五味子乙素对大鼠脑缺血再灌注损伤的保护作用及其机制

doi:10.13481/j.1671-587x.20160504

吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (05): 860-865.doi: 10.13481/j.1671-587x.20160504

五味子乙素对大鼠脑缺血再灌注损伤的保护作用及其机制

姜恩平¹, 唐泽立¹, 于春艳², 于春荣³, 朱伟¹

1. 广东医科大学基础医学院病理学教研室, 广东东莞 523808;
2. 北华大学基础医学院病理学教研室, 吉林吉林 132013;
3. 国家食品药品监督管理总局药品审评中心, 北京 100038

收稿日期:2016-01-26 出版日期:2016-09-28 发布日期:2016-09-29
通讯作者: 朱伟,副教授,硕士研究生导师(Tel:0769-22896401,E-mail:gdmczw@126.com);于春荣,副研究员,硕士研究生导师(Tel:010-68921464,E-mail:bjsycr@126.com) E-mail:gdmczw@126.com;bjsycr@126.com
作者简介:姜恩平(1975-),女,吉林省吉林市人,副教授,医学博士,主要从事心血管药理及肿瘤药理学方面的研究。
基金资助:
国家自然科学基金资助课题（81472275）；广东省卫计委医学科研基金资助课题（A2015372）

Protective effect of schisandrin B on cerebral ischemia reperfusion injury of rats and its mechanisms

JIANG Enping¹, TANG Zeli¹, YU Chunyan², YU Chunrong³, ZHU Wei¹

1. Department of Pathology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan 523808, China;
2. Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin 132013, China;
3. Center for Drug Evaluation, China Food and Drug Administration, Beijing 100038, China

Received:2016-01-26 Online:2016-09-28 Published:2016-09-29

摘要/Abstract

摘要：

目的：观察五味子乙素（SchB）对大鼠脑缺血再灌注损伤的保护作用及对HSPA12B/PI3K/Akt信号通路的影响，并探讨其作用机制。方法：将130只SD大鼠随机分为假手术组、脑缺血再灌注损伤模型组（模型组）、低剂量五味子乙素组（SchB 3 mg·kg^-1，SchB₁组）、中剂量五味子乙素组（SchB 10 mg·kg^-1，SchB₂组）和高剂量五味子乙素组（SchB 30 mg·kg^-1，SchB₃组）。假手术组大鼠不插栓线；模型组大鼠建立脑缺血2 h再灌注22 h模型；SchB₁、SchB₂和SchB₃组分别用不同剂量的SchB预先给药7 d后再造模。神经功能缺损评分检测大鼠神经功能障碍情况，通过脑组织含水量的测定检测脑组织水肿情况，甲苯胺蓝染色检测脑组织形态学改变，ELISA法检测脑组织匀浆中核因子kappa B（NF-κB）、肿瘤坏死因子α（TNF-α）、白细胞介素1（IL-1）和白细胞介素6（IL-6）水平，Western blotting法检测脑组织中热休克蛋白A12B（HSPA12B）、丝氨酸/苏氨酸蛋白激酶（Akt）和磷酸化的丝氨酸/苏氨酸蛋白激酶（p-Akt）表达水平。结果：与假手术组比较，模型组大鼠神经功能评分明显升高（P<0.01），脑组织含水量升高（P<0.01），脑组织结构疏松，间质出现水肿，NF-κB、TNF-α、IL-1和IL-6水平升高（P<0.01），HSPA12B和p-Akt蛋白表达水平降低（P<0.01）；与模型组比较，SchB₁、SchB₂和SchB₃组大鼠神经功能评分明显降低（P<0.01），SchB₂和SchB₃组脑组织含水量减少（P<0.05），神经细胞水肿减轻，空泡减少，NF-κB、TNF-α、IL-1和IL-6水平降低（P<0.05或P<0.01），SchB₂和SchB₃组HSPA12B蛋白表达水平升高（P<0.05），SchB₁、SchB₂和SchB₃组p-Akt蛋白表达水平升高（P<0.01）。结论：SchB对大鼠脑缺血再灌注损伤具有一定的保护作用，其机制可能与调控HSPA12B/PI3K/Akt信号通路、抑制再灌注时炎症反应对神经细胞的损伤有关。

