MiR-139-5p靶向RIPK1/RIPK3/MLKL信号通路对慢性脑低灌注大鼠认知障碍的影响

doi:10.11958/20230110

天津医药 ›› 2023, Vol. 51 ›› Issue (11): 1187-1192.doi: 10.11958/20230110

MiR-139-5p靶向RIPK1/RIPK3/MLKL信号通路对慢性脑低灌注大鼠认知障碍的影响

史文倩(), 赵美英, 黄捷, 贺桂, 汪桂青^△()

郑州大学附属郑州中心医院老年医学科（邮编450000）

收稿日期:2023-02-01 修回日期:2023-03-29 出版日期:2023-11-15 发布日期:2023-11-07
通讯作者: ^△E-mail：b0517012200@126.com
作者简介:史文倩（1987），女，主治医师，主要从事认知障碍方面研究。E-mail：wenqianwork@163.com
基金资助:
河南省医学科技攻关计划联合共建项目(LHGJ20210767)

Influence of miR-139-5p on cognitive dysfunction in rats with chronic cerebral hypoperfusion by targeting RIPK1/RIPK3/MLKL signal pathway

SHI Wenqian(), ZHAO Meiying, HUANG Jie, HE Gui, WANG Guiqing^△()

Department of Geriatrics, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, China

Received:2023-02-01 Revised:2023-03-29 Published:2023-11-15 Online:2023-11-07
Contact: ^△E-mail：b0517012200@126.com

史文倩, 赵美英, 黄捷, 贺桂, 汪桂青. MiR-139-5p靶向RIPK1/RIPK3/MLKL信号通路对慢性脑低灌注大鼠认知障碍的影响[J]. 天津医药, 2023, 51(11): 1187-1192.

SHI Wenqian, ZHAO Meiying, HUANG Jie, HE Gui, WANG Guiqing. Influence of miR-139-5p on cognitive dysfunction in rats with chronic cerebral hypoperfusion by targeting RIPK1/RIPK3/MLKL signal pathway[J]. Tianjin Medical Journal, 2023, 51(11): 1187-1192.

摘要/Abstract

摘要：

目的探究微小RNA（miR）-139-5p靶向受体相互作用蛋白激酶（RIPK）1/RIPK3/混合系列蛋白激酶结构域蛋白（MLKL）信号通路对慢性脑低灌注（CCH）大鼠认知障碍的影响。方法将60只SPF级SD大鼠采用随机数字表法分为假手术组（Sham组）、模型组（Model组）、miR-NC组、miR-139-5p mimic组、miR-139-5p mimic+RIPK1抑制剂Nec-1组（miR-139-5p mimic+Nec-1组），每组12只。除Sham组外，其余组均采用永久性结扎双侧颈总动脉构建CCH模型。采用新物体识别实验、Morris水迷宫实验评价大鼠的认知功能；酶联免疫吸附试验（ELISA）检测大鼠海马组织谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）、丙二醛（MDA）、肿瘤坏死因子（TNF）-α、白细胞介素6（IL-6）水平。实时荧光定量PCR（qPCR）法检测大鼠海马组织miR-139-5p及RIPK1、RIPK3、MLKL mRNA表达。Western blot法检测大鼠海马组织RIPK1、RIPK3、MLKL、突触素（SYP）、突触后密度蛋白95（PSD95）、α-突触核蛋白（α-SYN）蛋白的表达。双萤光素酶报告基因实验验证miR-139-5p和RIPK1的靶向关系。结果与Sham组相比，Model组大鼠分辨系数降低，目标象限停留时间缩短，海马组织miR-139-5p、GSH-Px、SOD水平降低，SYP、PSD95蛋白表达降低（P<0.05），逃避潜伏期延长，海马组织MDA、TNF-α、IL-6水平升高，RIPK1、RIPK3、MLKL mRNA和蛋白、α-SYN蛋白表达升高（P<0.05）。与Model组、miR-NC组相比，miR-139-5p mimic组相关指标的表达趋势与上述相反（P<0.05）。Nec-1进一步促进了上调miR-139-5p表达对CCH大鼠认知功能的恢复（P<0.05）。miR-139-5p和RIPK1存在结合位点。结论上调miR-139-5p可能通过靶向抑制RIPK1/RIPK3/MLKL信号通路减轻CCH大鼠的认知障碍。

