灵芝三萜对癫痫大鼠学习记忆损伤的效果

doi:10.3969/j.issn.1006-9771.2020.04.010

Abstract

Abstract:

Objective To study the effect of Ganoderma triterpenoids combined with exogenous monosialoteterahexosyl ganglioside (GM1) on cognitive dysfunction in rats with epilepsy.Methods A total of 75 Sprague-Dawley rats were divided randomly into blank control group, epileptic model group, Ganoderma triterpenoids group, GM1 group and GM1 combined with Ganoderma triterpenoids group (combination group), with 15 rats in each group. All the groups, except the blank control group, were intraperitoneally injected with pentylenetetrazol (PTZ) 35 mg/kg once a day for 28 days. Medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ. They were tested with Morris Water Maze; and were observed with transmission electron microscopy and HE staining for hippocampal neurons. Real-time quantitative polymerase chain reaction was used to detect the expression of actin-binding protein (Cofilin), synaptophysin (SYN) and growth-associated protein 43 (GAP-43) mRNA in hippocampus of rats.Results Compared with the blank control group, the escape lantency prolonged in the epileptic model group in all the time points (P < 0.05). Compared with the epileptic model group, the escape lantency shortened in the treatment groups somewhen ( P < 0.05). Compared with the epileptic model group, the number of crossing the platform increased in the treatment groups ( P < 0.01), and the time of staying in the target quadrant prolonged ( P < 0.01); while the number of pyramidal cells increased, the nuclear lysis and fragmentation reduced, the structure of neurons and the number of synapses improved, as well as the organelle structure. Compared with the blank control group, the expression of Cofilin mRNA increased ( P < 0.05), and the expression of SYN mRNA and GAP-43 mRNA decreased ( P < 0.05) in the epileptic model group; compared with the epileptic model group, the expression of Cofilin mRNA decreased ( P < 0.05), and the expression of SYN mRNA increased ( P < 0.05) in all the treatment groups, while the expression of GAP-43 mRNA increased ( P < 0.05) only in the combination group. Conclusion Ganoderma triterpenoids, GM1 and their combination can improve the learning and memory abilities of epileptic rats, which may be associated with increasing the expression of SYN and GAP-43, decreasing the expression of Cofilin, to promote the synaptic remodeling of hippocampal tissue and protect brain neurons from PTZ-induced epilepsy.

Key words: epilepsy, synaptic remodeling, synaptophysin, actin-binding protein, neuronal growth-associated protein 43, rats

CLC Number:

R742.1

NONG Xue-juan,JIN Jia-xi,ZHOU Bing-yu,ZHANG Li-feng,HONG Jian-wei,ZHAO Shuang. Effects of Ganoderma Triterpenoids on Learning and Memory Impairment in Rats with Epilepsy[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(4): 440-446.

