嘌呤能离子通道型受体7介导的帕金森大鼠认知功能障碍

燕洋洋; 郭凯; 孙志宏

doi:10.16098/j.issn.0529-1356.2023.05.005

PDF(1467 KB)

解剖学报 ›› 2023, Vol. 54 ›› Issue (5) : 531-537. DOI: 10.16098/j.issn.0529-1356.2023.05.005

神经生物学

嘌呤能离子通道型受体7介导的帕金森大鼠认知功能障碍

燕洋洋郭凯孙志宏*

作者信息 +

Purinergic ligand-gated ion channel 7 receptor-mediated cognitive impairment in Parkinson’s disease rats

YAN Yang-yang GUO Kai SUN Zhi-hong*

Author information +

文章历史 +

摘要

目的探讨嘌呤能离子通道型受体7（P2X7R）在帕金森（PD）大鼠认知功能障碍中的作用。方法成年大鼠90只实验分为5组，每组6只大鼠，3个重复，运用6-羟基多巴胺(6-OHDA)制备PD大鼠模型。向PD大鼠注射P2X7R激动剂2,3-腺苷5-三磷酸三乙铵盐（BzATP)和拮抗剂考马斯亮蓝G(CBBG)检测大鼠在水迷宫中的学习记忆能力和疼痛反应，Real-time PCR和Western blotting检测海马组织P2X7的表达情况。结果与正常大鼠相比，PD大鼠学习速度缓慢，记忆能力弱，CBBG提高了PD大鼠的学习记忆能力，BzATP使PD大鼠的学习记忆能力减退；海马组织Real-time PCR结果显示，与对照组相比，P2X7R在海马组织中mRNA表达量最高，CBBG组P2X7R表达量下调，BzATP组P2X7R表达量上调；对P2X7R进行Western blotting检测，与PD组相比，BzATP组P2X7蛋白表达量显著升高，CBBG组P2X7蛋白表达量较低。结论 PD大鼠存在认知功能障碍，CBBG可改善PD大鼠的学习记忆功能，BzATP可抑制PD大鼠的学习记忆功能。

Abstract

Objective To explore the role of purinergic ligand-gated ion chennel 7 receptor(P2X7R) in cognitive dysfunction in Parkinson’s disease rats. Methods Ninty rats was divided into 5 groups with 6 rats in each group with 3 repeats. The rat model of PD was established by 6-hydroxydopamine (6-OHDA). PD rats were injected with P2X7R agonists 2,3-adenosine 5-triethylammonium triphosphate (BzATP) and antagonists Comassie brilliant blue G (CBBG). The learning and memory ability and pain response of rats in the water maze were measured, and the expression of P2X7 in hippocampus was detected by Real-time PCR and Western blotting. Results Compared with the normal rats, PD rats had slow learning speed and weak memory ability. CBBG improved the learning and memory ability of PD rats, while BzATP decreased the learning and memory ability of PD rats. The result of Real-time PCR showed that compared with the control group, the expression of P2X7R mRNA was the highest in hippocampal tissue, the expression of P2X7R in CBBG group was down-regulated, and that of P2X7R in BzATP group was up-regulated. Compared with the PD group, Western blotting of P2X7R showed that the expression of P2X7 protein increased significantly in BzATP group, while the expression of P2X7 protein was lower in CBBG group. Conclusion Cognitive impairment exists in PD rats. CBBG can improve the learning and memory function of PD rats, and BzATP can inhibit the learning and memory function of PD rats.

导出引用

燕洋洋郭凯孙志宏. 嘌呤能离子通道型受体7介导的帕金森大鼠认知功能障碍[J]. 解剖学报. 2023, 54(5): 531-537 https://doi.org/10.16098/j.issn.0529-1356.2023.05.005

YAN Yang-yang GUO Kai SUN Zhi-hong. Purinergic ligand-gated ion channel 7 receptor-mediated cognitive impairment in Parkinson’s disease rats[J]. Acta Anatomica Sinica. 2023, 54(5): 531-537 https://doi.org/10.16098/j.issn.0529-1356.2023.05.005

中图分类号： R-332

参考文献

［1］Farlow J, Pankratz ND, Wojcieszek J, et al. Parkinson Disease Overview［J］. GeneReviewsTM. PubMed, 1993,(1):115-118.

［2］Guo K. Analysis of the expression of P2 family genes in rats and the role of P2X7 in mediating Parkinson’s disease ［D］. Shanxi Yan’an: Yan’an University, 2019. (in Chinese)

郭凯. 大鼠P2家族基因表达分析及P2X7介导帕金森病发生的作用研究［D］.陕西延安：延安大学, 2019.

