芍药内酯苷对新生缺氧缺血性脑损伤小鼠的神经保护的实验研究

doi:10.3969/j.issn.1006-6233.2022.09.02

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摘要 目的: 观察芍药内酯苷对新生缺氧缺血性脑损伤小鼠脑细胞凋亡、氧化应激及炎症的影响,并探究其潜在机制。方法: 构建新生小鼠缺氧性脑损伤(Hypoxic Ischemic Encephalopathy,HIE)模型。30 mg/kg芍药内酯苷给模型小鼠灌胃给药,设为芍药内酯苷组;假手术组、模型组小鼠等量灌胃蒸馏水。2,3,5-氯化三苯基四氮唑(Triphenyltetrazolium chloride,TTC)染色检测小鼠脑梗死面积,脱氧核苷酸末端转移酶(TdT-mediated dUTP-biotin nick end labeling,Tunel)法检测脑细胞凋亡,蛋白免疫印迹(Western blot ,WB)检测组织活化的胱天蛋白酶3(Cleaved caspase-3)、Cleaved caspase-9、磷脂酰肌醇3-激酶(Phosphatidylinositol 3-kinase,PI3K)、磷酸化(Phosphorylation,p)-PI3K、丝氨酸/苏氨酸激酶(Serine / threonine kinase,AKT)、p-AKT、雷帕霉素哺乳动物靶点(Mammalian target of rapamycin,mTOR)、p-mTOR的蛋白表达;酶联免疫吸附试验(Enzyme linked immunosorbent assay,ELISA)实验检测脑组织丙二醛(Malondialdehyde ,MDA)、超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽(Glutathione,GSH)、白细胞介素(Interleukin,IL)-6、IL-18、IL-1β;免疫组织化学法检测脑组织细胞间黏附分子-1(Intercellular cell adhesion molecule-1,ICAM-1)。结果: 与假手术组相比,模型组小鼠脑梗死率显著升高,脑细胞凋亡率、Cleaved caspase-3、Cleaved caspase-9蛋白均显著升高,脑组织MDA、ICAM-1、IL-6、IL-18、IL-1β均升高,SOD、GSH降低,脑组织p-PI3K、p-AKT、p-mTOR均降低(P<0.05)。芍药内酯苷治疗组小鼠上述指标均明显趋于假手术组。结论: 芍药内酯苷减轻HIE幼鼠脑梗死,抑制脑细胞凋亡、氧化应激、炎症反应,保护幼鼠神经损伤,其机制与激活PI3K/AKT/mTOR信号通路有关。

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	阳梅
	李明玉
	李德渊

关键词 ：新生小鼠缺氧缺血性脑损伤, 芍药内酯苷, PI3K/AKT/mTOR信号通路

Abstract：Objective: To observe the effects of albiflorin on brain cell apoptosis, oxidative stress, and inflammation in neonatal hypoxic-ischemic brain injury mice and to explore its potential mechanism. Methods: The hypoxic brain injury (HIE) model of neonatal mice was established. 30 mg/kg albiflorin was administered by gavage to model mice, which were set as albiflorin group. Mice in the sham operation group and model group were given distilled water by gavage. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was used to measure the area of cerebral infarction, TDT mediated dUTP biotin nick end labeling (Tunel) method was used to measure brain cell apoptosis, and Western blot (WB) was used to measure protein expression of activated Caspase-3, cleaved caspase-9 phosphatidylinositol 3-kinase (PI3K), phosphorylation (p) - PI3K, serine/threonine kinase (AKT), p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR in brain tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), interleukin (IL)-6, IL-18, and IL-1β in brain tissue. Intercellular cell adhesion molecule-1 (ICAM-1) was detected by immunohistochemistry. Results: Compared with the sham operation group, the cerebral infarction rate, brain cell apoptosis rate, cleaved caspase-3 and cleaved caspase-9 protein, MDA, ICAM-1, IL-6, IL-18, and IL-1β in the model group were significantly increased, and SOD, GSH, p-PI3K, p-AKT and p-mTOR decreased in brain tissue (P<0.05). The above indexes of mice in the albiflorin treatment group were significantly closer to those in the sham operation group. Conclusions: AAlbiflorin alleviates cerebral infarction in HIE young rats, inhibits brain cell apoptosis, oxidative stress, and inflammatory response, and protects against nerve injury in young rats. Its mechanism may be related to the activation of the PI3K / Akt / mTOR signal pathway.

Key words： Hypoxic-ischemic brain injury in neonatal mice Albiflorin PI3K/AKT/mTOR signal path

基金资助:四川省卫生和计划生育科研课题,(编号:16PJ240)

引用本文:

阳梅, 李明玉, 李德渊. 芍药内酯苷对新生缺氧缺血性脑损伤小鼠的神经保护的实验研究[J]. 河北医学, 2022, 28(9): 1414-1419.
YANG Mei, LI Mingyu, et al. Experimental Study on the Neuroprotection of Albiflorin in Mice with Neonatal Hypoxic-Ischemic Brain Injury. HeBei Med, 2022, 28(9): 1414-1419.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2022.09.02 或 http://www.hbyxzzs.cn/CN/Y2022/V28/I9/1414

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