抑制小凹蛋白减轻大鼠脑缺血/再灌注诱导的神经功能损伤

doi:10.16352/j.issn.1001-6325.2022.12.1879

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (12): 1879-1884.doi: 10.16352/j.issn.1001-6325.2022.12.1879

抑制小凹蛋白减轻大鼠脑缺血/再灌注诱导的神经功能损伤

陈宁宁¹, 应新旺², 谢庆凤^2*

1.浙江中医药大学附属温州市中医院康复科,浙江温州 325000;
2.温州医科大学附属第二医院育英儿童医院康复医学中心,浙江温州 325000

收稿日期:2022-04-12 修回日期:2022-09-29 出版日期:2022-12-05 发布日期:2022-11-23
通讯作者: ^* 1103211071@qq.com
基金资助:
温州市科研项目 (Y20210164); 浙江省自然科学基金(LQ21H170003)

Inhibition of p-caveolin1 attenuates neurological injury induced by cerebral ischemia-reperfusion in rats

CHEN Ning-ning¹, YING Xin-wang², XIE Qing-feng^2*

1. Department of Physical Medicine and Rehabilitation, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Wenzhou 325000;
2. Department of Physical Medicine and Rehabilitation, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China

Received:2022-04-12 Revised:2022-09-29 Online:2022-12-05 Published:2022-11-23
Contact: ^* 1103211071@qq.com

摘要/Abstract

摘要： 目的探讨小凹蛋白1(Cav1)的磷酸化在大鼠脑缺血/再灌注后神经功能损伤中的作用机制。方法将大鼠随机分为假手术组(sham)、模型组(model)和抑制剂组(PP2)。用改良神经功能缺损评分(mNSS)评价大鼠神经功能,氯化三苯基四氮唑(TTC)染色检测脑梗死体积,Nissl染色检测脑缺血/再灌注后组织形态,Tunel染色检测梗死灶周围细胞凋亡数量, Western blot和免疫荧光检测脑梗死周围组织中p-Cav1、胶质纤维酸性蛋白(GFAP)和离子钙结合接头分子1(Iba1)的表达。结果与假手术组相比, 模型组大鼠mNSS评分增加(P＜0.05);脑梗死体积明显增加(P＜0.05),尼氏体数量减少(P＜0.05);凋亡细胞数量增加(P＜0.05);p-Cav1、GFAP和Iba1蛋白的表达量上调(P＜0.05)。而抑制剂PP2能减轻上述指标的变化,保护脑缺血/再灌注损伤大鼠神经功能(P＜0.05)。结论抑制p-Cav1可以改善大鼠脑缺血/再灌注后神经功能,其机制可能与抑制胶质细胞激活及相互作用有关。

关键词: 脑缺血/再灌注, 星形胶质细胞, 小胶质细胞, 小凹蛋白1

Abstract: Objective To explore the mechanism of phosphorylation of caveolin1 (Cav1) in neurological injury after cerebral ischemia-reperfusion in rats. Methods The rats were randomly divided into sham group, model group and inhibitor group(PP2). Neurological function was evaluated by modified neurological deficit score (mNSS) neurobehavioral score, cerebral infarction volume was evaluated by triphenyltetrazolium chloride (TTC) staining, histomorphology after cerebral ischemia-reperfusion was evaluated by Nissl staining, and apoptosis of peri-infarcted tissue was detected by Tunel staining. Western blot and immunofluorescence were used to detect the protein expression of p-Cav1, glial fibrillary acidic protein (GFAP) and ion calcium binding junction molecule 1 (Iba1) in the tissue around cerebral infarction. Results Compared with the sham operation group, there were significantly increased mNSS score, volume of cerebral infarction, number of apoptotic cells and expression of p-Cav1, GFAP and Iba1 in the model group,while the number of Nissl corpuscles decreased. The inhibitor PP2 reduced the changes of the above-mentioned indexes and protect the neurological function of rats with cerebral ischemia-reperfusion injury. Conclusions Inhibition of p-Cav1 may improve the neurological function after cerebral ischemia-reperfusion in rats with potential mechanism of inhibiting glial cell activation and interaction.

