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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (4): 22-25.doi: 10.6040/j.issn.1671-7554.0.2014.771

• 基础医学 • 上一篇    下一篇

MiR-29c在大鼠蛛网膜下腔出血后抑制柔脑膜纤维化的实验研究

成利1, 张传斌1, 李猛2, 张玉震2, 孙金龙2   

  1. 1. 山东大学医学院, 山东 济南 250012;
    2. 山东大学附属千佛山医院神经外科, 山东 济南 250014
  • 收稿日期:2014-10-31 修回日期:2015-03-09 出版日期:2015-04-10 发布日期:2015-04-10
  • 通讯作者: 孙金龙.E-mail:13805311206@139.com E-mail:13805311206@139.com
  • 基金资助:
    山东省科技发展计划(2010GSF10211)

Anti-fibrosis role of miR-29c in rat leptomeninge after experimental subarachnoid hemorrhage

CHENG Li1, ZHANG Chuanbin1, LI Meng2, ZHANG Yuzhen2, SUN Jinlong2   

  1. 1. School of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Neurosurgery, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2014-10-31 Revised:2015-03-09 Online:2015-04-10 Published:2015-04-10

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摘要： 目的 探讨miR-29c在蛛网膜下腔出血(SAH)后柔脑膜纤维化过程中的作用.方法 选用健康雄性SD大鼠26只按随机数字表法分为假手术组(6只)、空白慢病毒组(8只)、LV-rno-miRNA-29c组(12只).侧脑室分别注入5 μL生理盐水、空白慢病毒、LV-rno-miRNA-29c,注射1周后,通过枕大池二次注血法建立蛛网膜下腔出血模型.造模21 d后处死大鼠,采用Realtime PCR法检测柔脑膜内转化生长因子β1(TGF-β1)及miR-29c表达量,酶联免疫吸附法(ELISA)检测脑脊液(CSF)中Ⅰ型胶原前端肽(PICP)含量,柔脑膜Masson染色观察柔脑膜胶原纤维.结果 SAH后柔脑膜中TGF-β1表达升高,miR-29c表达下调;上调miR-29c能显著抑制脑脊液中PICP及柔脑膜中胶原表达.结论 维持miR-29c高表达可抑制SAH后柔脑膜胶原合成,从而治疗柔脑膜纤维化.

关键词: 脑积水, 1, 变应性疾病, 柔脑膜纤维化, 蛛网膜下腔出血, 转化生长因子&beta, 微RNAs, 变应原, 皮肤点刺试验

Abstract: Objective To explore the role of miR-29c in rat leptomeningeal fibrosis after subarachnoid hemorrhage (SAH). Methods A total of 26 healthy Sprague-Dawley (SD) rats were randomly divided into sham group (n=6), empty lentiviral group (n=8), and LV-rno-miRNA-29c group (n=12). 5 μL saline, empty lentivirus and LV-rno-miRNA-29c were respectively injected into the lateral cerebral ventricle of rats in each group. The SAH models were induced by injecting autologous blood twice into the cisterna magna, and 21 days later the rats were killed. Realtime PCR was used to detect the expressions of TGF-β1 and miR-29c. Masson staining was performed to observe collagen fiber. ELISA was adopted to measure the level of PICP in CSF. Results Increased TGF-β1 and decreased miR-29c were detected. The upregulation of miR-29c could significantly reduce the expressions of PICP in CSF and collagen in leptomeninge. Conclusion High expression of miR-29c may have potential therapeutic effects for leptomeningeal fibrosis by inhibiting collagen synthesis after SAH.

Key words: Allergic diseases, Allergens, Subarachnoid hemorrhage, Hydrocephalus, Leptomeningeal fibrosis, Transforming growth factor β1, microRNAs, Skin prick test

中图分类号: 

  • R651.1
[1] Sajanti J, Heikkinen E, Majamaa K. Transient increase in procollagen propeptides in the CSF after subarachnoid hemorrhage[J]. Neurology, 2000, 55(3): 359-363.
[2] Zhang Y, Huang XR, Wei LH, et al. MiR-29b as a therapeutic agent for angiotensin II-induced cardiac fibrosis by targeting TGF-beta/Smad3 signaling[J]. Mol Ther, 2014, 22(5): 974-985.
[3] Tiao MM, Wang FS, Huang LT, et al. MicroRNA-29a protects against acute liver injury in a mouse model of obstructive jaundice via inhibition of the extrinsic apoptosis pathway[J]. Apoptosis, 2014, 19(1): 30-41.
[4] Yang T, Liang Y, Lin Q, et al. MiR-29 mediates TGFbeta1-induced extracellular matrix synthesis through activation of PI3K-AKT pathway in human lung fibroblasts[J]. J Cell Biochem, 2013, 114(6): 1336-1342.
[5] Ramdas V, Mcbride M, Denby L, et al. Canonical transforming growth factor-beta signaling regulates disintegrin metalloprotease expression in experimental renal fibrosis via miR-29[J]. Am J Pathol, 2013, 183(6): 1885-1896.
[6] 张天一,刘飞,廖达光,等. 实验性蛛网膜下腔出血后柔脑膜纤维化的研究[J]. 中风与神经疾病杂志, 2008, 25(3): 277-280. ZHANG Tianyi, LIU Fei, LIAO Daguang, et al. Index of leptomeningeal fibrosis after experimental subarachnoid hemorrhage[J]. Chinese Journal of Critical Care Medicine, 2008, 25(3): 277-280.
[7] Flood C, Akinwunmi J, Lagord C, et al. Transforming growth factor-beta1 in the cerebrospinal fluid of patients with subarachnoid hemorrhage: titers derived from exogenous and endogenous sources[J]. J Cereb Blood Flow Metab, 2001, 21(2): 157-162.
[8] Moinuddin SM, Tada T. Study of cerebrospinal fluid flow dynamics in TGF-beta1 induced chronic hydrocephalic mice[J]. Neurol Res, 2000, 22(2): 215-222.
[9] Botfield H, Gonzalez AM, Abdullah O, et al. Decorin prevents the development of juvenile communicating hydrocephalus[J]. Brain, 2013, 136(Pt 9): 2842-2858.
[10] Lee P, Monaco ER, Friedlander RM. Blocking TGF-beta activity and associated inflammation may halt hydrocephalus[J]. Neurosurgery, 2013, 73(6): N13-N14.
[11] Makwana M, Jones LL, Cuthill D, et al. Endogenous transforming growth factor beta 1 suppresses inflammation and promotes survival in adult CNS[J]. J Neurosci, 2007, 27(42): 11201-11213.
[12] Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2): 281-297.
[13] van Rooij E, Sutherland LB, Thatcher JE, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis[J]. Proc Natl Acad Sci U S A, 2008, 105(35): 13027-13032.
[14] Pandit KV, Milosevic J, Kaminski N. MicroRNAs in idiopathic pulmonary fibrosis[J]. Transl Res, 2011, 157(4): 191-199.
[15] Maurer B, Stanczyk J, Jungel A, et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis[J]. Arthritis Rheum, 2010, 62(6): 1733-1743.
[16] Bian EB, Li J, Zhao B. MiR-29, a potential therapeutic target for liver fibrosis[J]. Gene, 2014, 544(2): 259-260.
[17] Qin W, Chung AC, Huang XR, et al. TGF-beta/Smad3 signaling promotes renal fibrosis by inhibiting miR-29[J]. J Am Soc Nephrol, 2011, 22(8): 1462-1474.
[18] Wang B, Komers R, Carew R, et al. Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis[J]. J Am Soc Nephrol, 2012, 23(2): 252-265.
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