依达拉奉对缺氧缺血性脑病新生大鼠脑水肿及CD163/ HO-1 信号通路的影响
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(贵州省遵义市第一人民医院新生儿科,贵州遵义 563002)

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R-33

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Influence of edaravone on cerebral edema in neonatal rats with hypoxic-ischemic encephalopathy and on CD163/ HO-1 signaling pathway
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(Department of Neonatology,the First People’s Hospital of Zunyi, Zunyi 563002,China)

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    摘要:

    目的 探究依达拉奉对缺氧缺血性脑病(HIE)新生大鼠脑水肿及CD163/ HO-1 信号通路的影响?方法 7 日龄SD 新生大鼠120 只,其中90 只双结扎左颈总动脉并缺氧制作缺氧缺血性脑损伤(hypoxic ischemicbrain damage,HIBD)模型,并随机分为模型组?依达拉奉组,另外30 只仅穿线不结扎不缺氧作为假手术组?依达拉奉组在造模后立即腹腔注射依达拉奉2 mg/ kg,每日1 次,连续5 d;模型组和假手术组分别在同一时间给予腹腔注射等量生理盐水?术后注意观察各组SD 新生大鼠的生物学行为?造模后24 h,TTC 染色观察各组SD 新生大鼠脑组织形态?造模后在6 h?12 h?24 h?2 d?3 d?5 d 分别检测各组SD 新生大鼠脑组织含水量变化;荧光定量PCR(qRT-PCR)技术检测CD163?HO-1 mRNA 表达水平; Western blot 技术检测CD163?HO-1 蛋白表达水平?结果 术后90 只SD 新生大鼠出现嗜睡?精神萎靡?抽搐等症状,依达拉奉治疗后症状较模型组明显减轻,3 d 内症状改善?TTC 染色发现造模后24 h 模型组新生大鼠左脑半球出现水肿?颜色苍白,体积比右半球稍大,依达拉奉治疗后脑组织损伤程度显著降低?模型组?依达拉奉组新生大鼠大脑左半球梗死面积均显著大于假手术组( P <0. 05),依达拉奉治疗后脑梗死面积显著小于模型组( P <0. 05)?脑组织含水量检测结果显示:造模后6 h,模型组?依达拉奉组新生大鼠脑组织含水量均显著高于假手术组( P <0. 05),2 d 时脑含水量最高?依达拉奉治疗后新生大鼠脑组织含水量明显低于模型组( P <0. 05)?qRT-PCR 和Western blot 结果显示,与假手术组相比,模型组?依达拉奉组新生大鼠脑组织CD163?HO-1 mRNA 和蛋白表达水平均显著升高( P <0. 05),依达拉奉治疗后新生大鼠CD163?HO-1 mRNA和蛋白表达水平显著高于模型组( P <0. 05)?结论 依达拉奉能明显减轻HIBD 新生大鼠脑水肿?脑梗死程度,其机制可能与CD163/ HO-1 信号通路受到活化有关?

    Abstract:

    Objective To explore the influence of edaravone on cerebral edema in neonatal rats with hypoxicischemicencephalopathy (HIE) and on the CD163/ HO-1 signaling pathway. Methods A total of 120 SD neonatal rats (7days old) were included here, 90 of which underwent double ligation of the proximal and distal ends the left commoncarotid artery to establish a hypoxic-ischemic brain damage (HIBD) model. After ligation and hypoxia the rats were thendivided into a model group and an edaravone group. The remaining 30 rats had only separated the common carotid arterywithout ligation as a sham operation group. The rats in the edaravone group were immediately intraperitoneally injected with2 mg/ kg edaravone after model establishment, once a day for 5 consecutive days. The model group and the sham operationgroup were given the same amount of saline intraperitoneally at the same time. After operation, the biological behaviors ofthe neonatal rats were observed. After modeling for 24 h,the morphology of brain tissue in neonatal rats was observed byTTC staining. Changes of the water content in brain tissue of neonatal SD rats were detected at 6, 12, and 24 h, and 2, 3,and 5 days after model establishment. CD163 and HO-1 mRNA expression levels were determined by quantitativefluorescence PCR (qRT-PCR). CD163 and HO-1 protein expression levels were tested using western blotting. Results After operation, 90 neonatal rats showed lethargy, malaise, and convulsions. Those symptoms were clearly alleviated aftertreatment with edaravone compared with those in the model group, and improved within 3 days. At 24 h after modelestablishment, TTC staining showed that the left hemisphere was edematous and had a pale color in the model group, andalso had a slightly larger volume than the right hemisphere. The degree of injury of brain tissue significantly decreased afteredaravone treatment. The infarct size in the left hemisphere of the rats in the model group and the edaravone group wassignificantly greater than that in the sham operation group ( P < 0. 05), and the infarct size in the edaravone-treated groupwas significantly smaller than that in the model group ( P < 0. 05). At 6 h after modeling, water contents of brain tissue inthe model group and edaravone group were significantly higher than that in the sham operation group ( P < 0. 05), and brainwater content was the highest at 2 days. The water content in brain tissue of neonatal rats treated with edaravone wassignificantly lower than that in the model group ( P < 0. 05). qRT-PCR and western blotting showed that CD163 and HO-1mRNA/ protein expression levels in brain tissue of neonatal rats in the model group and edaravone group were significantlyincreased compared with those in the sham operation group ( P < 0. 05). CD163 and HO-1 mRNA/ protein expression levelsin neonatal rats were significantly higher than those in the model group after edaravone treatment ( P < 0. 05). Conclusions Edaravone can clearly reduce the degrees of cerebral edema and cerebral infarction in neonatal rats with HIBD. The mechanism behind this may be related to activation of the CD163/ HO-1 signaling pathway.

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韩遵华,段淼,李清香.依达拉奉对缺氧缺血性脑病新生大鼠脑水肿及CD163/ HO-1 信号通路的影响[J].中国比较医学杂志,2019,29(4):34~40.

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  • 收稿日期:2018-09-30
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  • 在线发布日期: 2019-05-10
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