急性脑梗死小鼠脑组织中Galectin-3和MMP-9的表达及尼莫地平的干预作用

doi:10.13481/j.1671-587x.20200320

摘要/Abstract

摘要： 目的：探讨半乳糖凝集素3（Galectin-3）和基质金属蛋白酶9（MMP-9）在急性脑梗死小鼠脑组织中的表达及尼莫地平的干预作用，阐明Galectin-3和MMP-9在脑梗死发病和治疗中的作用。方法：将210只小鼠随机分为对照组、模型组和尼莫地平组，每组70只。模型组和尼莫地平组小鼠采用线栓法建立急性脑梗死模型，尼莫地平组小鼠于术前30 min腹腔注射尼莫地平。Longar评分和改良神经功能缺损评分（mNSS）评价各组小鼠神经功能，TTC染色检测各组小鼠脑梗死体积，检测各组小鼠脑组织含水量，HE染色观察各组小鼠脑组织形态学表现，RT-PCR法检测各组小鼠脑组织中Galectin-3和MMP-9 mRNA表达水平，免疫组织化学染色测定各组小鼠脑组织中Galectin-3和MMP-9蛋白表达水平。结果：与对照组比较，模型组小鼠Longar评分和mNSS升高（P<0.05），脑梗死体积和脑组织含水量明显升高（P<0.05），脑组织中Galectin-3和MMP-9 mRNA表达水平升高（P<0.05），脑组织中Galectin-3和MMP-9蛋白表达水平升高（P<0.05）。与模型组比较，尼莫地平组小鼠Longar评分和mNSS评分降低（P<0.05），脑梗死体积和脑组织含水量降低（P<0.05），脑组织中Galectin-3和MMP-9 mRNA表达水平降低（P<0.05），脑组织中Galectin-3和MMP-9蛋白表达水平降低（P<0.05）。对照组小鼠脑细胞形态和结构正常；模型组小鼠脑细胞出现水肿和片状坏死，可见炎细胞浸润；尼莫地平组小鼠脑细胞水肿和坏死较轻。结论：尼莫地平可通过降低脑组织Galectin-3和MMP-9表达发挥对脑梗死小鼠脑组织的保护作用。

关键词: 半乳糖凝集素3, 基质金属蛋白酶9, 脑梗死, 尼莫地平

Abstract: Objective: To investigate the expressions of Galectin-3 and matrix metalloproteinase-9(MMP-9) in brain tissue of the mice with acute cerebral infarction and the intervention effect of nimodipine,and to elucidate the effects of Galectin-3 and MMP-9 in the occurrence and treatment of cerebral infarction. Methods: A total of 210 mice were randomly divided into control group, model group and nimodipine group (n=70).In model group and nimodipine group, the acute cerebral infarction models of mice were established by the suture method.The mice in nimodipine group were intraperitoneally injected with nimodipine 30 min before operation.The Longar score and modified neurological severity score (mNSS) were used to evaluate the neurological function of the mice in various groups,the cerebral infarction volumes of the mice in various groups were determined by TTC staining,the water contents in brain tissue of the mice in various groups were detected, HE staining was used to observe the morphology of brain tissue of the mice in various groups, the expression levels of Galectin-3 and MMP-9 mRNA in brain tissue of the mice in various groups were detected by RT-PCR method,and the expression levels of Galectin-3 and MMP-9 proteins in brain tissue of the mice in various groups were detected by immunohistochemical staining. Results: Compared with control group, the Longar score and mNSS of the mice in model group were increased(P<0.05),the cerebral infarction volume and water content in brain tissue of the mice in model group were significantly increased(P<0.05), the expression levels of Galectin-3 and MMP-9 mRNA in brain tissue were increased(P<0.05),and the expression levels of Galectin-3 and MMP-9 proteins in brain tissue were increased(P<0.05).Compared with model group, the Longar score and mNSS of the mice in nimodipine group were decreased (P<0.05),the cerebral infarction volume and the water content in brain tissue were decreased(P<0.05),the expression levels of Galectin-3 and MMP-9 mRNA in brain tissue were decreased(P<0.05), and the expression levels of Galectin-3 and MMP-9 proteins were decreased(P<0.05).The morphology and structure of brain cells of the mice in control group were normal;the brain cells of the mice in model group showed edema and flaky necrosis, and the inflammatory cell infiltration was found; the brain cells of the mice in nimodipine group showed mild edema and necrosis. Conclusion: Nimodipine can protect the brain tissue of the mice with cerebral infarction by reducing the expressions of Galectin-3 and MMP-9.

Key words: Galectin-3, matrix metalloproteinase 9, cerebral infarction, nimodipine

中图分类号:

R743.33

卜一, 张硕, 钱旭东, 王红梅, 窦志杰. 急性脑梗死小鼠脑组织中Galectin-3和MMP-9的表达及尼莫地平的干预作用[J]. 吉林大学学报(医学版), 2020, 46(03): 551-556.

BU Yi, ZHANG Shuo, QIAN Xudong, WANG Hongmei, DOU Zhijie. Expressions of Galectin-3 and MMP-9 in brain tissue of mice with acute cerebral infarction and intervention effect of nimodipine[J]. Journal of Jilin University(Medicine Edition), 2020, 46(03): 551-556.