Figures/Tables 6

References 25

[1]	Jette N, Fiest K M, Sauro K M, et al. Author response: prevalence and incidence of epilepsy a systematic review and meta-analysis of international studies[J]. Neurology, 2017, 89(6):641-642.
[2]	黄灵, 李雪斌, 黄建敏, 等. 癫痫致认知功能障碍的危险因素分析[J]. 右江医学, 2017, 45(4):400-402.
[3]	吴荣亮, 刘君星. 灵芝酸A对癫痫样放电海马神经元的影响[J]. 牡丹江医学院学报, 2015, 36(2):8-11.
[4]	宋保兰. 灵芝的药理作用研究进展[J]. 中国民族民间医药, 2014, 23(10):9-10.
[5]	栾倩, 刘蕾, 刘君星, 等. 灵芝酸对痫样放电海马神经元ERK1/2磷酸化水平的影响[J]. 黑龙江医药科学, 2014, 37(2): 1, 3.
[6]	娄玉霞. 单唾液酸神经节苷脂注射液在新生儿缺氧缺血性脑病治疗中的临床价值[J]. 现代预防医学, 2014, 41(4):635-637.
[7]	裴雪梅, 高然, 张文武, 等. 单唾液酸四己糖神经节苷脂对缺氧缺血性脑病患儿血清NSE、S-100B的影响[J]. 中国实用神经疾病杂志, 2015, 18(4):64-65.
[8]	Rong X, Zhou W, Chen X W, et al. Ganglioside GM1 reduces white matter damage in neonatal rats[J]. Acta Neurobiol Exp (Wars), 2013, 73(3):379-386.
[9]	Yue W, Liu Y X, Zang D L . Inhibitory effects of succnic acid on chemical kindling and amygdala electrical kindling in rats[J]. Acta Pharmacologica Sinica, 2002, 23(9):847-850.
[10]	赵爽, 邓佳卉, 徐志卿, 等. 癫痫与抑郁障碍共患关联机制的研究进展[J]. 中国康复理论与实践, 2016, 22(9):1036-1040.
[11]	Jennum P, Pickering L, Christensen J, et al. Morbidity and mortality of childhood- and adolescent-onset epilepsy: a controlled national study[J]. Epilepsy Behav, 2017, 66:80-85. doi: S1525-5050(16)30594-7 pmid: 28038391
[12]	张金波, 宋汉君, 刘爽, 等. 灵芝孢子粉对戊四氮活化海马神经细胞caspase-9表达的研究[J]. 现代生物医学进展, 2016, 16(10):1850-1853.
[13]	李晓敏, 肖锋, 靳玢玢, 等. 神经节苷脂GM1对Aβ_1-42诱导的AD小鼠学习记忆能力及神经细胞凋亡的影响[J]. 沈阳药科大学学报, 2019, 36(7):612-616.
[14]	吴荣亮, 刘君星. 灵芝酸A对癫痫样放电海马神经元的影响[J]. 牡丹江医学院学报, 2015, 36(2):8-11.
[15]	Ni Y F, Zhang W, Bao X F, et al. GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice[J]. Behav Pharmacol, 2016, 27(5):451-459. doi: 10.1097/FBP.0000000000000229
[16]	Wu G, Lu Z H, André S, et al. Functional interplay between ganglioside GM1 and cross-linking galectin-1 induces axon-like neuritogenesis via integrin-based signaling and TRPC5-dependent Ca²⁺ influx[J]. J Neurochem, 2016, 136(3):550-563. doi: 10.1111/jnc.2016.136.issue-3
[17]	赵爽, 蒋利和, 王居平, 等. 外源性神经节苷脂联合灵芝三萜化合物对癫痫脑损伤神经保护作用[J]. 现代预防医学, 2017, 44(4):701-705.
[18]	Zhong J Y, Magnusson K R, Swarts M E, et al. The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning[J]. Behav Neurosci, 2017, 131(6):470-482. doi: 10.1037/bne0000219
[19]	Jiang Y, Lu Y, Jia M, et al. Ketogenic diet attenuates spatial and item memory impairment in pentylenetetrazol-kindled rats[J]. Brain Res, 2016, 1646:451-458. doi: S0006-8993(16)30453-X pmid: 27343950
[20]	Kandimalla R, Manczak M, Fry D, et al. Reduced dynaminrelated protein 1 protects against phosphorylated Tau-induced mitochondrial dysfunction and synaptic damage in Alzheimer's disease[J]. Human Mol Genet, 2016, 25(22):4881-4897.
[21]	Brady M L, Pilli J, Lorenz-Guertin J M, et al. Depolarizing, inhibitory GABA type A receptor activity regulates GABAergic synapse plasticity via ERK and BDNF signaling[J]. Neuropharmacology, 2018, 128:324-339. doi: 10.1016/j.neuropharm.2017.10.022
[22]	张岩, 王海燕, 王影, 等. 左乙拉西坦对癫大鼠海马组织中SYN和GAP-43 mRNA表达的影响[J]. 临床儿科杂志, 2013, 31(7):670-673.
[23]	Shaw A E, Bamburg J R. Peptide regulation of cofilin activity in the CNS: a novel therapeutic approach for treatment of multiple neurological disorders[J]. Pharmacol Ther, 2017, 175:17-27. doi: 10.1016/j.pharmthera.2017.02.031
[24]	Noguchi J, Hayama T, Watanabe S, et al. State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines[J]. Sci Rep, 2016, 6:32897. doi: 10.1038/srep32897 pmid: 27595610
[25]	赵艳果, 王显鹤, 宋丽娜, 等. 法舒地尔对缺氧缺血性脑损伤新生大鼠脑组织中Cofilin、GAP-43表达的影响[J]. 黑龙江医药科学, 2018, 41(3):121-122, 124.

