[1]宋秀威 杨月君 王伟.五味子乙素调节MAPK/NF-κB/AP-1信号通路对缺血性脑卒中大鼠神经元损伤的影响[J].卒中与神经疾病杂志,2023,30(03):242-248.[doi:10.3969/j.issn.1007-0478.2023.03.002]
　Song Xiuwei*,Yang Yuejun,Wang Wei..Schisandrin B attenuates neuronal damage in rats with ischemic stroke by regulating MAPK/NF-κB/AP-1 signaling pathway[J].Stroke and Nervous Diseases,2023,30(03):242-248.[doi:10.3969/j.issn.1007-0478.2023.03.002]
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五味子乙素调节MAPK/NF-κB/AP-1信号通路对缺血性脑卒中大鼠神经元损伤的影响()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第30卷
期数:
2023年03期
页码:
242-248
栏目:
论著
出版日期:
2023-06-20

文章信息/Info

Title:
Schisandrin B attenuates neuronal damage in rats with ischemic stroke by regulating MAPK/NF-κB/AP-1 signaling pathway
文章编号:
1007-0478(2023)03-0242-07
作者:
宋秀威 杨月君 王伟
071000 河北省保定市第二医院健康体检科(宋秀威),神经内科(杨月君),功能检查科(王伟)
Author(s):
Song Xiuwei*;  Yang Yuejun;  Wang Wei.
*Department of Physical Examination, the NO.2 Hospital of Baoding, Baoding 071000
关键词:
五味子乙素; 丝裂原活化蛋白激酶/核转录因子-κB/激活蛋白-1; 缺血性脑卒中; 大鼠; 神经元损伤
Keywords:
Schisandrin B; MAPK/NF-κB/AP-1; Ischemic stroke; Rats; Neuronal damage
分类号:
R743.3
DOI:
10.3969/j.issn.1007-0478.2023.03.002
文献标志码:
A
摘要:
目的 探究五味子乙素(Schisandrin B,Sch B)调节丝裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)/核转录因子-κB(Nuclear factor-kappa beta,NF-κB)/激活蛋白-1(Activator protein-1,AP-1)信号通路对缺血性脑卒中大鼠神经元损伤的影响。方法 选用SD大鼠144只,随机分为6组(24只/组):Sham组、Model组、Sch B低剂量组(10 mg/kg Sch B)、Sch B中剂量组(20 mg/kg Sch B)、Sch B高剂量组(40 mg/kg Sch B)、激活剂组[40 mg/kg Sch B+2 mg/kg茴香霉素(Anisomycin)]; 采用改良线栓法致大鼠大脑中动脉闭塞(Middle cerebral artery occlusion,MCAO),建立缺血性脑卒中(Ischemic stroke,IS)模型; 对各组大鼠进行Loeffler神经学评分以评估大鼠神经功能缺损程度; 氯化三苯基四氮唑(2,3,5-Triphenyltetrazolium chloride,TTC)染色测定大鼠脑梗死面积; 称重法检测大鼠脑组织含水量; 苏木精-伊红染色法(Hematoxylin-eosinstaining,HE)观察大鼠脑组织损伤; 原位末端标记染色法(TdT-mediated dUTP Nick-End Labeling,TUNEL)观察大鼠神经细胞凋亡情况; 二氯荧光素双醋酸盐(2',7'-Dichlorodihydrofluorescin diacetate,DCFH-DA)荧光探针法检测大鼠脑组织活性氧(Reactive oxygen species,ROS)水平; 分别使用超氧化物歧化酶(Superoxidedismutase,SOD)、丙二醛(Malondialdehyde,MDA)试剂盒检测脑组织SOD活性与MDA水平; western blot检测脑组织中增殖细胞核抗原(Proliferating cell nuclear antigen,PCNA)、凋亡相关蛋白[BCL-2关联X蛋白(Bcl-2associated X protein,Bax)、半胱氨酸蛋白酶3(Cysteine proteinase3,Caspase-3)]、自噬相关蛋白[微管相关蛋白1轻链3Ⅱ(Microtubule-associated protein 1 light chain 3II,LC3Ⅱ)、卷曲螺旋肌球蛋白样BCL2结合蛋白(Coiled-coil myosin-like BCL2 interacting protein,Beclin-1)]和MAPK/NF-κB/AP-1通路蛋白的表达水平。结果 与Sham组比较,Model组大鼠脑组织中SOD活性减弱、神经学评分、PCNA蛋白表达水平降低,病理损伤加重、脑梗死面积百分比、脑组织含水量、神经细胞凋亡率、ROS,MDA水平、Bax,Caspase-3,LC3Ⅱ/LC3Ⅰ,Beclin-1、磷酸化-P38丝裂原活化蛋白激酶(p-p38 Mitogen-activated protein kinase,p-p38MAPK)/p38丝裂原活化蛋白激酶(p38 Mitogen-activated protein kinase,p38 MAPK)、磷酸化-核转录因子-κB p65(p-Nuclear transcription factor kappa-B p65,p-NF-κB p65)/核转录因子-κB p65(Nuclear transcription factor kappa-B p65,NF-κB p65)、AP-1蛋白表达水平升高(P<0.05); 与Model组比较,Sch B低、中、高剂量组大鼠SOD活性增强、神经学评分、PCNA蛋白表达水平升高,病理损伤减轻、脑梗死面积百分比、脑组织含水量、神经细胞凋亡率、ROS,MDA水平、Bax,Caspase-3,LC3Ⅱ/LC3Ⅰ,Beclin-1,p-p38MAPK/p38MAPK,p-NF-κB p65/NF-κB p65,AP-1蛋白表达水平降低(P<0.05); 与Sch B高剂量组比较,激活剂组大鼠脑组织中SOD活性减弱、神经学评分、PCNA蛋白表达水平降低,病理损伤加重、脑梗死面积百分比、脑组织含水量、神经细胞凋亡率、ROS,MDA水平、Bax,Caspase-3,LC3Ⅱ/LC3Ⅰ,Beclin-1,p-p38MAPK/p38MAPK,p-NF-κB p65/NF-κB p65,AP-1蛋白表达水平升高(P<0.05)。结论 Sch B通过抑制MAPK/NF-κB/AP-1信号通路,从而减轻缺血性脑卒中大鼠的神经元损伤。
