氢吗啡酮对脓毒性脑病大鼠的脑保护作用  

Protective effect of hydromorphone on the brain of rats with septic encephalopathy

作　　者：付磊[1] 代静静 王兆[1] FU Lei;DAI Jing-jing;WANG Zhao(Department of Intensive Care Unit,the First People's Hospital of Zunyi,Zunyi 563000,Guizhou Province,China)

机构地区：[1]遵义市第一人民医院重症医学科,贵州遵义563000

出　　处：《中国临床药理学杂志》2022年第21期2586-2590,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的基于核因子E2相关因子2/血红素氧合酶-1(Nrf2/HO-1)通信号通路探讨氢吗啡酮(HM)对脓毒性脑病(SE)大鼠的脑保护作用。方法选择清洁级(SPF)雌性SD大鼠60只,将其中20只大鼠分别假手术组、对照组(NC组),每组10只,均用等剂量的0.9%氯化钠处理,每天1次,持续3 d;而其余40只大鼠采用盲肠结扎穿孔术(CLP)建立脓毒症模型,并通过相关标准筛选SE模型,最终确定建模成功31只SE大鼠,分为模型组10例、实验组11例、二甲基亚砜组(DMSO组)10例,模型组用等剂量的0.9%氯化钠水溶液处理,每天1次,持续3 d,DMSO组腹腔注射2%DMSO 1 mL,实验组在造模前1 h腹腔注射尾静脉注射给予氢吗啡酮10 mg·kg。用苏木精-伊红(HE)染色观察各组大鼠脑组织结构排列及神经元存活情况,用双抗体夹心酶联免疫吸附法检测大鼠血浆中白细胞介素(IL)-1、IL-6、IL-10以及肿瘤坏死因子-α(TNF-α)水平,用蛋白质印迹法检测各组大鼠Nrf2、HO-1、BTB-CNC异体同源体1(Bach1)的表达情况。结果NC组、假手术组、模型组、DMSO组、HM组神经元存活率分别为(94.33±3.17)%,(92.83±4.28)%,(63.82±3.28)%,(82.17±5.04)%,(76.71±4.43)%,差异有统计学意义(P<0.05)。与对照组和假手术组相比,模型组、DMSO组、实验组大鼠TNF-α、IL-1、IL-6、IL-10以及Bach1表达均显著升高(P<0.05);与模型组相比,DMSO组、实验组上述指标数值显著降低(P<0.05)。对照组、假手术组、模型组、DMSO组、实验组的Nrf2相对表达量分别为0.75±0.04,0.79±0.08,0.29±0.03,0.46±0.06和0.60±0.06,HO-1相对表达量分别为0.70±0.05,0.65±0.07,0.26±0.03,0.37±0.06和0.51±0.06,Bach1相对表达量分别为0.45±0.04,0.46±0.04,0.97±0.12,0.58±0.05和0.73±0.07,模型组、DMSO组、实验组的上述指标与对照组和假手术组比较,差异均有统计学意义(均P<0.05),DMSO组、实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论氢吗啡酮预处理能够显�Objective To explore the brain protection effect of hydromorphone(HM)on septic encephalopathy(SE)rats based on the nuclear factor E2-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.Methods Sixty clean grade(SPF)female SD rats were selected,20 of which were divided into sham operation group and normal control group(NC group),10 rats in each group,treated with equal dose of 0.9%NaCl,once a day for 3 d;while the remaining 40 rats were established sepsis models by cecal ligation and puncture(CLP),and SE models were screened by relevantstandards,finally 31 SE rats were successfully modeled,were divided into model group 10 rats,experimental group 11rats,and dimethyl sulfoxide group(DMSO group)10 rats.Model group was treated with equal dose of 0.9% NaCl,once a day for 3 d,DMSO group was intraperitoneally injected with 2% DMSO 1 mL,experimental group wasintraperitoneally injected with HM 10 mg·kg^(-1)by tail vein injection at 1 h before modeling.Hematoxylin-eosin(HE)staining was used to observe the structural arrangement of rat brain tissues and neuron survival in each group.Double antibody sandwich enzyme-linked immunosorbent assay was used to detect interleukin(IL)-1,IL-6,IL-10 and tumor necrosis factor-α(TNF-α)in rat plasma.Western blot was used to detect the expression of Nrf2,HO-1,BTB-CNC allologous 1(Bach1)in each group of rats.Results The neuron survival rates of NC group,sham operation group,model group,DMSO group and experimental group were(94.33±3.17)%,(92.83±4.28)%,(63.82±3.28)%,(82.17±5.04)%,(76.71±4.43)%,respectively,the difference was statistically significant(P<0.05).Compared with NC group and sham operation group,TNF-α,IL-1,IL-6,IL-10 and the expressionof Bach1 in model group,DMSO group and experimental group were significantly increased(allP<0.05).Comparedwith model group,the values of the above indicators in DMSO group and experimental group were significantly lower(allP<0.05).The relative expression levels of Nrf2 in NC group,sham operation group,model group,DMSO groupand experim

关 键 词：脓毒性脑病 核因子E2相关因子2/血红素氧合酶-1通信号通路 氢吗啡酮 脑保护作用 

分 类 号：R971[医药卫生—药品]