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大黄素对脓毒症小鼠急性脑损伤的神经保护作用
作者:董艳 刘刚 张力 唐玲 
单位:401331 重庆 重庆医科大学附属大学城医院神经内科(董艳、唐玲) 急诊科(刘刚) 400016 重庆 重庆医科大学病理生理学教研室(张力) 
关键词:大黄素 炎症 脓毒症 脑损伤 
分类号:R965.1
出版年,卷(期):页码:2019,44(1):13-19
摘要:

[摘要]  目的  探讨大黄素(emodin)对脓毒症小鼠急性脑损伤的神经保护作用及其机制。方法  将雄性BALB/c 小鼠随机分为4组:正常对照组、脂多糖(LPS)组、大黄素组和大黄素+LPS组。大黄素组和大黄素+LPS组在建模前30min给予20mg/kg大黄素预处理,其余两组给予相同体积溶剂,LPS组和大黄素+LPS组用15mg/kg LPS刺激,其余两组在此期间给予相同体积生理盐水。LPS注射后18h处死动物,采集脑组织和血浆标本。HE染色观察脑组织病理学改变,酶联免疫标记法(ELISA)检测血浆S100β蛋白表达以评估颅脑损伤程度,比色定量法检测脑组织中乳酸(LA)以评估代谢紊乱程度,ELISA法检测血浆中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平以评估全身炎性反应的程度, ELISA法检测血浆神经特异性烯醇化酶(NSE)水平表达以评估神经炎性反应程度,比色定量法测定脑组织中乙酰胆碱酯酶(Ach-E)活力以评估脑内乙酰胆碱(Ach)水平。结果  与正常对照组比较,LPS组出现明显脑组织病理损伤,大黄素组未出现明显脑组织病理损伤;与LPS组相比,大黄素+LPS组脑组织损伤程度明显减轻。LPS组脑组织中Ach-ELA 水平[分别为(1.09±0.10)U/mg protein(0.35±0.03)mmol/g protein]明显高于正常对照组[(0.84±0.09)U/mg protein(0.16±0.03)mmol/g proteinP<0.05]LPS组血浆中S100βIL-6TNF-αNSE水平[分别为(0.52±0.06)ng/ml(4207.23±90.76)pg/ml(355.62±6.88)pg/ml(9.02±0.78)ng/ml]也明显高于正常对照组[分别为(0.38±0.05)ng/ml(501.60±74.18)pg/ml(157.41±10.65)pg/ml(5.41±0.89)ng/mlP<0.05],而大黄素组与正常对照组间以上指标差异均无统计学意义(P>0.05);与LPS组比较,大黄素+LPS组血浆中S100β[(0.44±0.06)ng/ml]IL-6[(1479.50±50.53)pg/ml]TNF-α[(213.48±9.19)pg/ml]NSE[(6.74±1.12)ng/ml]水平明显降低(P<0.05),脑组织中LA[(0.25±0.03)mmol/g protein]Ach-E[(0.87±0.07)U/mg protein]水平也明显降低(P<0.05)结论  大黄素对LPS诱导的小鼠急性脑损伤具有保护作用,其机制可能与激活胆碱能抗炎通路和抑制炎性反应有关。

[Abstract]  Objective  To investigate the neuroprotective effect and corresponding mechanism of emodin on acute brain injury in sepsis mice. Methods  Male BALB/c mice were randomly divided into four groups: normal control group, lipopolysaccharide (LPS) group, emodin group and emodin+LPS group. Mice in emodin group and emodin+LPS group were administered with emodin (20mg/kg) 30min before modeling, and in the other two groups were with same volume solvent. Then the mice in LPS group and emodin+LPS group were stimulated with LPS (15mg/kg), and in the other two groups, meanwhile, received the same volume of normal saline. Mice were sacrificed 18h after LPS injection, and brain tissues and plasma samples were collected. Hematoxylin-eosin staining was performed to observe the pathological changes of brain tissues; the expression of S100-β protein in plasma was measured by ELISA to evaluate the degree of brain injury; the production of lactic acid (LA) in brain tissue was detected by colorimetric quantitative method to evaluate the degree of metabolic disorder in brain tissue; the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in plasma were measured by ELISA to evaluate the degree of systemic inflammatory response; the activity of neuro-specific enolase (NSE) was measured by ELISA to evaluate the degree of neuroinflammation; the activity of acetylcholinesterase (Ach-E) in brain tissue was measured by colorimetric quantitative method to evaluate the level of acetylcholine (Ach) in brain tissue. Results  Compared with normal control group, no obvious pathological damage of brain tissues was observed in emodin group, but obvious pathomorphological brain injury was observed in LPS group; While compared with LPS group, a significantly lighter degree of brain injury was found in emodin+LPS group; The levels of Ach-E and LA in brain tissue in LPS group [(1.09±0.10)U/mg and (0.35±0.03)mmol/g, respectively] markedly increased in comparison with those in normal control group [(0.84±0.09)U/mg and (0.16±0.03)mmol/g, respectively, P<0.05]; The plasma levels of S100β, IL-6, TNF-α and NSE in LPS group [(0.52±0.06)ng/ml, (4207.23±90.76)pg/ml, (355.62±6.88)pg/ml and (9.02±0.78)ng/ml, respectively] were also significantly higher than those in normal control group [(0.38±0.05)ng/ml, (501.60±74.18)pg/ml, (157.41±10.65) pg/ml and (5.41±0.89)ng/ml, respectively, P<0.05]; No statistically significant differences were observed in these indexes between emodin group and normal control group (P>0.05); Compared with LPS group, the plasma levels of S100β [(0.44±0.06) ng/ml], IL-6 [(1479.50±50.53)pg/ml], TNF-α [(213.48±9.19)pg/ml] and NSE [(6.74±1.12)ng/ml] in emodin+LPS group significantly reduced (P<0.05), and the levels in brain tissue of LA [(0.25±0.03)mmol/g protein] and Ach-E [(0.87±0.07)U/mg protein] also markedly down-regulated in emodin+LPS group (P<0.05). Conclusion  Emodin may have a protective effect on LPS-induced acute brain injury in mice, the mechanism is possibly activation of cholinergic anti-inflammatory pathway and inhibition of inflammatory response.

基金项目:
重庆市卫生计生委中医药科技项目(ZY201702083);重庆市渝中区科技计划研究基础与前沿项目(20170103)
作者简介:
董艳,硕士研究生。主要从事脑损伤的基础研究
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