目的 探讨血小板衍生生长因子受体α(platelet-derived growth factor receptor alpha,PDGFRα)在小鼠黑质纹状体损伤周边的经时表达和定位。 方法 取8周龄BALB/c小鼠,按文献制备小鼠黑质纹状体通路损伤模型,分别于术后第1、4、7、14 d取损伤脑组织(延及损伤部位前后2 mm)进行检测。应用免疫组织化学染色和Western blot检测p-PDGFRα蛋白的经时表达;采用免疫荧光双重染色检测p-PDGFRα的定位表达。 结果 免疫组化和Western blot检测均显示,损伤后4 d p-PDGFRα表达至高峰水平,免疫荧光双重染色结果显示其表达在星形胶质细胞,小胶质细胞,少突胶质细胞祖细胞和粒细胞上。 结论 脑损伤可以使PDGFRα活化并表达于损伤周围,活化的PDGFRα可能与星形胶质细胞,小胶质细胞,少突胶质细胞祖细胞和粒细胞的增殖有关。
Abstract
Objective To investigate the expression and localization of platelet-derived growth factor receptor alpha (PDGFRα) at different stages after substantia nigra striatum injury in mice. Methods The substantia nigra striatum pathway was unilaterally transected in 8 weeks old BALB/c mice. According to the method of Baidan, brain tissues of 2 mm around the injury brain were examined on the 1st, 4th, 7th and 14th day after operation. The expression of p-PDGFR alpha protein was detected by immunohistochemical staining and Western blot. Immunofluorescence double staining was used to detect the localized expression of p-PDGFR alpha. Results Immunohistochemical staining and Western blot showed that the expression of p-PDGFR alpha reached its peak level 4 days after injury. Double immunofluorescence staining showed that p-PDGFR alpha was expressed in astrocytes, microglia, leukocytes and oligodendrocytes. Conclusions Brain injury can activate PDGFR alpha and express around the injury. Activated PDGFR alpha may be related to the proliferation of astrocytes, microglia, leukocytes and oligodendrocytes.
关键词
血小板衍生生长因子受体 /
脑损伤 /
星形胶质细胞 /
小胶质细胞 /
少突胶质细胞祖细胞 /
粒细胞
Key words
PDGFR /
Brain injury; Astrocytes; Microglia /
Oligodendrocytes /
Leukocytes
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Spencer T, Domeniconi M, Cao ZX, et al. New roles for old proteins in adult CNS axonal regeneration[J]. Curr Opin Neurobiol, 2003, 13(1): 133-139. DOI: 10.1016/s0959-4388(03)00012-6.
[2] Mocchetti I, Wrathall JR. Neurotrophic factors in central nervous system trauma[J]. J Neurotrauma, 1995, 12(5): 853-870. DOI: 0.1089/neu.1995.12.853.
[3] Kimura-Kuroda J, Teng X, Komura Y, et al. An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury[J]. Mol Cell Neurosci, 2010, 43(2): 177-187. DOI: 10.1016/j.mcn.2009.10.008.
[4] Schachtrup C, Ryu JK, Helmrick MJ, et al. Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-beta after vascular damage[J]. J Neurosci, 2010, 30(17): 5843-5854. DOI: 10.1523/JNEUROSCI.0137-10.2010.
[5] Hayashi Y, Nomura M, Yamagishi S, et al. Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes[J]. Glia, 1997, 19(1): 13-26. PMID: 8989564.
[6] 白丹, 裴丹, 刘囡, 等. 降解纤维蛋白原可减少创伤性脑损伤后胶质瘢痕与纤维瘢痕的形成[J]. 解剖学报, 2014, 45(6): 729-734. DOI: 10.3969/j.issn.0529-1356.2014.06.001.
[7] Strbian D, Durukan A, Tatlisumak T. Rodent models of hemorrhagic stroke[J]. Curr Pharm Des, 2008, 14(4): 352-358. DOI: 10.2174/138161208783497723.
[8] Wang Z, Kong D, Banerjee S, et al. Down-regulation of platelet-derived growth factor-D inhibits cell growth and angiogenesis through inactivation of Notch-1 and nuclear factor-kappaB signaling[J]. Cancer Res, 2007, 67(23): 11377-11385. DOI: 10.1158/0008-5472.CAN-07-2803.
[9] Hoch RV, Soriano P. Roles of PDGF in animal development[J]. Development, 2003, 130(20): 4769-4784. DOI: 10.1242/dev.00721.
[10]Li R, Maminishkis A, Wang FE, et al. PDGF-C and -D induced proliferation/migration of human RPE is abolished by inflammatory cytokines[J]. Invest Ophthalmol Vis Sci, 2007, 48(12): 5722-5732. DOI: 10.1167/iovs.07-0327.
[11]Li X, Kumar A, Zhang F, et al. VEGF-independent angiogenic pathways induced by PDGF-C[J]. Oncotarget, 2010, 1(4): 309-314. DOI: 10.18632/oncotarget.141.
[12]Uutela M, Wirzenius M, Paavonen K, et al. PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis[J]. Blood, 2004, 104(10): 3198-3204. DOI: 10.1182/blood-2004-04-1485.
[13]Deuel TF, Senior RM, Huang JS, et al. Chemotaxis of monocytes and neutrophils to platelet-derived growth factor[J]. J Clin Invest, 1982, 69(64): 1046-1049. DOI: 10.1172/jci110509.
[14]Thommen R, Humar R, Misevic G, et al. PDGF-BB increases endothelial migration on cord movement during angiogenesis in vitor[J]. J Cell Biochem, 1997, 64(3): 403-413. PMID: 9057098.
[15] Kumagai S, Ohtani H, Nagai T, et al. Platelet-derived growth factor and its receptors are expressed in areas of both active inflammation and active fibrosis in inflammatory bowel disease[J]. Tohoku J Exp Med, 2001, 195(1): 21-33. DOI: 10.1620/tjem.195.21.
[16] Miyatake SI, Furuse M, Kawabata S, et al. Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases[J]. Neuro-oncology, 2013, 15(6): 650-655. DOI: 10.1093/neuonc/not020.
[17] Ungvari Z, Podlutsky A, Sosnowska D, et al. Ionizing radiation promotes the acquisition of a senescence-associated secretory phenotype and impairs angiogenic capacity in cerebromicrovascular endothelial cells: role of increased DNA damage and decreased DNA repair capacity in microvascular radiosensitivity[J]. J Gerontol Series A Biol Sci Med Sci, 2013, 68(12): 1443-1457. DOI: 10.1093/gerona/glt057.
基金
辽宁省教育厅科学技术研究项目青年项目(JYTQ N201716)