引物名称	引物序列
SYN	F: 5'-GAG TGT GCC AAC AAG ACG GAG AG-3'
SYN	R: 5'-ATT CAG CCG ACG AGG AGT AGT CC-3'
GAP-43	F: 5'-TAC CAC TGA TAA CTC GCC GTC CTC-3'
GAP-43	R: 5'-GTG ACA GCA GCA GGC ACA TCG-3'
Cofilin	F: 5'-AAG GAG AGC AAG AAG GAG GAC CTG-3'
Cofilin	R: 5'-GCA TCC TTG GAG CTG GCA TAG ATC-3'
GAPDH	F: 5'-GAC ATG CCG CCT GGA GAA AC-3'
GAPDH	R: 5'-AGC CCA GGA TGC CCT TTA GT-3'

组别	n	第1天	第2天	第3天	第4天	第5天
空白对照组	10	39.53±7.38	31.38±7.97	23.90±6.52	21.88±7.65	16.70±4.20
癫痫模型组	10	51.45±6.52^b	43.35±8.56^a	37.15±6.05^b	32.88±4.40^a	29.35±5.43^b
灵芝三萜组	10	50.83±5.01^b	37.53±15.65	30.15±10.79	25.85±12.48	21.88±10.68^c
GM1组	10	44.38±5.96^c	36.96±12.73	29.30±8.27^c	26.28±10.34	20.35±5.37^c
灵芝三萜联合GM1组	10	43.93±6.58^c,d	34.27±9.23	28.68±7.62^c	23.93±9.99^c	19.98±4.66^c
F值		6.337	1.574	3.511	1.946	5.216
P值		0.001	0.198	0.014	0.119	0.002

组别	n	穿越平台次数	目标象限停留时间(s)
空白对照组	10	6.4±0.84	40.75±2.55
癫痫模型组	10	3.1±1.37^a	26.78±3.32^a
灵芝三萜组	10	5.0±1.33^b	32.23±4.47^b
GM1组	10	4.9±0.99^b	33.42±5.37^b
灵芝三萜联合GM1组	10	5.7±0.95^b	35.25±4.82^b
F值		12.125	14.225
P值		< 0.001	< 0.001

组别	n	Cofilin	SYN	GAP-43
空白对照组	7	1.01±0.04	0.99±0.05	1.00±0.04
癫痫模型组	7	1.28±0.39^a	0.80±0.08^a	0.76±0.11^a
灵芝三萜组	7	1.02±0.10^b,c	0.95±0.21^b,c	0.77±0.11
GM1组	7	1.06±0.12^b,c	0.97±0.11^b,c	0.82±0.20
灵芝三萜联合GM1组	7	0.99±0.12^b,c	1.04±0.17^b,c	0.96±0.22^b,c
F值		3.780	7.223	3.058
P值		0.019	< 0.001	0.041

Effects of Ganoderma Triterpenoids on Learning and Memory Impairment in Rats with Epilepsy