关键词: 认知障碍, RIPK1/RIPK3/MLKL信号通路, 微小RNA-139-5p, 慢性脑低灌注

Abstract:

Objective To investigate the influence of miR-139-5p on cognitive dysfunction in chronic cerebral hypoperfusion (CCH) rats by targeting receptor-interacting protein kinase-1 (RIPK1)/receptor-interacting protein kinase-3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) signal pathway. Methods Sixty SPF SD rats were randomly divided into the sham operation group, the model group, the miR-NC group, the miR-139-5p mimic group and the miR-139-5p mimic+RIPK1 inhibitor Nec-1 group (miR-139-5p mimic+Nec-1 group), with 12 rats in each group. Except the sham group, the other groups used permanent ligation of bilateral common carotid arteries to construct rat CCH model. New object recognition experiment and Morris water maze were used to evaluate the cognitive function of rats. Enzyme linked immunosorbent assay (ELISA) was used to detect levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory factor tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) in rat hippocampus. Real-time quantitative PCR (qPCR) was used to detect the expression of miR-139-5p, RIPK1, RIPK3, MLKL mRNA in rat hippocampus. Western blot method was used to detect the protein expression levels of RIPK1, RIPK3, MLKL, synaptophysin (SYP), postsynaptic density protein 95 (PSD95) and α-synuclein (α-SYN). Double luciferase reporter gene experiment was used to verify the relationship between miR-139-5p and RIPK1. Results Compared with the sham group, the resolution coefficient, target quadrant residence time, levels of miR-139-5p, GSH-Px, SOD and the protein expression levels of SYP and PSD95 decreased obviously in hippocampus of the model group rats (P<0.05). The escape latency extended, and levels of MDA, TNF-α and IL-6 in hippocampus increased. The mRNA and protein expression of RIPK1, RIPK2, MLKL, the protein expression of α-SYN increased obviously (P<0.05). Compared with the model group and the miR-NC group, the expression trends of related indexes were opposite to the above in the miR-139-5p mimic group (P<0.05). Nec-1 further promoted the recovery of cognitive function in CCH rats by up-regulating the expression of miR-139-5p (P<0.05). MiR-139-5p negatively regulated the expression of RIPK1. Conclusion The up regulation of miR-139-5p may alleviate the cognitive dysfunction of CCH rats by targeting the inhibition of RIPK1/RIPK3/MLKL signaling pathway.

Key words: cognitive dysfunction, RIPK1/RIPK3/MLKL pathway, MicroRNA-139-5p, chronic cerebral hypoperfusion

中图分类号:

