目的 研究玛咖酰胺B(Macamide B)对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)的新生小鼠神经元中颗粒蛋白前体(Progranulin,PGRN)及糖氧剥夺(oxygen-glucose deprivation,OGD)后的小鼠海马神经元细胞系(HT22)中PGRN表达的影响,探究Macamide B在新生小鼠HIBD后发挥神经保护作用的机制。 方法 建立HIBD小鼠模型,将出生后7 d的C57小鼠随机分为Sham组、HIBD组和Macamide B组;HT22细胞培养并制备OGD细胞模型,分为Control组、OGD组和Macamide B组。通过免疫荧光、Western blot检测小鼠神经元或HT22细胞中PGRN的表达。 结果 体内实验显示,与Sham组相比,HIBD组小鼠神经元中PGRN表达降低;与HIBD组相比,Macamide B组小鼠神经元中PGRN表达升高。在体外,与Control组相比,OGD组HT22细胞中PGRN表达降低;与OGD组相比,Macamide B组HT22细胞中PGRN表达显著升高。 结论 Macamide B可能通过促进PGRN表达对HIBD新生小鼠发挥神经保护作用。
Abstract
Objective To investigate the effect of Macamide B on the expression of progranulin (PGRN) in neurons of neonatal mice with hypoxic-ischemic brain damage (HIBD) and HT22 mouse hippocampal neuron cell line after oxygen-glucose deprivation (OGD) and explore the mechanism of the neuroprotective effect of Macamide B after HIBD in neonatal mice. Methods The HIBD model of C57 mice was established after 7 days of birth and the mice were divided into Sham group, HIBD group and Macamide B group. HT22 cells were cultured, then the OGD model of HT22 cells was established, and the cells were divided into Control group, OGD group and Macamide B group. The expression of PGRN in mouse neurons or HT22 cells was detected by immunofluorescence staining and Western blot. Results In vivo experiments showed that compared with Sham group, the expression of PGRN in mice neurons of HIBD group was reduced. Compared with HIBD group, the expression of PGRN in neurons of Macamide B group was increased. In vitro, compared with Control group, the expression of PGRN in HT22 cells of OGD group was decreased. Compared with OGD group, the expression of PGRN in HT22 cells of Macamide B group rose significantly. Conclusions Macamide B may play a neuroprotective role in HIBD neonatal mice by promoting the expression of PGRN.
关键词
缺氧缺血性脑损伤;  /
  /
Macamide B;  /
  /
神经保护;  /
  /
PGRN
Key words
Hypoxic-ischemic brain damage;  /
  /
Macamide B;  /
  /
Neuroprotection;  /
  /
PGRN
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Narayanamurthy R, Yang JL J, Yager JY, et al. Drug delivery platforms for neonatal brain injury[J]. J Control Release, 2021, 330(2): 765-787. DOI: 10.1016/j.jconrel.2020.12.056.
[2] Zhu JJ, Yu BY, Huang XK, et al. Neferine protects against hypoxic-ischemic brain damage in neonatal rats by suppressing NLRP3-mediated inflammasome activation[J]. Oxid Med Cell Longev, 2021, 2021(5): 6654954. DOI: 10.1155/2021/6654954.
[3] Kim BH, Jeziorek M, Kanal HD, et al. Moderately inducing autophagy reduces tertiary brain injury after perinatal hypoxia-ischemia[J]. Cells, 2021, 10(4): 898. DOI: 10.3390/cells10040898.
[4] 朱渝, 魏静, 吴鹏程, 等. 山莨菪碱缓解幼龄鼠缺氧缺血性脑组织形态和功能损伤[J]. 中国临床解剖学杂志, 2021, 39(5): 557-562, 568. DOI: 10.13418/j.issn.1001-165x.2021.05.011.
[5] Zhou Y, Li P, Brantner A, et al. Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients[J]. Sci Rep, 2017, 7: 44660. DOI: 10.1038/srep44660.
[6] Zhou Y, Wang H, Guo F, et al. Integrated proteomics and lipidomics investigation of the mechanism underlying the neuroprotective effect of N-benzylhexadecanamide[J]. Molecules, 2018, 23(11): 2929. DOI: 10.3390/molecules23112929.
[7] Yang X, Wang M, Zhou Q, et al. Macamide B pretreatment attenuates neonatal hypoxic-ischemic brain damage of mice induced apoptosis and regulates autophagy via the PI3K/AKT signaling pathway[J]. Mol Neurobiol, 2022, 59(5): 2776-2798. DOI: 10.1007/s12035-022-02751-4.
[8] Lan J, Hu Y, Wang X, et al. Abnormal spatiotemporal expression pattern of progranulin and neurodevelopment impairment in VPA-induced ASD rat model[J]. Neuropharmacology, 2021, 196(2021): 108689. DOI: 10.1016/j.neuropharm.2021.108689.
[9] 张万平, 秦艳, 张海鹰, 等. 七氟醚对脑缺血再灌注损伤大鼠认知功能及海马S100β及PGRN表达的影响[J]. 现代生物医学进展, 2021, 21(17): 3222-3226. DOI: 10.13241/j.cnki.pmb.2021.17.005.
[10]Wang L, Chen J, Hu Y, et al. Progranulin improves neural development via the PI3K/Akt/GSK-3β pathway in the cerebellum of a VPA-induced rat model of ASD[J]. Transl Psychiatry, 2022, 12(1): 114. DOI: 10.1038/s41398-022-01875-4.
[11]Altmann C, Hardt S, Fischer C, et al. Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: role of autophagy[J]. Neurobiol Dis, 2016, 96: 294-311. DOI: 10.1016/j.nbd.2016.09.010.
[12]Chen SX, Li KK, Pubu D, et al. Optimization of ultrasound-assisted extraction, HPLC and UHPLC-ESI-Q-TOF-MS/MS analysis of main macamides and macaenes from maca (cultivars of lepidium meyenii walp)[J]. Molecules, 2017, 22(12): 2196. DOI: 10.3390/molecules221 22196.
[14]Doke M, Matsuwaki T, Yamanouchi K, et al. Lack of estrogen receptor α in astrocytes of progranulin-deficient mice[J]. J Reprod Dev, 2016, 62(6): 547-551. DOI: 10.1262/jrd.2016-067.
[15]Wang Y, Wang X, Li Y, et al. Regulation of progranulin expression and location by sortilin in oxygen-glucose deprivation/reoxygenation injury[J]. Neurosci Lett,2020, 738: 135394. DOI: 10.1016/j.neulet. 2020. 135394.
基金
广东省中医药局科研项目(20212103);广东省医学科学技术研究基金(A2021466);广东普通高校科研项目(2021KQNCX033);国家青年自然科学基金项目(81901524);广东省医学科技研究基金项目(A2020252);广东省自然科学基金(2021A1515011525)