[1]田径,董艳,刘刚,等.二甲双胍减轻脂多糖诱导的脓毒症小鼠脑损伤[J].第三军医大学学报,2019,41(15):1423-1430.
 TIAN Jing,DONG Yan,LIU Gang,et al.Metformin attenuates brain damage in mouse model of lipopolysaccharide-induced sepsis[J].J Third Mil Med Univ,2019,41(15):1423-1430.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第15期
页码:
1423-1430
栏目:
基础医学
出版日期:
2019-08-15

文章信息/Info

Title:
Metformin attenuates brain damage in mouse model of lipopolysaccharide-induced sepsis
作者:
田径董艳刘刚 张力唐玲
重庆医科大学附属大学城医院:神经中心,急诊科;重庆医科大学基础医学院病理生理学教研室
Author(s):
TIAN Jing DONG Yan LIU GangZHANG Li TANG Ling

Center of Neuroscience, Department of Emergency, University-Town Hospital of Chongqing Medical University, Chongqing, 401331; Department of Pathophysiology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China

关键词:
二甲双胍炎症脂多糖脓毒症脑损伤
Keywords:
metformin inflammation lipopolysaccharide sepsis brain damage
分类号:
R631; R742.06; R977.15
文献标志码:
A
摘要:

目的 探讨二甲双胍对脂多糖(lipopolysaccharide, LPS)诱导的脓毒症小鼠脑损伤的作用。方法 雄性BALB/c小鼠104只采用随机数字表法分为4组,每组26只,分别为对照组、单纯二甲双胍组、LPS组、LPS+二甲双胍组。腹腔注射脂多糖(LPS,20 mg/kg)诱发脓毒症建立模型。注射LPS前30 min予二甲双胍(400 mg/kg)腹腔注射,注射LPS后18 h时即观察终点取脑组织、血清进行检测:HE染色观察脑组织形态学改变,EB染色法测定血脑屏障通透性;相应试剂盒测定脑组织Caspase-3活性、MDA含量和IL-6、TNF-α、MPO水平以及血清NSE、S100-β水平。结果 海马CA1、CA3区和大脑皮层形态学观察:LPS组大量神经细胞变性,而LPS+二甲双胍组神经元变性减轻。EB、NSE、S100-β:LPS组较对照组升高(P<0.05),LPS+二甲双胍组较LPS组降低(P<0.05)。Caspase-3:LPS组较对照组增加(P<0.01);LPS+二甲双胍组较LPS组降低(P<0.05),较余两组升高(P<0.05)。IL-6、TNF-α、MPO:LPS组较对照组增高(P<0.05),LPS+二甲双胍组较LPS组降低(P<0.05)。MDA:LPS组较对照组升高(P<0.01),LPS+二甲双胍组较LPS组降低(P<0.01)。结论 二甲双胍可以减轻脂多糖诱导的脓毒症小鼠的脑损伤,其机制可能是保护血脑屏障、抑制凋亡、抗炎及减少氧化应激。二甲双胍对脓毒症诱发的脑损伤有治疗价值。

Abstract:

Objective To explore the mitigative effect of metformin on brain damage in mice with lipopolysaccharide (LPS)-induced sepsis. MethodsA total of 104 male BALB/c mice were randomly divided into 4 groups (n=26), that is, control, metformin, LPS and LPS+metformin group. LPS of 20 mg/kg was intraperitoneally injected to mice to induce sepsis-like systemic inflammation, and metformin (400 mg/kg) was given intraperitoneally in 0.5 h before LPS injection. Serum and brain samples were harvested 18 h after LPS administration. HE staining was performed for the histological observation in the brain tissues. Evans blue staining was used to evaluate the permeability of the blood-brain barrier (BBB). The activity of Caspase-3, content of malondialdehyde (MDA), and levels of IL-6,TNF-α and myeloperoxidase (MPO) in brain samples, and the levels of neuron-specific enolase (NSE) and soluble protein100-β (S100-β) in serum were determined with corresponding reagent testing kits. ResultsIn the morphological observation on hippocampal CA1 and CA3 regions and cerebral cortex, the results indicated that LPS exposure induced large quantities of widespreading degenerative neurons, and these abnormalities were attenuated in mice receiving metformin administration. The elevated Evans blue content in the brain from LPS-insulted mice was decreased by metformin (P<0.05). Treatment with metformin suppressed LPS-induced elevation of NSE and S100-β in the serum (P<0.05). The activity of Caspase-3 was significantly higher in LPS group than the control group (P<0.01), while the activity of Caspase-3 in LPS+metformin group was lower than in LPS group (P<0.05), which was higher than that in control group and metformin group (P<0.05). Metformin treatment decreased the contents of IL-6, TNF-α and MPO in the brain tissue from LPS-insulted mice (P<0.05). In addition, metformin treatment inhibited LPS-induced increase of MDA in brain tissue (P<0.01). ConclusionMetformin alleviates LPS-induced brain damage, which may associated with protection of BBB, inhibition of apoptosis, suppressed inflammatory response and attenuated oxidative stress. Metformin might have therapeutic value in sepsis-associated brain damage.

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更新日期/Last Update: 2019-08-13