胍基丁胺通过调节 Nrf2 / HO-1 信号通路减轻丙泊酚诱导的新生大鼠的神经毒性
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1.南阳市第一人民医院儿一科,河南 南阳 473000; 2.新乡医学院第一附属医院 内分泌二病区,河南 新乡 453100

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R-33

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Agmatine attenuates propofol-induced neurotoxicity in newborn rats by regulating the Nrf2 / HO-1 signaling pathway
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1. Department of Pediatrics, Nanyang First People’s Hospital, Nanyang 473000, China. 2. the Second Department of Endocrinology, First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100

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    摘要:

    目的 本文旨在探讨胍基丁胺对丙泊酚诱导的新生大鼠的神经毒性的影响。 方法 通过腹腔注射丙泊酚诱导神经损伤模型将大鼠分为 5 组:Control 组、Propofol 组、Propofol +Agmatine 1. 25 mg / kg 组、Propofol + Agmatine 2. 5 mg / kg 组和 Propofol+Agmatine 5 mg / kg 组。 跳台实验检测犯错次数,2,3,5-三苯基氯化四氮唑法检测脑含水率、脑指数,Longa 法评价神经功能缺陷评分、姿势反射评分 HE 染色检测海马区病理损伤程度,Nissl 染色检测海马区组织凋亡,蛋白免疫印迹检测各组大鼠脑组织 BDNF、NGF、Bax、Bcl-2、Nrf2、p-Nrf2、HO-1 蛋白表达水平。 结果 结果表明,与 Control 组相比较,Propofol 组犯错次数显著升高(P<0. 05),脑含水率、脑指数显著升高(P< 0. 05),神经功能缺陷评分、姿势反射评分显著升高(P<0. 05),呈现明显病理损伤,BDNF、NGF 蛋白水平显著降低 (P<0. 05),Nissl 小体数目明显减少,Bax / Bcl-2 比值显著升高(P<0. 05),p-Nrf2 / Nrf2 比值和 HO-1 蛋白水平显著降 低(P<0. 05)。 与 Propofol 组相比较,Propofol+Agmatine 2. 5、5 mg / kg 组犯错次数显著降低(P<0. 05),脑含水率、脑指数显著降低(P<0. 05),神经功能缺陷评分、姿势反射评分显著降低(P<0. 05),病理损伤程度明显改善,BDNF、 NGF 蛋白水平显著升高(P<0. 05),Nissl 小体数目明显增多,Bax / Bcl-2 比值显著降低(P<0. 05),p-Nrf2 / Nrf2 比值和 HO-1 蛋白水平显著升高(P<0. 05)。 结论 胍基丁胺通过调节 Nrf2 / HO-1 信号通路减轻丙泊酚诱导的新生大鼠的神经毒性。

    Abstract:

    Objective To investigate the effects of agmatine on Propofol-induced neurotoxicity in newborn rats. Methods Rats were divided into five groups for follow-up experiments: Control, Propofol, Propofol + 1 mg / kg Agmatine, Propofol + 2. 5 mg / kg Agmatine, and Propofol + 5 mg / kg Agmatine. The number of errors was detected in a platform experiment, while brain moisture content and brain index were determined by a 2, 3, 5-triphenyl tetrazolium chloride method. The Longa method was used to evaluate neural functional defect and postural reflex scores. HE staining was used to detect the degree of pathological damage in the hippocampus. Apoptosis of hippocampal tissue was detected by Nissl staining. Western blot was used to detect protein expression levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Bax, Bcl-2, Nrf2, p-Nrf2, and heme oxygenase 1 (HO-1). Results Compared with the Control group, the Propofol group exhibited significant increases in the number of platform errors (P<0. 05), brain water content and cerebral index (P<0. 05), neural function defect scores, and posture reflex scores (P< 0. 05), as well as obvious pathological damage. Moreover, the Propofol group exhibited significantly reduced expression of BDNF, NGF, and HO-1 proteins (P<0. 05), p-Nrf2 / Nrf2 ratio (P<0. 05), and numbers of Nissl bodies (P<0. 05), but a significantly higher Bax / Bcl-2 ratio (P<0. 05). Compared with the Propofol group, Propofol+Agmatine groups (2. 5 and 5 mg / kg) exhibited significantly decreased numbers of platform errors ( P< 0. 05), brain water content and cerebral index ( P< 0. 05), neurologic deficit scores (P<0. 05), and posture reflex scores (P<0. 05). Moreover, the degree of pathological damage was significantly improved in Propofol+Agmatine groups, which exhibited significantly increased BDNF and NGF protein expression (P<0. 05), and numbers of Nissl bodies (P<0. 05), and a significantly decreased Bax / Bcl-2 ratio (P<0. 05;. p-Nrf2 / Nrf2 ratio and HO-1 protein expression were also significantly increased ( P<<0.05). Conclusions Agmatine attenuates Propofol-induced neurotoxicity in newborn rats by regulating the Nrf2 / HO-1 signaling pathway.

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张少华,张彦芳,曹 萌,李 燕,廖立夏,王贝贝.胍基丁胺通过调节 Nrf2 / HO-1 信号通路减轻丙泊酚诱导的新生大鼠的神经毒性[J].中国比较医学杂志,2020,30(12):17~22,119.

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  • 收稿日期:2020-05-07
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  • 在线发布日期: 2021-02-10
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