R743.3

图/表 7

参考文献 24

[1]	DUNCOMBE J, KITAMURA A, HASE Y, et al. Chronic cerebral hypoperfusion:A key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia[J]. Clin Sci(Lond), 2017, 131(19):2451-2468. doi:10.1042/CS20160727.
[2]	YAN N, XU Z, QU C, et al. Dimethyl fumarate improves cognitive deficits in chronic cerebral hypoperfusion rats by alleviating inflammation,oxidative stress,and ferroptosis via NRF2/ARE/NF-κB signal pathway[J]. Int Immunopharmacol, 2021, 98:107844. doi:10.1016/j.intimp.2021.107844.
[3]	SU S H, WU Y F, LIN Q, et al. URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion[J]. J Neuroinflammation, 2019, 16(1):260. doi:10.1186/s12974-019-1668-0.
[4]	BI X, FENG Y, WU Z, et al. Electroacupuncture attenuates cognitive impairment in rat model of chronic cerebral hypoperfusion via miR-137/NOX4 axis[J]. Evid Based Complement Alternat Med, 2021, 2021:8842022. doi:10.1155/2021/8842022.
[5]	MAO M, XU Y, ZHANG X Y, et al. MicroRNA-195 prevents hippocampal microglial/macrophage polarization towards the M1 phenotype induced by chronic brain hypoperfusion through regulating CX3CL1/CX3CR1 signaling[J]. J Neuroinflammation, 2020, 17(1):244. doi:10.1186/s12974-020-01919-w.
[6]	YAN M L, ZHANG S, ZHAO H M, et al. MicroRNA-153 impairs presynaptic plasticity by blocking vesicle release following chronic brain hypoperfusion[J]. Cell Commun Signal, 2020, 18(1):57. doi:10.1186/s12964-020-00551-8.
[7]	YAO Y, HU S, ZHANG C, et al. Ginsenoside Rd attenuates cerebral ischemia/reperfusion injury by exerting an anti-pyroptotic effect via the miR-139-5p/FoxO1/Keap1/Nrf2 axis[J]. Int Immunopharmacol, 2022, 105:108582. doi:10.1016/j.intimp.2022.108582.
[8]	ZHANG Y Y, LIU W N, LI Y Q, et al. Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway[J]. Naunyn Schmiedebergs Arch Pharmacol, 2019, 392(9):1085-1095. doi:10.1007/s00210-019-01656-9.
[9]	DENG X X, LI S S, SUN F Y. Necrostatin-1 prevents necroptosis in brains after ischemic stroke via inhibition of RIPK1-mediated RIPK3/MLKL signaling[J]. Aging Dis, 2019, 10(4):807-817. doi:10.14336/AD.2018.0728.
[10]	欧阳梦琪, 舒佳慧, 张棋, 等. 辣椒素对慢性脑低灌注大鼠认知行为受损及海马线粒体-内质网结构偶联表达的影响[J]. 中国病理生理杂志, 2019, 35(8):1393-1402.
	OUYANG M Q, SHU J H, ZHANG Q, et al. Effects of capsaicin on cognitive impairment and mitochondria-associated endoplasmic reticulum membranes in rats with chronic cerebral hypoper-fusion[J]. Chinese Journal of Pathophysiolog, 2019, 35(8):1393-1402. doi:10.3969/j.issn.1000-4718.2019.08.008.
[11]	陈胜, 王春明, 严雪飞, 等. 特异性坏死性凋亡抑制剂-1(Nec-1)减轻脊髓损伤模型大鼠胶质瘢痕的形成[J]. 基础医学与临床, 2022, 42(1):94-99.
	CHEN S, WANG C M, YAN X F, et al. Specific necroptosis inhibitor-1(Nec-1)attenuates glial scar formation in rat models with spinal cord injury[J]. Basic Clin Med, 2022, 42(1):94-99. doi:10.3969/j.issn.1001-6325.2022.01.016.
[12]	WAN Q, MA X, ZHANG Z J, et al. Ginsenoside reduces cognitive impairment during chronic cerebral hypoperfusion through brain-derived neurotrophic factor regulated by epigenetic modulation[J]. Mol Neurobiol, 2017, 54(4):2889-2900. doi:10.1007/s12035-016-9868-4.
[13]	HAM P B 3rd, RAJU R. Mitochondrial function in hypoxic ischemic injury and influence of aging[J]. Prog Neurobiol, 2017, 157:92-116. doi:10.1016/j.pneurobio.2016.06.006.
[14]	何婧, 黄燕, 杜果, 等. 慢性脑低灌注致模型大鼠学习记忆受损及海马α-突触核蛋白变化[J]. 中国组织工程研究, 2018, 22(20):3230-3236.
	HE J, HUANG Y, DU G, et al. Cognitive impairment and hippocampal alpha-synuclein change in a rat model of chronic cerebral hypoperfusion[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(20):3230-3236. doi:10.3969/j.issn.2095-4344.0311.
[15]	董雯, 刘奔, 伦永志. 白藜芦醇对长期高热量饮食小鼠的认知功能保护及突触相关机制研究[J]. 中国现代应用药学, 2020, 37(14):1692-1697.
	DONG W, LIU B, LUN Y Z. Study on the cognitive function protection and synaptic mechanism of resveratrol on mice fed with long-term high-calorie diet[J]. Chin J Mod Appl Pharm, 2020, 37(14):1692-1697. doi:10.13748/j.cnki.issn1007-7693.2020.14.005.
[16]	CASALETTO K, RAMOS-MIGUEL A, VANDEBUNTE A, et al. Late-life physical activity relates to brain tissue synaptic integrity markers in older adults[J]. Alzheimers Dement, 2022, 18(11):2023-2035. doi:10.1002/alz.12530.
[17]	COLEY A A, GAO W J. PSD95:A synaptic protein implicated in schizophrenia or autism?[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2018, 82:187-194. doi:10.1016/j.pnpbp.2017.11.016.
[18]	王玲, 张盼盼, 付爱双, 等. 间歇低氧对大鼠海马神经细胞突触相关蛋白表达及认知功能的影响[J]. 中华老年心脑血管病杂志, 2020, 22(5):534-537.
	WANG L, ZHANG P P, FU A S, et al. Effects of intermittent hypoxia on synapse-related protein expression and cognitive function of hippocampal neurons in rats[J]. Chin J Geriatr Heart Brain Vessel Dis, 2020, 22(5):534-537. doi:10.3969/j.issn.1009-0126.2020.05.021.
[19]	陈景, 杨磊, 左亚杰, 等. 黄芩苷改善慢性脑低灌注大鼠认知障碍的作用及机制研究[J]. 中南药学, 2021, 19(7):1333-1338.
	CHEN J, YANG L, ZUO Y J, et al. Effect of baicalin on cognitive impairment in rats with chronic cerebral hypoperfusion and its mechanism[J]. Central South Pharmacy, 2021, 19(7):1333-1338. doi:10.7539/j.issn.1672-2981.2021.07.013.
[20]	MEHRA S, SAHAY S, MAJI S K. α-Synuclein misfolding and aggregation:Implications in Parkinson's disease pathogenesis[J]. Biochim Biophys Acta Proteins Proteom, 2019, 1867(10):890-908. doi:10.1016/j.bbapap.2019.03.001.
[21]	KIM S, KWON S H, KAM T I, et al. Transneuronal propagation of pathologic α-Synuclein from the gut to the brain models Parkinson's disease[J]. Neuron, 2019, 103(4):627-641.e7. doi:10.1016/j.neuron.2019.05.035.
[22]	PALMAS M F, ETZI M, PISANU A, et al. The intranigral infusion of human-alpha synuclein oligomers induces a cognitive impairment in rats associated with changes in neuronal firing and neuroinflammation in the anterior cingulate cortex[J]. Cells, 2022, 11(17):2628. doi:10.3390/cells11172628.
[23]	LIU X, LV X, LIU Z, et al. MircoRNA-29a in astrocyte-derived extracellular vesicles suppresses brain ischemia reperfusion injury via TP53INP1 and the NF-κB/NLRP3 axis[J]. Cell Mol Neurobiol, 2022, 42(5):1487-1500. doi:10.1007/s10571-021-01040-3.
[24]	WANG Q S, LUO X Y, FU H, et al. MiR-139 protects against oxygen-glucose deprivation/reoxygenation(OGD/R)-induced nerve injury through targeting c-Jun to inhibit NLRP3 inflammasome activation[J]. J Stroke Cerebrovasc Dis, 2020, 29(9):105037. doi:10.1016/j.jstrokecerebrovasdis.2020.105037.

