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]