参考文献

[1] THACKERAY J T, HUPE H C, WANG Y,et al.Myocardial inflammation predicts remodeling and neuroinflammation after myocardial infarction[J].J Am Coll Cardiol,2018,71(3):263-275.
[2] TSAI H F, WU C S, CHEN Y L,et al.Galectin-3 suppresses mucosal inflammation and reduces disease severity in experimental colitis[J].J Mol Med (Berl),2016,94(5):545-556.
[3] LI Y, LIU H, XU L.Expression of MMP-9 in different degrees of chronic hepatitis B and its correlation with inflammation[J].Exp Ther Med,2018,16(5):4136-4140.
[4] NISHIKAWA H, NAKATSUKA Y, SHIBA M,et al.increased plasma galectin-3 preceding the development of delayed cerebral infarction and eventual poor outcome in non-severe aneurysmal subarachnoid hemorrhage[J].Transl Stroke Res,2018,9(2):110-119.
[5] FANNING J P, SEE HOE L E, PASSMORE M R,et al.neuron-specific enolase andmatrix metalloproteinase 9 signal perioperative silent brain infarctionduring or after transcatheter aortic valve implantation[J].Am J Cardiol,2019,123(3):434-439.
[6] HISAMATSU K, NIWA M, KOBAYASHI K,et al.Galectin-3 expression in hippocampal CA2 following transient forebrain ischemia and its inhibition by hypothermia or antiapoptotic agents[J].Neuroreport,2016,27(5):311-317.
[7] 王翊飞,张李涛,褚正民,等.前列地尔注射液联合尼莫地平注射液治疗动脉瘤性蛛网膜下腔出血伴脑血管痉挛的临床研究[J].中国临床药理学杂志,2016,32(21):1942-1945,1949.
[8] MORAN J M, PEDRERA-ZAMORANO J D.Comments on "Efficacy and safety assessment of acupuncture andnimodipineto treat mild cognitive impairment after cerebralinfarction:a randomized controlled trial"[J].BMC Complement Altern Med,2017,17(1):119-120.
[9] 刘天易.芍药苷对大鼠脑缺血再灌注损伤细胞凋亡的影响及其作用机制[J].西部中医药,2016,29(5):8-11.
[10] 张文芳,王东,崔景晶.最佳线栓头端直径建立对小鼠脑缺血再灌注模型成功率的影响[J].中国康复医学杂志,2019,34(4):386-391.
[11] 秦彦强,孙忠人,张亚娟, 等.针刺预处理对脑梗死大鼠胆碱能抗炎通路的影响研究[J].实用心脑肺血管病杂志,2015,23(3):29-33.
[12] 姜炎,连亚军.鼠神经生长因子对急性脑梗死大鼠炎性因子与神经功能的影响[J].中华实验外科杂志,2016,33(7):1819-1821.
[13] MEDVEDEVA E A, BEREZIN I I, SHCHUKIN Y V.Galectin-3, markers of oxidative stress and renal dysfunction in patients with chronic heart failure[J].Kardiologiia,2017,57(3):46-50.
[14] 刘浪.急性脑梗死患者颈动脉硬化程度与血清Galectin-3表达水平的关系及阿托伐他汀钙的干预作用[J].卒中与神经疾病,2017,24(5):420-422,426.
[15] FAN F, YANG J, XU Y,et al.MiR-539 targetsMMP-9 to regulate the permeability of blood-brainbarrier in ischemia/reperfusion injury of brain[J].Neurochem Res,2018,43(12):2260-2267.
[16] SARAMI FOROSHANI M, SOBHANI Z S, et al.Fullerenol nanoparticles decrease blood-brain barrier interruption and brainedema during cerebral ischemia-reperfusion injury probably by reduction of interleukin-6 and matrix metalloproteinase-9 transcription[J].J Stroke Cerebrovasc Dis,2018,27(11):3053-3065.
[17] CHEN L, YANG Q, DING R,et al.Carotid thickness and atherosclerotic plaque stability, serum inflammation, serum MMP-2 and MMP-9 were associated with acute cerebral infarction[J].Exp Ther Med,2018,16(6):5253-5257.
[18] KAJITANI K, YANAGIMOTO K, NAKABEPPU Y.Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia:implications for the role of inflammation[J].Psychopharmacology (Berl),2017,234(19):2919-2927.
[19] 仲琳,梁平平,龚磊, 等.半乳糖凝集素3对内皮细胞生长、迁移及炎症反应的影响[J].中国病理生理杂志,2017,33(6):1065-1072.
[20] 车楠,李莉,李良昌, 等.桦褐孔菌多糖通过PI3K/Akt/NF-κB/MMP-9抑制哮喘小鼠气道重构[J].中国免疫学杂志,2018,34(11):1654-1657.
[21] 解晓燕,李旭,宋江庆,等.依达拉奉联合尼莫地平对颅脑损伤患者氧化应激、炎症因子的影响[J].海南医学院学报,2016,22(21):2527-2529.
[22] TANG Y D, ZHENG X S, YING T T,et al.Nimodipine-mediated re-myelination after facial nerve crush injury in rats[J].J Clin Neurosci,2015,22(10):1661-1668.