基因名称	引物序列（5'→3'）	产物大小/bp
miR-139- 5p	上游：CAGCAGTGGCAGAGTGCG	159
miR-139- 5p	下游：CGATCCAGCCTACCTAGAGTGCA	159
RIPK1	上游：TTCATGGTGCACAAACCCCT	121
RIPK1	下游：TGACACAAGCGCAACAAAGG	121
RIPK3	上游：CATCGATCTCTCTCGTGGGC	185
RIPK3	下游：CGTACACGTAGTCCCACTCG	185
MLKL	上游：GGGAACACTCCACGGAAACA	117
MLKL	下游：GATCTTGCAGTCTCTCGGGG	117
U6	上游：GGTCAGCCAGCTCAAGCGTC	136
U6	下游：TGGACACGCTCGCTCTGAATCG	136
β-actin	上游：CCCGCGAGTACAACCTTCTT	98
β-actin	下游：AGGGTCAGGATGCCTCTCTT	98

基因名称	引物序列（5'→3'）	产物大小/bp
miR-139- 5p	上游：CAGCAGTGGCAGAGTGCG	159
miR-139- 5p	下游：CGATCCAGCCTACCTAGAGTGCA	159
RIPK1	上游：TTCATGGTGCACAAACCCCT	121
RIPK1	下游：TGACACAAGCGCAACAAAGG	121
RIPK3	上游：CATCGATCTCTCTCGTGGGC	185
RIPK3	下游：CGTACACGTAGTCCCACTCG	185
MLKL	上游：GGGAACACTCCACGGAAACA	117
MLKL	下游：GATCTTGCAGTCTCTCGGGG	117
U6	上游：GGTCAGCCAGCTCAAGCGTC	136
U6	下游：TGGACACGCTCGCTCTGAATCG	136
β-actin	上游：CCCGCGAGTACAACCTTCTT	98
β-actin	下游：AGGGTCAGGATGCCTCTCTT	98

