[1]陈洁,赵松耀,李世泽,等.藏红花素通过调控cGMP/PKG通路对癫痫大鼠的神经保护及对海马神经元兴奋性的影响[J].卒中与神经疾病杂志,2022,29(04):349-354.[doi:10.3969/j.issn.1007-0478.2022.04.009]
　Chen Jie,Zhao Songyao,Li Shize,et al.The neuroprotection of crocin on the rats with epilepsy and its effect on the excitability of hippocampal neurons by regulating cGMP/PKG pathway[J].Stroke and Nervous Diseases,2022,29(04):349-354.[doi:10.3969/j.issn.1007-0478.2022.04.009]
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藏红花素通过调控cGMP/PKG通路对癫痫大鼠的神经保护及对海马神经元兴奋性的影响()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第29卷
期数:
2022年04期
页码:
349-354
栏目:
论著
出版日期:
2022-09-10

文章信息/Info

Title:
The neuroprotection of crocin on the rats with epilepsy and its effect on the excitability of hippocampal neurons by regulating cGMP/PKG pathway
文章编号:
1007-0478(2022)04-0349-06
作者:
陈洁; 赵松耀; 李世泽; 任仙
450000 郑州大学附属郑州中心医院神经内科(陈洁 赵松耀 李世泽); 郑州大学第一附属医院神经内科(任仙)
Author(s):
Chen Jie;  Zhao Songyao;  Li Shize;  et al.
Department of Neurology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou Henan 450000
关键词:
藏红花素; 环磷酸鸟苷; cGMP依赖性蛋白激酶; 癫痫; 神经元兴奋性
Keywords:
Crocin Cyclic guanosine phosphate cGMP-dependent protein kinase Epilepsy Neuronal excitability
分类号:
R743
DOI:
10.3969/j.issn.1007-0478.2022.04.009
文献标志码:
A
摘要:
目的 观察藏红花素对癫痫大鼠的神经保护及对海马神经元兴奋性的影响。方法 取45只大鼠,随机选取10只设为健康组,剩余35只建立癫痫模型,成功30只。随机分为癫痫组(10只)、藏红花素组(10只)、抑制剂组(10只); 藏红花素组腹腔注射藏红花素(50 mg/kg); 抑制剂组腹腔注射藏红花素(50 mg/kg),髓鞘注射ODQ[1H(1,2,4)oxadiazolo(4,3 α)quinoxaline 1 one] [环磷酸鸟苷(Cyclic guanosine monophosphate,cGMP)/cGMP依赖性蛋白激酶(cGMP-dependent protein kinase,PKG)通路抑制剂](10 μg/只); 健康组、癫痫组腹腔注射等体积生理盐水; 1次/d,干预14 d; 检测血清氧化应激反应水平指标; 检测神经元钙离子水平; 用原位末端标记法(Terminal deoxynucleoitidy transferase mediated nick end labeling,TUNEL)检测海马神经元凋亡率; 用免疫印迹法检测海马组织cGMP,PKG、磷酸化-PKG(Phosphorylation-PKG,p-PKG)蛋白表达水平。结果 与癫痫组比较,藏红花素组血清丙二醛(Malondialdehyde,MDA)水平、海马神经元内钙离子水平、海马神经元凋亡率降低,血清超氧化物歧化酶(Superoxide dismutase,SOD)活性水平、海马组织cGMP蛋白表达水平、p-PKG/PKG升高(P<0.05); 与藏红花素组比较,抑制剂组血清MDA水平、海马神经元内钙离子水平、海马神经元凋亡率升高,血清SOD活性水平、海马组织cGMP蛋白表达水平、p-PKG/PKG降低(P<0.05)。结论 藏红花素可抑制海马组织氧化应激,降低海马神经元兴奋性,保护神经功能,推测其作用机制可能与激活cGMP/PKG信号通路有关。
Abstract:
ObjectiveTo observe the neuroprotection of crocin on epileptic rats and its effect on the excitability of hippocampal neurons.Methods 45 rats were randomly divided into, healthy group(10 mice)and epilepsy model(35 mice). 30 rats of the epilepsy model group were successfully modeling, and the 31 mice were randomly divided into the epilepsy group(10 rats), the crocin treatment group(10 rats), and the crocin-inhibitor treatment group(10 rats). The crocin group was intraperitoneally injected with crocin(50 mg/kg). In the crocin-inhibitor group, crocin(50 mg/kg)was injected intraperitoneally, and ODQ(cyclic guanosine phosphate(cGMP)/cGMP-dependent protein kinase(PKG)pathway inhibitor)(10 μg each rat)was injected into the myelin sheath. The healthy group and the epilepsy group were intraperitoneally injected with an equal volume of normal saline(once/day for 14 days). Serum oxidative stress indicators, the neuronal calcium ion concentration was measured. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)was used to detect the apoptosis rate of hippocampal neurons. Western blotting was used to detect the expression of cGMP, PKG, and p-PKG in the hippocampus.Results Compared with the epilepsy group, serum malondialdehyde(MDA)level, calcium ion concentration in hippocampal neurons, the apoptosis rate of hippocampal neurons were decreasedin the crocin treatment group(P<0.05).Serum superoxide dismutase(SOD)activity level, hippocampal cGMP expression, and p-PKG/PKG were increased in the crocin group(P<0.05). Compared with the crocin group, serum MDA level, calcium ion concentration in hippocampal neurons, and the apoptosis rate of hippocampal neurons were increased; the serum SOD activity level, the hippocampal cGMP and p-PKG/PKG expression were decreased in the crocin-inhibitor treatment group(P<0.05).Conclusion Crocetin can inhibit oxidative stress in the hippocampus, reduce the excitability of hippocampal neurons, and protect nerve function. It is speculated that its mechanism is related to the activation of cGMP/PKG signaling pathway.