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 6

References 25

Related Articles 15

Metrics

Comments

Recommended 0

[1]	LI Fang, HUO Su, DU Jubao, LIU Xiuzhen, LI Xiaoshuang, SONG Weiqun. Effect of transcranial direct current stimulation combined with task-oriented rehabilitation training on forelimb motor dysfunction in rats with spinal cord injury [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2023, 29(7): 777-781.
[2]	HUANG Zhilin, XU Fashao, SHI Jing, HUANG Gan, LIU Meifang, ZHANG Xiahui. Establishment of rat model of dysphagia after stroke by thread embolism [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2023, 29(10): 1147-1153.
[3]	QIN Yanqiang, DONG Hao, SUN Yingchun, CHENG Xiankuan, YAO Haijiang. Effects of different acupuncture schemes on neurotransmitters and related inflammatory factors in rats with post-stroke depression [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2023, 29(1): 30-37.
[4]	MIAO Pei,ZHANG Tong,MI Haixia,ZHANG Weidong. Learning and memory ability and its mechanism in rats with focal cerebral ischemia induced by two filament-occluded methods [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(7): 789-796.
[5]	ZHOU Xiaojue,FENG Jing,PANG Rizhao,LIU Jie,ZHANG Anren. Every-other-day fasting attenuated inflammation in rats after spinal cord injury via the aryl hydrocarbon receptor/suppressor of cytokine signaling 2/nuclear transcription factor-κB signaling pathway [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(5): 544-551.
[6]	SONG Shaofei,HOU Yuanyuan,WANG Yunlei,ZHANG Tong. Effects of circadian misalignment induced by abnormal photoperiod on expression rhythm of clock genes and glucose uptake related genes in gastrocnemius in rats [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(5): 552-558.
[7]	LI Tong,FANG Zhipeng,SHAO Yuping,WANG Ping. Effect of aerobic exercise on learning and memory, and synaptic plasticity of hippocampal neurons for sleep-deprived rats [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(11): 1270-1277.
[8]	Jing-yi WANG,Jie YIN,Jian-cheng LIU,Ri-zhao PANG,Wen-chun WANG. Effect of Iridoid-rich Fraction from Valeriana Jatamansi Jones on Neuron Pyroptosis in Rats with Acute Spinal Cord Injury [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(6): 653-660.
[9]	Wen-mei ZHOU,Tao TAO,Shuang WU,Ting-long WANG,Zheng-yi YANG,Ying ZHANG. Effects of Enriched Environment on Neurological Function and Glucose Metabolism in Ischemic Penumbra in Cerebral Ischemia-reperfusion Injury Rats [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(5): 522-529.
[10]	Qiong-fen WANG,Feng-bo WANG,Ke WANG,Yong-qiang ZHONG,Jiao-jiao WANG. Effect of Electroacupuncture at Fengchi on Astrocytes and Neurons in Rats with Acute Cerebral Infarction [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(3): 302-309.
[11]	Xiang-zhe LI,Jie DING,Qing-hua WANG,Chuan-ming DONG,Tong WANG,Qin-feng WU. Effects of Body Weight-supported Treadmill Training on Neuropathic Pain and Expression of Glutamate Decarboxylase (GAD)-65/67 in Spinal Dorsal Horn of Rats with Spinal Cord Injury [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(2): 131-136.
[12]	Kun AI,Ming XU,Qiong LIU,Shi-feng DENG,Ji-sheng LIU,Fang QI,Xi-qin YI,Qi-rui QU,Hong ZHANG. Effect of Electroacupuncture on Content of Cyclic Adenosine Monophosphate and Protein Kinase A, and Phosphorylation of Myosin Light Chain Kinase in Detrusor of Rats with Detrusor Hyperreflex after Suprasacral Spinal Cord Injury [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(2): 137-144.
[13]	LING Meng-yu,YANG Yi-zhuo,LIU Shuai,YE Chao-qun. Effect of Exercise on Expression of NeuN and SynapsinI in Cortex and Cognitive Function in Rats after Cerebral Ischemia-reperfusion [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(11): 1272-1281.
[14]	PENG Zhi-feng, ZHANG Yi-ping, ZHANG Ji-hong. Effect of Early Exercise Combined with Pentylenetetrazol on Neurologic Function after Cerebral Ischemia-reperfusion in Rats and Its Mechanism [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(1): 27-30.
[15]	CHEN Xiao-ping,WANG Ming-yang,MA Deng-lei,GONG Shi-li,ZHANG Li,LI Ya-li,LI Lin,HU Chao-ying,ZHANG Lan. Effects of Analgecine on Apoptosis and Neuroinflammation in Cerebral Ischemia-reperfusion Injury Rats [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(9): 1038-1044.