大黄素对缺血性脑卒中模型大鼠的神经保护作用及其对ERK1/2信号通路的影响

doi:10.13481/j.1671-587x.20190604

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (06): 1212-1217.doi: 10.13481/j.1671-587x.20190604

大黄素对缺血性脑卒中模型大鼠的神经保护作用及其对ERK1/2信号通路的影响

潘峰¹, 郭夏青², 沈江宜³, 苏志强⁴

1. 郑州大学附属医院南阳市中心医院神经内科, 河南南阳 473000;
2. 河南大学淮河医院神经内科, 河南开封 475000;
3. 河南省南阳市南石医院神经重症医学科, 河南南阳 473000;
4. 哈尔滨医科大学第一临床医院神经内科, 黑龙江哈尔滨 150001

收稿日期:2019-02-01 出版日期:2019-12-05 发布日期:2019-12-05
通讯作者: 潘峰,主治医师(Tel:0377-63200026,E-mail:fengpanfp8808@163.com) E-mail:fengpanfp8808@163.com
作者简介:潘峰(1985-),男,河南省南阳市人,主治医师,医学硕士,主要从事神经内科相关疾病治疗方面的研究。
基金资助:
国家自然科学基金资助课题（8177052088）

Neuroprotective effect of emodin on ischemic stroke model rats and its effect on ERK1/2 signaling pathway

PAN Feng¹, GUO Xiaqing², SHEN Jiangyi³, SU Zhiqiang⁴

1. Department of Neurology, Nanyang Central Hospital, Affiliated Hospital, Zhengzhou University, Nanyang 473000, China;
2. Department of Neurology, Huaihe Hospital, Henan University, Kaifeng 475000, China;
3. Department of Intensive Care Unit, Nanshi Hospital, Nanyang City, Henan Province, Nanyang 473000, China;
4. Department of Neurology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China

Received:2019-02-01 Online:2019-12-05 Published:2019-12-05

摘要/Abstract

摘要： 目的：研究大黄素对缺血性脑卒中模型大鼠的神经保护作用及其对细胞外调节蛋白激酶1/2（ERK1/2）信号通路的影响，探讨大黄素保护缺血性脑卒中的机制。方法：将200只大鼠随机分为假手术组（n=60）、模型组（n=70）和大黄素组（n=70）。模型组和大黄素组大鼠建立缺血性脑卒中模型，大黄素组大鼠在建模前30 min给予大黄素腹腔注射。评定各组大鼠神经功能障碍评分、脑梗死体积和脑组织含水量，免疫组织化学染色测定各组大鼠缺血侧脑组织皮质细胞凋亡率，Western blotting法测定各组大鼠缺血侧脑组织中Cleavedcaspase-3、Bcl-2相关X蛋白（Bax）、B淋巴细胞瘤2（Bcl-2）、ERK1/2和磷酸化-ERK1/2（p-ERK1/2）蛋白表达水平。结果：假手术组大鼠无神经功能障碍和脑梗死灶；大黄素组大鼠神经功能障碍评分和脑梗死体积均明显低于模型组（t=8.331，t=3.538，P<0.05）。与模型组比较，大黄素组大鼠脑组织含水量降低（t=9.507，P<0.05），缺血侧脑组织皮质细胞凋亡率降低（t=57.593，P<0.05），缺血侧脑组织中Cleavedcaspase-3、Bax和p-ERK1/2蛋白表达水平降低（t=4.088，t=4.463，t=10.659，P<0.05），Bcl-2蛋白表达水平升高（t=5.035，P<0.05）。结论：大黄素可能通过抑制ERK1/2信号通路抑制神经细胞凋亡发挥对缺血性脑卒中大鼠的神经保护作用。

