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Roscovitine通过影响核因子κB活化抑制大鼠颈动脉内膜损伤导致的炎性增生

发布时间:2018-01-31 00:40

  本文关键词: Roscovitine 核因子κB 颈动脉内膜 炎性增生 出处:《中国病理生理杂志》2017年02期  论文类型:期刊论文


【摘要】:目的:探讨roscovitine通过影响核因子κB(nuclear factor-κB,NF-κB)活化抑制大鼠颈动脉内膜损伤导致炎性增生的作用及其分子机制。方法:随机将SD大鼠分成对照组、模型组和治疗组3组,每组20只。模型组采用胰蛋白酶消化法制作颈动脉内膜损伤模型;对照组采用假手术用生理盐水代替胰蛋白酶消化步骤,其他同模型组操作;治疗组在分离的颈动脉血管外壁均匀涂抹终浓度为2 g/L roscovitine缓释凝胶0.5 mL,其他同模型组。各组大鼠术后常规饲养4周后取材备检。采用HE染色观察各组形态学变化,采用Western blot法检测IκB的表达变化和磷酸化降解,检测NF-κB的表达变化、磷酸化激活以及其下游环氧合酶2(cyclooxygenase-2,COX-2)、血管细胞黏附分子1(vascular cell adhesion molecule-1,VCAM-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素6(interleukin-6,IL-6)的表达变化。结果:Roscovitine通过抑制胰蛋白酶损伤诱导的IκB-α磷酸化降解,阻断NF-κB-p65的磷酸化活化,进而下调COX-2表达,抑制VCAM-1、TNF-α和IL-6的表达,从而发挥抑制损伤血管内膜增生的作用。结论:Roscovitine通过影响NF-κB活化抑制大鼠颈动脉内膜损伤导致的炎性增生。
[Abstract]:Objective: to investigate the effect of roscovitine on nuclear factor- 魏 B (NF- 魏 B). Effects of NF- 魏 B activation on inflammatory hyperplasia induced by carotid intimal injury in rats and its molecular mechanism. Methods: SD rats were randomly divided into three groups: control group, model group and treatment group. There were 20 rats in each group. The model group was treated with trypsin digestion method to make carotid intima injury model. The control group was treated by sham operation with normal saline instead of trypsin digestion step, and the other model group was operated with normal saline instead of trypsin. In the treatment group, the final concentration of 2 g / L roscovitine sustained release gel was 0. 5 mL on the external wall of the isolated carotid artery. Other same model groups. The rats in each group were routinely fed for 4 weeks after operation. The morphological changes of each group were observed by HE staining. I 魏 B expression and phosphorylation degradation and NF- 魏 B expression were detected by Western blot assay. Phosphorylation and its downstream cyclooxygenase-2 cyclooxygenase-2 (COX-2). Vascular cell adhesion molecule-1 (VCAM-1). Tumor necrosis factor- 伪 (TNF- 伪) and interleukin-6 (IL-6). Results the phosphorylation of NF- 魏 B-p65 was blocked by inhibiting the phosphorylation of I 魏 B- 伪 induced by trypsin injury. The expression of COX-2 was down-regulated and the expression of TNF- 伪 and IL-6 in VCAM-1 was inhibited. Conclusion: Roscovitine inhibits inflammatory hyperplasia induced by carotid intima injury by affecting NF- 魏 B activation.
【作者单位】: 河北中医学院基础医学院生物化学与生物学教研室;河北省心脑血管病中医药防治重点实验室;河北省人民医院;
【基金】:国家自然科学基金资助项目(No.31271466;No.81573698) 河北省科技支撑计划(No.13277739D) 河北省教育厅科技类重点项目(No.ZD2014005) 河北省自然科学基金资助项目(No.2009001053)
【分类号】:R543.4
【正文快照】: 随着社会的老龄化,动脉粥样硬化性疾病的发病率逐年升高,已经成为严重危害人类健康的主要疾病。虽然动脉粥样硬化性疾病的发病机理尚未完全阐明,但经多年的发展,血管搭桥术、动脉球囊扩张术及支架置入术等多种形式的血管重建术已经成为治疗这类疾病常用而有效的方法[1];然而,

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