组别	1 d	2 d	3 d	4 d	5 d
Sham组	30.28±3.75	26.62±3.37	24.39±2.72	20.38±2.30	16.60±1.87
Model组	53.65±5.02^a	50.40±4.16^a	48.45±4.21^a	45.32±3.85^a	41.06±3.77^a
miR-NC组	53.23±4.86	50.06±4.22	48.64±4.26	45.53±4.08	41.65±3.51
miR-139-5p mimic组	42.36±3.25^bc	37.14±3.54^bc	33.71±2.92^bc	29.42±2.39^bc	25.37±2.14^bc
miR-139-5p mimic+Nec-1组	33.55±2.38^d	28.10±1.95^d	25.55±1.67^d	22.83±1.23^d	18.62±1.15^d
F	88.897^＊＊	125.718^＊＊	154.959^＊＊	199.106^＊＊	241.944^＊＊

组别	1 d	2 d	3 d	4 d	5 d
Sham组	30.28±3.75	26.62±3.37	24.39±2.72	20.38±2.30	16.60±1.87
Model组	53.65±5.02^a	50.40±4.16^a	48.45±4.21^a	45.32±3.85^a	41.06±3.77^a
miR-NC组	53.23±4.86	50.06±4.22	48.64±4.26	45.53±4.08	41.65±3.51
miR-139-5p mimic组	42.36±3.25^bc	37.14±3.54^bc	33.71±2.92^bc	29.42±2.39^bc	25.37±2.14^bc
miR-139-5p mimic+Nec-1组	33.55±2.38^d	28.10±1.95^d	25.55±1.67^d	22.83±1.23^d	18.62±1.15^d
F	88.897^＊＊	125.718^＊＊	154.959^＊＊	199.106^＊＊	241.944^＊＊

组别	GSH-Px/（kU/g）	SOD/（kU/g）	MDA/（mmol/g）	TNF-α/（ng/L）	IL-6/（ng/L）
Sham组	28.04±3.36	50.47±2.63	0.78±0.08	95.15±9.24	12.53±1.14
Model组	8.67±0.95^a	12.24±0.88^a	3.24±0.25^a	316.42±26.32^a	58.63±6.05^a
miR-NC组	8.96±0.78	11.82±0.95	3.12±0.21	309.48±27.26	57.03±5.76
miR-139-5p mimic组	16.83±1.22^bc	26.41±2.38^bc	1.18±0.09^bc	248.37±25.40^bc	30.28±2.51^bc
miR-139-5p mimic+Nec-1组	27.74±2.30^d	43.10±3.59^d	0.80±0.03^d	176.45±16.34^d	16.49±1.73^d
F	140.124^＊＊	343.236^＊＊	383.479^＊＊	108.404^＊＊	178.559^＊＊

MiR-139-5p靶向RIPK1/RIPK3/MLKL信号通路对慢性脑低灌注大鼠认知障碍的影响

Influence of miR-139-5p on cognitive dysfunction in rats with chronic cerebral hypoperfusion by targeting RIPK1/RIPK3/MLKL signal pathway

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 7

参考文献 24

相关文章 15

编辑推荐

Metrics

本文评价

组别	miR-139 -5p	RIPK1	RIPK3	MLKL
Sham组	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
Model组	0.31±0.03^a	2.24±0.20^a	1.97±0.18^a	2.16±0.20^a
miR-NC组	0.30±0.03	2.20±0.21	1.95±0.19	2.12±0.21
miR-139-5p mimic组	0.66±0.08^bc	1.64±0.13^bc	1.58±0.09^bc	1.65±0.10^bc
miR-139-5p mimic+Nec-1组	0.89±0.09	1.15±0.06^d	1.23±0.03^d	1.28±0.04^d
F	191.724^＊＊	94.870^＊＊	71.818^＊＊	81.511^＊＊

