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首页 > 过刊浏览>2023年第33卷第8期 >114-121. DOI:10. 3969 / j.issn.1671-7856. 2023. 08. 015
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Penetratin 复合神经生长因子治疗中度创伤性颅脑损伤小鼠
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1.安徽医科大学基础医学院,合肥 230032;2.军事科学院军事医学研究院军事认知与脑科学研究所,北京 100850

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R-33


Treatment of moderate traumatic brain injury in mice by coadministration of nerve growth factor and penetratin
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Affiliation:

1. School of Basic Medicine, Anhui Medical University, Hefei 230032, China.2. Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850

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    摘要:

    目的 探讨penetratin 介导神经生长因子(NGF)对中度创伤性颅脑损伤(TBI)小鼠的治疗作用。 方法 首先在细胞水平利用细胞免疫荧光法评估不同细胞渗透肽(CPP)复合NGF 蛋白的穿膜效果,明确最佳的复合比例。随后在构建的中度TBI 小鼠模型上分析给药后各组小鼠的行为学变化:利用Morris 水迷宫实验检测小鼠的空间记忆功能,转棒实验评估小鼠的协调运动能力。采用免疫组化染色法观察脑组织GFAP、NeuN 蛋白的表达情况。 结果 体外细胞免疫荧光实验结果显示,NGF/ penetratin 组细胞内NGF 蛋白含量显著高于其他组,且在penetratin 与NGF 的摩尔比为20 ∶ 1 时荧光强度最高。动物实验结果显示,NGF/ penetratin 治疗组小鼠的协调运动功能、空间记忆能力以及脑组织内NeuN 蛋白表达水平均显著高于TBI 组与NGF 组小鼠,其脑组织内GFAP 蛋白表达水平显著低于TBI 组以及NGF 组小鼠(P<0. 05)。 结论 Penetratin 作为一种药物递送载体可促进NGF 通过血脑屏障(BBB)进入受损脑组织内,对中度TBI 小鼠具有较好的治疗作用。

    Abstract:

    Objective To evaluate the therapeutic potential of nerve growth factor (NGF) with penetratin on moderate traumatic brain injury (TBI). Methods The effect of various cell-penetrating peptides combined with NGF on membrane penetration was analyzed by fluorescence immunocytochemistry in cells in vitro, and the optimal molar ratio was selected. Subsequently, rotarod performance and Morris water maze tests were performed to analyze behavioral changes of the moderate TBI mouse model in each group after administration, including coordinative motor ability and the spatial memory function. GFAP and NeuN protein expression was observed by immunohistochemistry. Results Fluorescence immunocytochemistry showed that the content of NGF protein in cells of the NGF/ penetratin group was significantly higher than that in the other groups, and the fluorescence intensity was the highest at a molar ratio of 20 ∶ 1 (penetratin:NGF). Behavioral test showed that the coordination motor function and spatial memory ability of mice in the NGF/ penetratin group were significantly better than those in TBI and NGF groups. Additionally, NeuN protein expression in brain tissue of mice in the NGF/ penetratin group were also significantly higher than that in TBI and NGF groups, while GFAP protein expression in brain tissue was significantly lower than that in the two groups (P<0. 05). Conclusions Penetratin as a drug delivery carrier promotes NGF to cross the blood-brain barrier and enter damaged brain tissue, which has a good therapeutic effect on moderate TBI mice.

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尤丽丽,付文亮,裴 洁,俞昶乐,邢微微,蔡贵玲,张 超,徐东刚. Penetratin 复合神经生长因子治疗中度创伤性颅脑损伤小鼠[J].中国比较医学杂志,2023,33(8):114~121.

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  • 收稿日期:2023-02-21
  • 在线发布日期: 2023-11-09
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