly reduced. And, the levels of PSD-95 expression in hippocampus was also decreased in the CIH group(P＜0. 01), however, no significant change of synapsin expression was observed. Compared to CIH group, administration of Xiaotan Huayu Liqiao Formula markedly improved performance of mice in Morris water maze and Y-maze (P＜0. 01), increased Nissl staining positive cells and the thickness of the postsynaptic density and PSD-95 expression in hippocampus (P＜0. 01). Conclusion: Xiaotan Huayu Liqiao Formula could alleviate the structural and functional impairment of the postsynaptic dense area, and improved CIH-induced cognitive dysfunction.

Key words: chronic intermittent hypoxia, cognitive impairment, hippocampus, PSD-95, Xiaotan Huayu Liqiao Formula, mice

CLC Number:

R259

ZHAO Yang, YANG Sheng-chang, YU Fu-yang, LI Wen-ya, JI En-sheng. Effects of Xiaotan Huayu Liqiao Formula on cognitive impairment in mice exposed to chronic intermittent hypoxia[J]. CJAP, 2020, 36(2): 143-147.

References

[1] Shen YC, Kung SC, Chang ET, et al.The impact of obesity in cognitive and memory dysfunction in obstructive sleep apnea syndrome[J]. Int J Obes(Lond), 2019, 43(2): 355-361.
[2] Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective[J]. Am J Respir Crit Care Med, 2002, 165(9): 1217-1239.
[3] Kerner NA, Roose SP. Obstructive sleep apnea is linked to depression and cognitive impairment: Evidence and potential mechanisms[J]. Am J Geriatr Psychiatry, 2016, 24(6): 496-508.
[4] Lal C, Strange C, Bachman D. Neurocognitive impairment in obstructive sleep apnea[J]. Chest, 2012, 141(6): 1601-1610.
[5] Li W, Yang S, Yu FY, et al.Hydrogen ameliorates chronic intermittent hypoxia-induced neurocognitive impairment via inhibiting oxidative stress[J]. Brain Res Bull, 2018, 143: 225-233.
[6] Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia--revisited--the bad ugly and good: implications to the heart and brain[J]. Sleep Med Rev, 2015, 20: 27-45.
[7] Gozal E, Row BW, Schurr A, et al.Developmental differences in cortical and hippocampal vulnerability to intermittent hypoxia in the rat[J]. Neurosci Lett, 2001, 305 (3): 197-201.
[8] Rao SK, Ross JM, Harrison FE, et al.Differential proteomic and behavioral effects of long-term voluntary exercise in wild-type and APP-overexpressing transgenics[J]. Neurobiol Dis, 2015, 78: 45-55.
[9] Ehrlich I, Malinow R. Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity[J]. J Neurosci, 2004, 24(4): 916-927.
[10]于富洋, 杨胜昌, 郭亚净, 等.消痰化瘀利窍方对慢性间歇性低氧暴露大鼠血压与心肌损伤的影响[J]. 郑州大学学报(医学版), 2019, 54(1): 29-32.
[11]Punjabi NM. The epidemiology of adult obstructive sleep apnea[J]. Proc Am Thorac Soc, 2008, 5(2): 136-143.
[12]Veasey SC. Piecing together phenotypes of brain injury and dysfunction in obstructive sleep apnea[J]. Front Neurol, 2012, 3(139): 1-9.
[13]Cai XH, Zhou YH, Zhang CX, et al.Chronic intermittent hypoxia exposure induces memory impairment in growing rats[J]. Acta Neurobiol Exp(Wars), 2010, 70(3): 279-287.
[14]王夏云, 杨关林. 再论“心主神志”与“脑主神志”[J]. 吉林中医药, 2009, 29(2): 100-102.
[15]曹慧娟, 郁志华, 陈久林. 轻度认知障碍的中医研究进展[J]. 世界科学技术—中医药现代化, 2015, 17(8): 1729-1733.
[16]Gozal D, Row BW, Gozal E, et al.Temporal aspects of spatial task performance during intermittent hypoxia in the rat: evidence for neurogenesis[J]. Eur J Neurosci, 2003, 18(8): 2335-2342.
[17]Calhoun ME, Jucker M, Martin LJ, et al.Comparative evaluation of synaptophysin-based methods for quantification of synapses[J]. J Neurocytol, 1996, 25(12): 821-828.
[18]Garner CC, Nash J, Huganir RL. PDZ domains in synapse assembly and signalling[J]. Trends Cell Biol, 2000, 10(7): 274-280.
[19]Chugh D, Nilsson P, Afjei SA, et al.Brain inflammation induces post-synaptic changes during early synapse formation in adult-born hippocampal neurons[J]. Exp Neurol, 2013, 250: 176-188.
[20]杨玉萍, 李瑞旻, 李佳佳, 等. 阻塞性睡眠呼吸暂停低通气综合征合并高血压中医分型与睡眠参数的相关性研究[J]. 江西中医药, 2018, 49(423): 38-41.