Abstract:
ObjectiveTo investigate the effect of Schisandrin B(Sch B), which regulates the mitogen-activated protein kinase(MAPK)/nuclear factor-κB(NF-κB)/activator protein-1(AP-1)signaling pathway, on neuronal injury in rats with ischemic stroke.Methods A total of 144 SD rats were randomly divided into 6 groups(24 rats/group): Sham group, Model group, Sch B low-dose group(10 mg/kg Sch B), Sch B medium-dose group(20 mg/kg Sch B), Sch B high-dose group(40 mg/kg Sch B), and activator group(40 mg/kg Sch B + 2 mg/kg anisomycin). The ischemic stroke(IS)model was established by middle cerebral artery occlusion(MCAO)in rats using a modified suture method. Loeffler neurological scoring was performed in each group to assess the degree of neurological impairment in rats. TTC staining was used to determine the area of cerebral infarction. The water content of brain tissue was measured by weighing. HE staining was used to observe brain tissue damage. TUNEL staining was used to observe the apoptosis of neural cells. DCFH-DA was used as a fluorescent probe to detect reactive oxygen species(ROS)in brain tissue. The levels of reactive oxygen species(ROS)in rat brain tissues were measured by fluorescence probe. SOD activity and MDA levels were measured by superoxide dismutase(SOD)and malondialdehyde(MDA)kits, respectively. Western blotting was applied to detect proliferating cell nuclear antigen(PCNA), apoptosis-related proteins(Bax, caspase-3), autophagy-related proteins(LC3II, Beclin-1), and the MAPK/NF-κB/AP-1 pathway in brain tissues.Results Compared with the Sham group, the Model group showed diminished SOD activity, reduced neurological score, PCNA level, increased pathological injury, percentage of cerebral infarct area, brain tissue water content, apoptosis rate of neural cells, ROS, MDA level, Bax, caspase-3, LC3II/LC3Ⅰ, Beclin-1, p-p38MAPK/p38MAPK, p-NF-κB p65/NF-κB p65 and AP-1 levels(P<0.05). Compared with the Model group, the rats in the Sch B low, medium, and high dose groups showed enhanced SOD activity, neurological scores, increased PCNA protein expression levels, reduced pathological injury, percentage of cerebral infarct area, brain tissue water content, neuronal apoptosis rate, ROS, amount of MDA levels, Bax, caspase-3, LC3II/LC3 I, Beclin-1, p-p38MAPK/p38MAPK, p-NF-κB p65/NF-κB p65, and AP-1 protein expression levels were reduced(P<0.05). Compared with the Sch B high-dose group, the activator group showed reduced SOD activity, neurological scores, PCNA protein expression levels in rat brain tissues, aggravated pathological injury, brain infarction percentage of area, brain tissue water content, neuroapoptosis rate, ROS, MDA level, Bax, caspase-3, LC3II/LC3Ⅰ, Beclin-1, p-p38MAPK/p38MAPK, p-NF-κB p65/NF-κB p65, and AP-1 protein expression levels were increased in the activator group compared with the Sch B high-dose group(P<0.05).Conclusion Sch B attenuates neuronal injury in ischemic stroke rats by inhibiting the MAPK/NF-κB/AP-1 signaling pathway.

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更新日期/Last Update: 2023-06-20