关键词: 大黄素, 缺血性脑卒中, 神经保护, 细胞外调节蛋白激酶, 细胞凋亡

Abstract: Objective: To study the neuroprotective effect of emodin in the model rats with ischemic stroke and its effect the on extracellular regulated protein kinase1/2 (ERK1/2) signaling pathway, and to explore the mechanism of protective effect of emodin on the ischemic stroke. Methods: A total of 200 rats were randomly divided into sham operation group (n=60 rats), model group (n=70) and emodin group (n=70). The rat models of ischemic stroke were established in model group and emodin group. The rats in emodin group were injected intraperitoneally with emodin 30 min before modeling. The neurological dysfunction scores, cerebral infarction volumes and water contents in brain tissue of the rats in various groups were measured; immunohistochemical staining was used to determine the apoptotic rates of ischemic lateral cortex cells of the rats in various groups;Western blotting method was used to determine the expression levels of Cleaved caspase-3, Bcl-2 related X protein (Bax), B lymphocyte tumor-2 (Bcl-2), ERK1/2 and phosphorylation-ERK1/2 (p-ERK1/2) proteins of the rats in various groups. Results: The rats in sham operation group had no neurological dysfunction and cerebral infarction. The neurological dysfunction score and cerebral infarction volume of the rats in emodin group were significantly lower than those in model group (t=8.331, t=3.538, P<0.05).Compared with model group, the water content in brain tissue of the rats in emodin group was decreased (t=9.507, P<0.05), the apoptotic rate of cerebral cortex cells was decreased (t=57.593,P<0.05), the expression levels of Cleaved caspase-3, Bax, and p-ERK1/2 proteins in ischemic brain tissue were decreased (t=4.088, t=4.463, t=10.659, P<0.05), and the expression level of Bcl-2 protein in ischemic brain tissue was increased (t=5.035, P<0.05). Conclusion: Emodin may inhibit the neuronal apoptosis by inhibiting the ERK1/2 signaling pathway to exert the neuroprotective effect on the rats with ischemic stroke.

Key words: emodin, ischemic stroke, neuroprotection, extracellular regulated protein kinase, apoptosis

中图分类号:

R743.3

潘峰, 郭夏青, 沈江宜, 苏志强. 大黄素对缺血性脑卒中模型大鼠的神经保护作用及其对ERK1/2信号通路的影响[J]. 吉林大学学报(医学版), 2019, 45(06): 1212-1217.

PAN Feng, GUO Xiaqing, SHEN Jiangyi, SU Zhiqiang. Neuroprotective effect of emodin on ischemic stroke model rats and its effect on ERK1/2 signaling pathway[J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1212-1217.