参考文献/References:

[1] Liu DH, Agbo E, Zhang SH, et al. Anticonvulsant and neuroprotective effects of paeonol in epileptic rats[J]. Neurochem Res, 2019, 44(11): 2556-2565.
[2] 马虹英,朱武,王灿,等.254例中国癫痫患者丙戊酸和2-丙基-4-戊烯酸浓度与不良反应的相关性[J].中南大学学报(医学版),2019,44(7):775-783.
[3] Moezifar M, Sayyah M, Zendehdel M, et al. Docosahexaenoic acid prevents resistance to antiepileptic drugs in two animal models of drug-resistant epilepsy[J]. Nutr Neurosci, 2019, 22(9): 616-624.
[4] Shahidani S, Rajaei Z, Alaei H. Pretreatment with crocin along with treadmill exercise ameliorates motor and memory deficits in hemiparkinsonian rats by anti-inflammatory and antioxidant mechanisms[J]. Metab Brain Dis, 2019, 34(2): 459-468.
[5] 都昇,宋君浩,刘丹琼,等.纳米金刚石对癫痫模型P65表达的影响[J].华中科技大学学报(医学版),2020,49(4):424-429.
[6] 李三宝,张伟.藏红花素对视网膜缺血再灌注损伤大鼠视网膜组织的保护作用[J].中国临床药理学杂志,2020,36(24):3999-4001.
[7] 张碧玉,颜学军,王军.脊髓NO/cGMP信号通路在右美托咪定减轻大鼠神经病理性痛中的作用[J].中华麻醉学杂志,2016,36(4):481-483.
[8] Li BG, Wu WJ, Zheng HC, et al. Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR-135a-5p to prevent the progression of epilepsy[J]. Kaohsiung J Med Sci, 2019, 35(9): 527-534.
[9] Wong M. The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex[J]. J Neurodev Disord, 2019, 11(1): 30.
[10] Wang R, An X, Zhao S. Effect of miR-124 on PI3K/Akt signal pathway in refractory epilepsy rats[J]. Cell Mol Biol(Noisy-le-grand), 2020, 66(2): 146-152.
[11] Forsberg M, Seth H, Björefeldt A, et al. Ionized Calcium in human cerebrospinal fluid and its influence on intrinsic and synaptic excitability of hippocampal pyramidal neurons in the rat[J]. J Neurochem, 2019, 149(4): 452-470.
[12] 孙宏,王小荣,陈松盛,等.定痫汤对癫痫大鼠海马PPARγ及神经保护作用[J].中华中医药杂志,2020,35(11):5769-5771.
[13] 赵永吉,陆莹,游志鹏.藏红花酸对链脲佐菌素诱导的糖尿病大鼠视网膜神经上皮的保护作用[J].中国药理学通报,2020,36(3):399-403.
[14] Mozaffari S, Ramezany YS, Motaghinejad M, et al. Crocin acting as a neuroprotective agent against methamphetamine-induced neurodegeneration via CREB-BDNF signaling pathway[J]. Iran J Pharm Res, 2019, 18(2): 745-758.
[15] Song Y, Li D, Farrelly O, et al. The mechanosensitive ion Channel piezo inhibits Axon regeneration[J]. Neuron, 2019, 102(2): 373-389.e6.
[16] Roy A, Groten J, Marigo V, et al. Identification of novel substrates for cGMP dependent protein kinase(PKG)through kinase activity profiling to understand its putative role in inherited retinal degeneration[J]. Int J Mol Sci, 2021, 22(3): 1180.
[17] Mohan S, Tiwari MN, Stanojevic' M, et al. Muscarinic regulation of the neuronal Na+/K+-ATPase in rat hippocampus[J]. J Physiol, 2021, 599(15): 3735-3754.

备注/Memo

备注/Memo:
基金项目:2019年河南省医学科技攻关计划项目(LHGJ20190081)
更新日期/Last Update: 2022-09-10