组别	RIPK1	RIPK3	MLKL	SYP	PSD95	α-SYN
Sham组	0.21±0.02	0.24±0.02	0.17±0.02	0.87±0.08	0.82±0.08	0.15±0.02
Model组	0.86±0.08^a	0.90±0.09^a	0.81±0.08^a	0.23±0.02^a	0.19±0.02^a	0.76±0.07^a
miR-NC组	0.83±0.08	0.92±0.08	0.79±0.08	0.21±0.02	0.18±0.02	0.77±0.07
miR-139-5p mimic组	0.55±0.03^bc	0.41±0.04^bc	0.48±0.03^bc	0.56±0.05^bc	0.42±0.06^bc	0.38±0.03^bc
miR-139-5p mimic+Nec-1组	0.38±0.02^d	0.29±0.02^d	0.23±0.01^d	0.75±0.08^d	0.80±0.08^d	0.20±0.02^d
F	164.338^＊＊	196.456^＊＊	191.366^＊＊	166.360^＊＊	188.145^＊＊	232.096^＊＊

[1]	肖雨倩, 孙可心, 万俊, 陈淑颖, 陈丽敏, 王岩, 白艳杰. RNA m6A甲基化在卒中后认知障碍中的研究进展[J]. 天津医药, 2024, 52(3): 331-336.
[2]	李晓晓, 白艳杰, 王岩, 张雍闯, 陈丽敏, 陈淑颖. 高脂饮食与认知障碍关系的研究进展[J]. 天津医药, 2023, 51(4): 441-444.
[3]	李艳, 刘琼, 黄萱, 刘丽江. 芦丁对慢性脑低灌注大鼠海马组织神经元损伤及RhoA/ROCK信号通路的影响[J]. 天津医药, 2022, 50(12): 1270-1275.
[4]	闫春晓, 李培越, 郑启秘, 邹晓, 李建波. 阿尔茨海默病患者血清中Apelin13和FKBP5的表达水平及临床意义[J]. 天津医药, 2022, 50(10): 1088-1092.
[5]	门慧, 金香兰, 赵世娇, 王莹, 李施新, 周晶 . 血清白蛋白水平与急性缺血性卒中患者认知功能的相关性[J]. 天津医药, 2021, 49(6): 613-616.
[6]	彭金芝, 李晓东, 王乾兴. 氯胺酮滥用致认知障碍与海马改变的研究进展[J]. 天津医药, 2021, 49(4): 444-448.
[7]	郭一丹, 田茹, 罗洋. 老年血液透析患者血清同型半胱氨酸与认知损伤相关性的临床研究[J]. 天津医药, 2019, 47(3): 295-298.
[8]	王志勇, 徐磊. 急性呼吸窘迫综合征存活者长期结局研究进展[J]. 天津医药, 2018, 46(6): 600-605.
[9]	王计伟1， 2,王毅1,王东1,周源1,陈芳莲2,崔维韻2,刘丽2,张建宁1， 2△. 不同程度颅脑创伤大鼠外周血内皮祖细胞动态变化及伤后认知能力的研究[J]. 天津医药, 2018, 46(2): 139-143.
[10]	李花娟 1，朱婧 1，张挺 2，宋毅军 1△. 轻度认知障碍工作记忆中 theta 振荡的特征研究[J]. 天津医药, 2017, 45(6): 605-609.
[11]	薛刘军，魏明，郑金龙. 边缘区卒中后对学习记忆认知功能的影响[J]. 天津医药, 2017, 45(10): 1033-1035.
[12]	吴振华 1， 2，郭志刚 2，林云佳 2，李培军 2. 颈动脉评估与非体外循环冠脉旁路移植术后患者认知障碍的相关性[J]. 天津医药, 2015, 43(6): 631-634.
[13]	张云飞，高伟忠，马世颖，刘金碧. 右美托咪定对老年人髋部手术后认知功能障碍的影响[J]. 天津医药, 2015, 43(6): 663-665.
[14]	姚扬. 轻度认知障碍患者血管狭窄程度与脑电图功率谱改变的关系[J]. , 2014, 42(1): 74-75 .
[15]	郭连雨. 2型糖尿病合并轻度认知功能障碍的危险因素分析[J]. , 2013, 41(8): 0-746 .