摘要
目的探究重组骨桥蛋白(r-OPN)的抗炎机制对缓解蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)的作用。方法将48只大鼠随机分为假手术+安慰剂组(n=12)、SAH+安慰剂组(n=12)、SAH+r-OPN 0.03(0.03μg)组(n=12)和SAH+r-OPN 0.1(0.1μg)组(n=12)。采用枕大池二次注血法建立SAH模型。首次注血后72 h取脑脊液,处死大鼠,苏木精-伊红(HE)染色后测量基底动脉横截面积和管壁厚度,判断脑血管痉挛情况,Western blot测定基底动脉磷酸化c-Jun氨基末端激酶(p-JNK)水平,采用酶联免疫吸附法(ELISA)检测脑脊液中肿瘤坏死因子-α(TNF-α)及白介素-1β(IL-1β)水平。结果与SAH+安慰剂组相比,SAH+r-OPN 0.1组大鼠基底动脉横截面积明显增加,管壁厚度明显减轻,基底动脉p-JNK表达明显降低,脑脊液TNF-α、IL-1β水平明显降低。结论r-OPN能有效缓解SAH后CVS,其机制可能与降低p-JNK的表达,从而抑制TNF-α及IL-1β的产生,抑制SAH后的炎症反应有关。
Objective The anti-inflammatory mechanism of recombinant osteopontin (r-OPN) alleviating cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is investigated. Methods Forty-eight rats were randomly assigned to sham + vehicle group (n = 12 ), SAH + vehicle group (n = 12 ), SAH + r-OPN0. 03 ( 0. 03 μg) group (n = 12 ), and SAH + r-OPNO. 1 (0. 1μg) group (n = 12). The double injection model of cistema magna was induced. Cerebrospinal fluid (CSF) was collected and rats were sacrificed at 72 h after the first hemorrhage induction. The degree of CVS was determined by the measurement of the cress-sectional area and thickness of basilar arteries under hematoxylin-eosin (HE) staining. Western blot analysis was applied to evaluate the expression of phosphorylated c-Jun N-terminal kinase (p-JNK) in BA. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in CSF were tested using an enzyme-linked immunosorbent assays (ELISA) kit. Results The SAH + r-OPN0. 1 group showed significant increased cross-sectional area, decreased wall thickness, decreased expression of p-JNK in basilar arteries, declined TNF-α level and IL-1β level in CSF compared with the SAH + vehicle group. Conclusion r-OPN is demonstrated to alleviate CVS effectively, and its probable mechanism may be associated with the suppression of p-JNK expression, and subsequently inhibition of TNF-α and IL-1β production and suppression of inflammation after SAH.
出处
《中华神经外科疾病研究杂志》
CAS
2016年第1期25-28,共4页
Chinese Journal of Neurosurgical Disease Research
基金
南京市医学科技发展基金资助项目(YKK11115)
关键词
重组骨桥蛋白
蛛网膜下腔出血
脑血管痉挛
炎症
Recombinant esteopontin
Subarachnoid hemorrhage
Cerebral vasospasm
Inflammation