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丹红注射液改善神经干细胞移植治疗脑缺血损伤效果的机制研究

王家传 余学问 徐华 李振国 徐洲稳 邵牧民

王家传, 余学问, 徐华, 等. 丹红注射液改善神经干细胞移植治疗脑缺血损伤效果的机制研究[J]. 器官移植, 2021, 12(4): 428-435. doi: 10.3969/j.issn.1674-7445.2021.04.009
引用本文: 王家传, 余学问, 徐华, 等. 丹红注射液改善神经干细胞移植治疗脑缺血损伤效果的机制研究[J]. 器官移植, 2021, 12(4): 428-435. doi: 10.3969/j.issn.1674-7445.2021.04.009
Wang Jiachuan, Yu Xuewen, Xu Hua, et al. Mechanism of Danhong injection in improving therapeutic effect of neural stem cell transplantation for cerebral ischemia injury[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 428-435. doi: 10.3969/j.issn.1674-7445.2021.04.009
Citation: Wang Jiachuan, Yu Xuewen, Xu Hua, et al. Mechanism of Danhong injection in improving therapeutic effect of neural stem cell transplantation for cerebral ischemia injury[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 428-435. doi: 10.3969/j.issn.1674-7445.2021.04.009

丹红注射液改善神经干细胞移植治疗脑缺血损伤效果的机制研究

doi: 10.3969/j.issn.1674-7445.2021.04.009
基金项目: 

国家自然科学基金面上项目 81774053

深圳市科技计划项目 JCYJ20170307155449972

详细信息
    通讯作者:

    王家传,男,1973年生,医学博士,博士后,副研究员,研究方向为干细胞移植与神经损伤修复,Email:jcwang0000@126.com

  • 中图分类号: R617, R28, R743.3

Mechanism of Danhong injection in improving therapeutic effect of neural stem cell transplantation for cerebral ischemia injury

More Information
  • 摘要:   目的  探讨丹红注射液能否通过调控核因子E2相关因子2(Nrf2)信号通路增强神经干细胞(NSC)移植修复脑缺血损伤的治疗效果。  方法  40只雄性SD大鼠随机分为NSC移植治疗组(NSC组)、丹红注射液组(DH组)、NSC+丹红注射液组(N+D组)、NSC+丹红注射液组+ML385组(N+D+M组)和PBS对照组(PBS组),每组8只。所有大鼠均采用大脑中动脉栓塞法建立脑缺血模型,栓塞1.5 h后进行再灌注。再灌注后3 d对各组大鼠进行相应处理。在NSC移植术前和术后1、2、4周进行神经功能评分。术后4周后处死大鼠,检测氧化应激相关指标,并用免疫荧光染色检测神经元特异核蛋白(NeuN)和血管性血友病因子(vWF)的表达情况。  结果  在NSC移植术前,各组大鼠的神经功能评分比较,差异无统计学意义(P > 0.05)。术后1、2、4周时,NSC组、DH组和N+D组大鼠的神经功能评分较PBS组和N+D+M组均降低(均为P < 0.05)。与PBS组和N+D+M组比较,NSC组、DH组和N+D组的丙二醛(MDA)水平均降低,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPX)水平均升高(均为P < 0.05);N+D+M组的GPX水平较PBS组降低(P < 0.05)。免疫荧光染色结果显示,移植到大鼠脑内的NSC能够迁移至脑梗死周边区域并存活,并表达神经元标志物NeuN和新生血管标志物vWF,而N+D+M组的NSC存活数量较其他组明显减少。  结论  丹红注射液可能通过调控Nrf2信号通路改善干细胞移植微环境,增加移植干细胞的存活率,提升NSC移植治疗脑缺血损伤效果。

     

  • 图  1  GPF阳性NSC球的显微镜下表现

    注:A、B图示第1代NSC球,C、D图示第5代NSC球; A、C图为光学显微镜下表现(×200),B、D图为荧光倒置显微镜下表现(免疫荧光,×200)。

    Figure  1.  The findings of GPF positive NSC sphere under microscope

    图  2  各组大鼠NSC移植术前、术后神经功能评分比较

    注:与PBS组比较,aP < 0.05;与N+D+M组比较,bP < 0.05。

    Figure  2.  Comparison of nerve function scores of rats before and after NSC transplantation amongeach group

    图  3  各组大鼠NSC移植术前、术后氧化应激相关指标比较

    注:与PBS组比较,aP < 0.05;与N+D+M组比较,bP < 0.05。

    Figure  3.  Comparison of oxidative stress related indexes of rats before and after NSC transplantation among each group

    图  4  NSC移植术后4周大鼠脑内NSC的存活和分布情况(免疫荧光,×200)

    注:A图为神经元标志物NeuN的免疫荧光染色; B图为新生血管标志物vWF的免疫荧光染色。

    Figure  4.  Survival and distribution of NSC in rat brain at 4 weeks after NSC transplantation

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出版历程
  • 收稿日期:  2021-04-30
  • 网络出版日期:  2021-07-13
  • 刊出日期:  2021-07-15

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