［3］Spillantini MG, Crowther RA, Jakes R, et al. Alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies［J］. Proc Nat Acad Sci USA, 1998, 95:6469-6473.

［4］Blanchet PJ, Brefel-Courbon C. Chronic pain and pain processing in Parkinson’s disease［J］. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2018, 87(Pt B): 200-206.

［5］Shen YL, Wang XB, Feng LSh, et al. Effect of aerobic exercise on expression of P2X7 receptor in hippocampus and cerebral cortex of rats［J］. Chinese Journal of Sports Medicine, 2021, 40(12): 955-961. (in Chinese)

沈钰琳, 王雪冰, 冯连世, 等. 有氧运动对大鼠海马和大脑皮质P2X7受体表达的影响［J］. 中国运动医学杂志, 2021, 40(12):.955-961.

［6］Ralevic V, Burnstock G. Receptors for purines and pyrimidines［J］. Pharmacol Rev, 1998, 50(3):413-492.

［7］Guo K, Zou T, Zhang G, et al. Research progress of P2X7 receptor in pathological pain［J］. Journal of Yan’an University (Medical Science Edition), 2019, 17 (1): 86-88, 93. (in Chinese)

郭凯, 邹婷, 张鸽, 等. P2X7受体在病理性疼痛中的研究进展［J］. 延安大学学报(医学科学版), 2019, 17(1): 86-88, 93.

［8］Munoz Frances M, Gao R, Tian YZh, et al. Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice［J］. Sci Rep, 2017, 7(1):3539.

［9］Chu YX, Zhang Y, Zhang YQ, et al. Involvement of microglial P2X7 receptors and downstream signaling pathways in long-term potentiation of spinal nociceptive responses［J］. Brain Behav Immun, 2010, 24(7):1176-1189.

［10］Zhu JP, Zhong Q, Chen Ch, et al. Research progress on the role of P2X7 receptor in central nervous system［J］. Chinese Journal of Neuroimmunology and Neurology, 2018, 25(3): 208-211. (in Chinese)

朱进飘, 钟琦, 陈畅, 等. P2X7受体在中枢神经系统中的作用研究进展［J］. 中国神经免疫学和神经病学杂志, 2018, 25(3):208-211.

［11］Pasqualetto G, Brancale A, Young MT. The molecular determinants of small-molecule ligand binding at P2X receptors［J］. Front Pharmacol, 2018, 9: 58.

［12］Ren RR, Wang DM. Advances in the role of P2X7 receptors in neuropathic pain and morphine tolerance［J］. Journal of Neuroanatomy, 2020, 36(4): 459-463. (in Chinese)

任瑞瑞, 王冬梅. P2X7受体在神经病理性疼痛和吗啡耐受中的作用研究进展［J］. 神经解剖学杂志, 2020, 36(4): 459-463.

［13］Barone P, Aarsland D, Burn D, et al. Cognitive impairment in nondemented Parkinson’s disease.［J］. Movement Disorders, 2011, 26(14):2483-2495.

［14］Wang X, Ren J, Li J, et al. Mechanism of P2X7 receptor on cognitive impairment in rats with obstructive sleep apnea hypopnea syndrome［J］. South China Journal of National Defense Medicine, 2022, 536(3): 163-167. (in Chinese)

王新, 任娟, 李军, 等. P2X7受体对阻塞性睡眠呼吸暂停低通气综合征大鼠认知功能障碍的机制研究［J］. 华南国防医学杂志,2022, 36(3): 163-167.

［15］Yang YY. Changes of brain and hippocampal metabolism in Parkinson’s disease model induced by proteasome inhibitor and its relationship with memory impairment［D］. Hefei: Anhui Medical University, 2019. (in Chinese)

杨艳艳. 蛋白酶体抑制剂诱导帕金森病模型中脑、海马脑代谢的变化及其与记忆障碍的关系［D］. 合肥: 安徽医科大学, 2019.

［16］Yang YA, Shu Q, Chen L, et al. Effects of different anesthetic methods on ventricular catheterization in rats and their effects on survival rate［J］. Chinese Journal of Comparative Medicine, 2018, 28(6): 89-95. (in Chinese)

杨亚南, 舒晴, 陈丽, 等. 不同麻醉方法在大鼠脑室置管术中的效果及其对存活率的影响［J］. 中国比较医学杂志, 2018,28(6): 89-95.