Key words: cerebral ischemia-reperfusion, astrocytes, microglia, caveolin 1

中图分类号:

R332
R34

陈宁宁, 应新旺, 谢庆凤. 抑制小凹蛋白减轻大鼠脑缺血/再灌注诱导的神经功能损伤[J]. 基础医学与临床, 2022, 42(12): 1879-1884.

CHEN Ning-ning, YING Xin-wang, XIE Qing-feng. Inhibition of p-caveolin1 attenuates neurological injury induced by cerebral ischemia-reperfusion in rats[J]. Basic & Clinical Medicine, 2022, 42(12): 1879-1884.

参考文献 14

[1]	GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet Neurol, 2021, 20: 795-820.
[2]	Lancet. 21st century management and prevention of stroke[J]. Lancet, 2018, 392: 1167. doi: 10.1016/S0140-6736(18)32358-4.
[3]	Li B, Huang Z, Meng J, et al. MiR-202-5p attenuates neurological deficits and neuronal injury in MCAO model rats and OGD-induced injury in Neuro-2a cells by targeting eIF4E-mediated induction of autophagy and inhibition of Akt/GSK-3β pathway[J]. Mol Cell Probes, 2020, 51:101497. doi: 10.1016/j.mcp.2019.101497.
[4]	Li H, Tian JL, Yin Y, et al. Interleukin-18 mediated inflammatory brain injury after intracerebral hemorrhage in male mice[J]. J Neurosci Res,2020, 100:1359-1369.
[5]	Xie HM, Su X, Zhang FY, et al. rofile of the RNA in exosomes from astrocytes and microglia using deep sequencing: implications for neurodegeneration mechanisms[J]. Neural Regen Res, 2022, 17: 608-617.
[6]	Wang S, Head BP. Caveolin-1 in stroke neuropathology and neuroprotection: A novel molecular therapeutic target for ischemic-related injury[J]. Curr Vasc Pharmacol, 2019, 17: 41-49.
[7]	Zhang X, Ram Rez CM, Aryal B, et al. Cav-1 (Caveolin-1) deficiency increases autophagy in the endothelium and attenuates vascular inflammation and atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2020, 40: 1510-1522.
[8]	Bai Y, Xu G, Xu M, et al. Inhibition of Src phosphorylation reduces damage to the blood-brain barrier following transient focal cerebral ischemia in rats[J]. Int J Mol Med, 2014, 34: 1473-1482.
[9]	Liu DZ, Ander BP, Xu H, et al. Blood-brain barrier breakdown and repair by Src after thrombin-induced injury[J]. Ann Neurol, 2010, 67: 526-533.
[10]	郭壮, 周利君. 星形胶质细胞-小胶质细胞的交互对话在神经炎症中的双重作用[J]. 实用医学杂志, 2021, 37: 2432-2436.
[11]	Cheng Y, Song Y, Chen H, et al. Ferroptosis mediated by lipid reactive oxygen species: a possible causal link of neuroinflammation to neurological disorders[J]. Oxid Med Cell Longew, 2021, 2021:5005136. doi: 10.1155/2021/5005136.
[12]	Belayev L, Hong SH, Menghani H, et al. Docosanoids promote neurogenesis and angiogenesis, blood-brain barrier integrity, penumbra protection, and neurobehavioral recovery after experimental ischemic stroke[J]. Mol Neurobiol, 2018, 55: 7090-7106.
[13]	Liu M, Xu Z, Wang L, et al. Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte[J]. J Neuroinflammation, 2020, 17: 270-285. doi: 10.1186/s12974-020-01946-7
[14]	Benveniste EN. Cytokine actions in the central nervous system[J]. Cytokine Growth Factor Rev, 1998, 9: 259-275.

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抑制小凹蛋白减轻大鼠脑缺血/再灌注诱导的神经功能损伤

Inhibition of p-caveolin1 attenuates neurological injury induced by cerebral ischemia-reperfusion in rats

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