期刊文献+

CpG-ODN对新生大鼠缺血/缺氧性脑损伤的保护作用研究 被引量:3

Protective effect of CpG-ODN conditioning on hypoxic/ischemic brain damage in neonatal rats
下载PDF
导出
摘要 目的探讨Toll样受体9(Toll-like receptor 9,TLR9)激动剂——含Cp G基序的寡核苷酸(Cp G-ODN)对新生大鼠缺血/缺氧性脑损伤的保护作用机制。方法 50只健康7日龄新生Wistar大鼠,♀♂不限,随机分为5组,假手术组、缺血/缺氧性脑损伤(HIBD)组、Cp G-ODN低剂量组(0.35m L·kg-1)、Cp G-ODN中剂量组(1.40 m L·kg-1)、Cp GODN高剂量组(5.60 m L·kg-1)。术后48 h对大鼠神经功能进行评分,光学显微镜下观察脑组织病理学改变。免疫印迹法检测缺血/缺氧侧脑组织中磷酸化p38 MAPK、TLR9表达,酶联免疫吸附法检测TNF-α的表达。结果 Cp G-ODN低、中剂量组较模型组神经行为学评分降低,病理学损伤减轻,而高剂量组较模型组神经行为学评分升高(P<0.05),病理学损伤加重;Western blot分析结果表明,缺血/缺氧侧脑组织中磷酸p38 MAPK、TLR9蛋白表达逐渐上调,TNF-α在脑组织中含量逐渐升高(P<0.05)。结论 TLR9激动剂Cp G-ODN低、中剂量可改善新生大鼠脑缺血/缺氧损伤神经行为学评分及神经系统功能,减轻新生大鼠缺血/缺氧性脑损伤,其机制可能是通过适度激活p38 MAPK信号通路,并分泌适量TNF-α发挥作用。 Aim To study the therapeutic effect of Cp G-ODN,an agonist of Toll-like receptor 9(TLR9),on hypoxic/ischemic encephapathy in neonatal rats and investigate the mechanisms.Methods Fifty healthy7-day-old neonatal Wistar rats(in either gender,weighing 12 ~ 17g) were randomly divided into sham operation group,HIBD group,and Cp G-ODN low group(0.35 m L·kg^-1),Cp G-ODN middle group(1.40 m L·kg^-1),Cp G-ODN high group(5.60 m L·kg^-1).The neurological function was scored after 48 h operation;ten rats of each group was executed respectively and brains tissue was taken;HE staining was used to observe the brain pathological changes.Western blot assay was used to detect the expressions of TLR9 and phosphor-p38 mitogen-activated protein kinases(p-p38MAPK),and enzyme linked immunosorbent assay(ELISA) method was adopted to detect TNF-α expression.Results The Cp G-ODN low,middle group were improved in impairment significantly compared with the HIBD group,and the brain pathological change was lessened,while the Cp G-ODN high group was impaired significantly compared with the HIBD group(P〈0.05),and brain pathological change was sharpened.Western blot showed the up-regulation in TLR9 and pp38 MAPK and a significant increase of the expression of TNF-α in the brain tissue in Cp G-ODN group with statistical difference in HIBD group and sham operation group(P〈0.05).Conclusions The neuro-behavioral score and nervous system function can be improved and the hypoxic/ischemic brain damage can be re-duced in neonatal rats in the Cp G-ODN low,middle group.The protective mechanisms may be suitably via activating p38 MAPK signaling pathway to promote p38 MAPK phosphory1ation and up-regulation of the expression of TNF-α in the brain tissue of rats.
出处 《中国药理学通报》 CAS CSCD 北大核心 2017年第7期956-961,共6页 Chinese Pharmacological Bulletin
基金 贵州省科技厅基金(2014-3)厅校联合项目[黔科合LG字(2011)006号] 贵州省科技计划项目[黔科合平台人才(2016)5625]
关键词 缺血/缺氧脑损伤 TNF-Α TLR9 CPG-ODN P38丝裂原活化蛋白激酶 hypoxic/ischemic brain damage cerebral TNF-α TLR9 CpG-ODN p38 mitogen activated protein kinase
  • 相关文献

参考文献7

二级参考文献49

  • 1István Fri,Ferenc Sipos,Tiana M Germann,Alexandra Kalmár,Zsolt Tulassay,Béla Molnár,Gyrgyi Mzes.Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: Clinico-pathogenic aspects[J].World Journal of Gastroenterology,2013,19(26):4119-4126. 被引量:14
  • 2李丽英,王海燕,石建华,田莉.二磷酸果糖对老年大鼠缺血性急性肾功能衰竭的防护作用[J].中华医学杂志,1994,74(1):9-12. 被引量:7
  • 3胡海霞,苏东辉(审校).TLR家族在中枢神经系统中的免疫调节作用[J].国际免疫学杂志,2007,30(3):199-202. 被引量:2
  • 4Wang Y P, Sato C, Mizoguchi K, et al. Lipopolysaccharide trig- gers late preconditioning against myocardial infarction via inducible nitric oxide synthase[ J]. Cardiovasc Res, 2002, 56( 1 ): 33- 42.
  • 5Hiasa G, Hamada M, Ikeda S, et al. Ischemic preconditioning and lipopolysaccharlde attenuate nuclear factor-kappaB activation and gene expression of inflammatory cytokines in the ischemia- reperfused rat heart[J]. Jpn Circ J, 2001,65(11) : 984 -90.
  • 6Autieri MV. Inducible expression of the signal transduction protein 14-3-3gamma in injured arteries and stimulated human vascular smooth muscle cells [ J ] Exp Mol Pathol, 2004, 76 ( 2 ) : 99 - 107.
  • 7Cuenda A, Rousseau S. p38 MAP-kinases pathway regulation, function and role in human diseases [ J ]. Biochim Biophys Aeta, 2007, 1773(8) : 1358 -75.
  • 8Spector DL, Goldman RD, Leinwand LA. Culture and biochemical analysis ofceUs[ M]. Barker P. Ceils: A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press, 1998:11.1 -6.
  • 9Lavu M, Gundewar S, Lefer D J. Gene therapy for ischemic heart disease[J]. J Mol Cell Cardiol, 2011, 50(5): 742 -50.
  • 10Morrison D K. The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development[ J]. Trends Cell Biol, 2009, 19(1) :16 -23.

共引文献41

同被引文献8

引证文献3

二级引证文献20

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部