［17］Niu ChSh, Yang YY. Double target injection of 6-OHDA to establish the rat model of Parkinson’s disease and improve the success rate［J］. Chinese Journal of Stereotactic and Functional Neurosurgery, 2008, (5): 257-262. (in Chinese)

牛朝诗, 杨艳艳. 双靶点注射6-OHDA建立帕金森病大鼠模型并提高成功率［J］. 立体定向和功能性神经外科杂志, 2008, (5):257-262.

［18］Sun ZhH, Xu YX, Guo K. Gender difference of pain behavior in rat model of Parkinson’s disease induced by 6-OHDA［J］. Chinese Journal of Pain Medicine, 2017, 23(11): 811-817. (in Chinese)

孙志宏, 徐雅皙, 郭凯. 6-OHDA致帕金森病大鼠模型疼痛行为学的性别差异［J］. 中国疼痛医学杂志, 2017, 23(11): 811-817.

［19］Huang LP, Deng MZh, Zhang QX. Self-made Xingnao defibrillator prescription has synergistic and antitoxic effect on Parkinson’s disease model rats induced by 6-hydroxydopa［J］. Journal of Liaoning University of Traditional Chinese Medicine, 2017,19(6): 45-47. (in Chinese)

黄丽平, 邓敏贞, 张芹欣. 自拟醒脑除颤方对6-羟基多巴诱导帕金森病模型大鼠增效减毒作用［J］. 辽宁中医药大学学报,2017, 19(6): 45-47.

［20］Ferrazoli EG, Souza HD, Nascimento IC, et al. Brilliant blue g, but not fenofibrate, treatment reverts hemiparkinsonian behavior and restores dopamine levels in an animal model of parkinson’s disease［J］. Cell Transplant, 2017, 26(4): 669-677.

［21］Zhou WSh, Wang J, Li QH, et al. Effect of Atto vastatin on the expression of A β and COX-2 in the brain of vascular dementia rats［J］. Medical Science Journal of Central South China, 2012, 40(4): 345-350. (in Chinese)

周文胜, 王佳, 李庆华, 等阿托伐他汀对血管性痴呆大鼠脑组织Aβ和COX-2表达的影响［J］. 中南医学科学杂志,2012, 40(4): 345-350.

［22］Okada A, Nakamura T, Suzuki J, et al. Impaired pain processing correlates with cognitive impairment in Parkinson’s disease［J］. Intern Med, 2016, 55(21): 3113-3118.

［23］Dong XW. Analysis of risk factors of cognitive impairment in Parkinson’s disease patients with pain［D］. Suzhou: Suzhou University, 2020.

董旭雯. 帕金森病伴疼痛患者发生认知功能障碍的相关危险因素分析［D］. 苏州:苏州大学, 2020.

［24］Zheng B, Ying YL, Zhang ShC, et al. Effect of purine receptor P2X7 inhibitor BBG on cognitive impairment in aged rats induced by isoflurane anesthesia［J］. Anatomical Research, 2016,38(3): 165-168.

郑彬, 应彦璐, 张顺才, 等. 嘌呤受体P2X7抑制剂BBG对异氟烷麻醉致老年大鼠认知功能障碍的影响［J］. 解剖学研究, 2016,38(3): 165-168. (in Chinese)

［25］Du XY, Zhou XM, Wan X, et al. Structure and function of P2X7 receptor in central nervous system［J］. Medical Review, 2012, 18(3): 330-332. (in Chinese)

杜侠莹, 周新妹, 万晓, 等. 中枢神经系统P2X7受体的结构与功能［J］. 医学综述, 2012, 18 (3): 330-332.

［26］Huang FR. P2X7R antagonist Brilliant Blue G studies the role of autophagy in MPTP-mediated Parkinson’s model ［D］. Jangsu Zhenjiang: Jiangsu University, 2020. (in Chinese)

黄斐然. P2X7R拮抗剂Brilliant Blue G通过调节自噬在MPTP介导的帕金森模型中的作用研究［D］. 江苏镇江：江苏大学, 2020.

［27］He YB, Taylor N, Fourgeaud L, et al. The role of microglial P2X7: modulation of cell death and cytokine release［J］. J Neuroinflammation, 2017, 14(1):135.

［28］Zhao Zh. A preliminary study on the activation of microglia mediated by P2Y (12) receptor and P2X7 receptor in neuropathic pain ［D］. Chongqing: Third Military Medical University, 2014. (in Chinese)

赵喆. P2Y(12)受体、P2X7受体介导小胶质细胞活化参与神经病理性疼痛的初步研究［D］. 重庆：第三军医大学, 2014.