参考文献

[1] SYLAJA P N, PANDIAN J D, KAUL S,et al. Ischemic stroke profile, risk factors, and outcomes in india[J]. Stroke, 2019, 49(1):219-222.
[2] YANG H J, XI X X, ZHAO B,et al.KLF4 protects brain microvascular endothelial cells from ischemic stroke induced apoptosis by transcriptionally activating MALAT1[J].Biochem Biophys Res Commun,2018,495(3):2376-2382.
[3] MA Y, XIA X, CHENG J M,et al. Emodin inhibits inducible nitric oxide synthase in a rat model of craniocerebral explosive injury[J]. Neurochem Res, 2014, 39(9):1809-1816.
[4] GUO H L, SHEN X R, XU Y,et al.Emodin prevents hypoxic-ischemic neuronal injury: Involvement of the activin A pathway[J].Neural Regen Res,2013,8(15):1360-1367.
[5] 谭力,王联英,向海鹰,等.大黄素对脑缺血再灌注大鼠的保护作用及机制研究[J].中西医结合心脑血管病杂志,2010,8(9):1100-1101.
[6] LONGA E Z, WEINSTEIN P R, CARLSON S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[7] TALKE P, BICKLER P E. Effects of dexmedetomidine on hypoxia-evoked glutamate release and glutamate receptor activity in hippocampal slices[J]. Anesthesiology, 1996, 85(3):551-557.
[8] BALAGANAPATHY P, BAIK S H, MALLILANKARAMAN K,et al.Interplay between Notch and p53 promotes neuronal cell death in ischemic stroke[J].J Cereb Blood Flow Metab,2018,38(10):1781-1795.
[9] CHANG Q Y, LIN Y W, HSIEH C L.Acupuncture and neuroregeneration in ischemic stroke[J].Neural Regen Res,2018,13(4):573-583.
[10] ZHAO T F, FU Y X, SUN H,et al.Ligustrazine suppresses neuron apoptosis via the Bax/Bcl-2 and caspase-3 pathway in PC12 cells and in rats with vascular dementia[J].IUBMB Life,2018,70(1):60-70.
[11] WEN H L, WU Z, HU H D,et al.The anti-tumor effect of pachymic acid on osteosarcoma cells by inducing PTEN and Caspase 3/7-dependent apoptosis[J].J Nat Med,2018,72(1):57-63.
[12] PANNEER SELVAM S, ROTH B M, NGANGA R,et al.Balance between senescence and apoptosis is regulated by telomere damage-induced association between p16 and caspase-3[J].J Biol Chem,2018,293(25):9784-9800.
[13] DANIELE S, PIETROBONO D, COSTA B,et al.Bax activation blocks self-renewal and induces apoptosis of human glioblastoma stem cells[J].ACS Chem Neurosci,2018,9(1):85-99.
[14] GUO X W, XIANG C X, ZHANG Z T,et al.Displacement of bax by BMF mediates STARD133’UTR-induced breast cancer cellsapoptosisin an miRNA-depedent manner[J].Mol Pharm,2018,15(1):63-71.
[15] EDLICH F. BCL-2 proteins andapoptosis: Recent insights and unknowns[J].Biochem Biophys Res Commun,2018,500(1):26-34.
[16] PEÑA-BLANCOA, GARCÍA-SÁEZ A J.Bax, Bak and beyond-mitochondrial performance in apoptosis[J].FEBS J,2018,285(3):416-431.
[17] 张雯, 宋俊科, 杜冠华. 缺血再灌注损伤与细胞凋亡信号转导通路[J]. 中国药学杂志, 2015, 50(7):565-569.
[18] PARK H, AHN S H, JUNG Y,et al.Leptin suppresses glutamate-induced? apoptosisthrough regulation of ERK1/2 signaling pathways in rat primary astrocytes[J].Cell Physiol Biochem,2017,44(6):2117-2128.
[19] ELUKA-OKOLUDOH E, EWUNKEM A J, THORPE S,et al. Diepoxybutane-inducedapoptosis is mediated through the ERK1/2 pathway[J].Hum Exp Toxicol,2018,37(10):1080-1091.
[20] 苏洲,田小军,王玉梅, 等.依达拉奉对急性缺血性脑卒中患者丝裂原活化蛋白激酶/细胞外调节蛋白激酶信号通路蛋白表达的影响[J].中华老年医学杂志,2018,37(12):1372-1375.
[21] 罗素,荣晓凤,彭菲菲.大黄素对TNF-α诱导的成纤维样滑膜细胞株MH7A细胞ERK1/2和p38MAPK的影响[J].免疫学杂志,2017,33(2):113-117.
[22] 王青,周联,董燕, 等.大黄素对HT-29细胞MAPKs信号通路活化及IL-8分泌的影响[J].现代生物医学进展,2011,11(11):2087-2089.
[23] 杨海蕾,陈晨,屈秋民.社区脑卒中高危人群颈动脉粥样硬化与缺血性脑卒中的关系[J/OL].西安交通大学学报:医学版,2019[2019-11-18].http://kns.cnki.net/kcms/detail/61.1399.R.20191009.1055.006.htm

大黄素对缺血性脑卒中模型大鼠的神经保护作用及其对ERK1/2信号通路的影响

Neuroprotective effect of emodin on ischemic stroke model rats and its effect on ERK1/2 signaling pathway

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