关键词: 五味子乙素, 脑缺血再灌注损伤, 热休克蛋白A12B, 信号通路

Abstract:

Objective: To investigate the protective effect of schisandrin B (SchB) on the cerebral ischemia reperfusion injury of the rats and the influence in HSPA12B/PI3K/Akt signaling pathway, and to explore the mechanisms.Methods: 130 SD rats were divided into sham group, cerebral ischemia reperfusion injury model group (model group), low dose of SchB group(SchB 3 mg·kg^-1, SchB₁ group), middle dose of SchB group(SchB 10 mg·kg^-1, SchB₂ group)and high dose of SchB group(SchB 30 mg·kg^-1, SchB₃ group)(n=26). The rats in sham group didn't plug lines; the rats in model were used to establish ischemia reperfusion models; the rats in SchB₁, SchB₂ and SchB₃ groups were firstly pretreated with different doses of SchB for 7 d, and then they were used to build cerebral ischemia reperfusion injury models. The nerve dysfunction of rats was evaluated by neurologic deficit score. The cerebral edema was detected by measuring the content of water in brain tissue. The morphological changes of brain tissue were observed by toluidine blue staining. The levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) in the brain tissue were detected by ELISA. Western blotting method was used to detect the protein expression levels of heat shock protein A12B (HSPA12B), serine-threonine kinase (Akt) and phosphorylation serine-threonine kinase (p-AKT). Results: Compared with sham group, the neurologic deficit score of rats in model group was significantly increased (P<0.01), and the content of water in brain tissue was increased (P<0.01); the brain tissue structure was loosened, and the mesenchyme appeared edema; the NF-κB, TNF-α, IL-1, and IL-6 levels were increased (P<0.01), and the expression levels of HSPA12B and p-Akt proteins were decreased (P<0.01). Compared with model group, the neurologic deficit scores of the rats in SchB₁, SchB₂, and SchB₃ groups were decreased (P<0.01), and the contents of water in brain tissue of the rats in SchB₂ and SchB₃ groups were decreased (P<0.05); the edema of nerve cells was alleviated, and the cavities were reduced; the NF-κB, TNF-α, IL-1, and IL-6 levels were decreased (P<0.05 or P<0.01), the expression levels of the HSPA12B protein in SchB₂, and SchB₃ groups were increased (P<0.05), and the p-Akt protein expression levels of the rats in SchB₁, SchB₂, and SchB₃ groups were increased (P<0.01). Conclusion: SchB could protect the cerebral ischemia reperfusion injury of rats, its mechanism may be related to regulating the HSPA12B/PI3K/Akt signaling pathway and inhibiting the inflammatory reaction damage to the nerve cells of reperfusion.

Key words: schisandrin B, cerebral ischemia reperfusion injury, heat shock protein A12B, signaling pathway

中图分类号:

R285.5

姜恩平, 唐泽立, 于春艳, 于春荣, 朱伟. 五味子乙素对大鼠脑缺血再灌注损伤的保护作用及其机制[J]. 吉林大学学报(医学版), 2016, 42(05): 860-865.

JIANG Enping, TANG Zeli, YU Chunyan, YU Chunrong, ZHU Wei. Protective effect of schisandrin B on cerebral ischemia reperfusion injury of rats and its mechanisms[J]. Journal of Jilin University Medicine Edition, 2016, 42(05): 860-865.

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五味子乙素对大鼠脑缺血再灌注损伤的保护作用及其机制

Protective effect of schisandrin B on cerebral ischemia reperfusion injury of rats and its mechanisms

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