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抑制核因子-κB信号通路在血栓闭塞性脉管炎中的治疗机制

Inhibition of the therapeutic mechanism of nuclear factor-κB signaling pathway in thromboangiitis obliterans

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【作者】 唐忠尉田野张磊胡阳李新喜

【Author】 Tang Zhongwei;Tian Ye;Zhang Lei;Hu Yang;Li Xinxi;Department of Vascular Surgery, the First Affiliated Hospital of Xinjiang Medical University;Department of Urology, the First Affiliated Hospital of Xinjiang Medical University;

【通讯作者】 李新喜;

【机构】 新疆医科大学第一附属医院血管甲状腺外科新疆医科大学第一附属医院泌尿外科

【摘要】 目的 探讨抑制核因子-κB(NF-κB)信号通路治疗血栓闭塞性脉管炎(TAO)的机制。方法 选取2020年4—7月于新疆医科大学实验动物中心饲养的40只SPF级Wistar雄性大鼠,将其随机分为对照组、假手术组、TAO模型组和NF-κB抑制组,每组10只,通过注射月桂酸钠建立TAO模型,给药21 d后对各组大鼠进行病变分级评分;取材后进行苏木精-伊红染色法(HE)染色,观察镜下病理组织变化。比较各组大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-8水平,大鼠股动脉组织中细胞间黏附分子(ICAM-1)、血管细胞黏附分子(VCAM-1)、E-选择素(E-selection,ES)mRNA表达水平及p65、p50蛋白表达水平。结果 与TAO模型组相比,NF-κB抑制组大鼠患肢病变减少,差异有统计学意义(P﹤0.05)。TAO模型组大鼠血清中TNF-ɑ、IL-6、IL-8水平均高于对照组、假手术组、NF-κB抑制组大鼠,差异均有统计学意义(P﹤0.05)。TAO模型组大鼠动脉组织中ICAM-1、VCAM-1水平均高于对照组和假手术组大鼠,差异均有统计学意义(P﹤0.05)。TAO模型组大鼠动脉组织中ICAM-1、ES水平均高于NF-κB抑制组大鼠,差异均有统计学意义(P﹤0.05)。TAO模型组大鼠p65、p50蛋白表达水平均高于对照组、假手术组、NF-κB抑制组大鼠,差异均有统计学意义(P﹤0.05)。结论 NF-κB信号通路的激活与TAO发生有关,可通过抑制NF-κB信号通路来抑制炎性反应,从而发挥对TAO的治疗作用。

【Abstract】 Objecive To investigate the mechanism of inhibition of nuclear factor-κB(NF-κB) signaling pathway in the treatment of thromboangiitis obliterans(TAO). Method A total of 40 male rats of SPF-grade Wistar were raised at the Laboratory Animal Center of Xinjiang Medical University from April to July 2020. They were randomly divided into control group, sham group, TAO model group and NF-κB suppression group, with 10 animals in each group. The TAO model was established by injection of sodium laurate, and the lesion grading scores were performed on each group of rats after 21 d. After taking the material, hematoxylin-eosin staining(HE) staining was performed, and the pathological tissue changes were observed under the microscope. The serum tumor necrosis factor-α(TNF-α), interleukin(IL)-6 and IL-8 levels, the expression levels of intercellular adhesion molecules(ICAM-1), vascular cell adhesion molecules(VCAM-1)and E-selection(ES) mRNA in rat femoral artery tissues, the expression levels of p65 and p50 proteins in the femoral artery tissues of all groups were compared. Result Compared to the TAO model group, the pathological changes in the affected limbs of rats in the NF-κB inhibition decreased significantly, the difference was statistically significant(P<0.05).The serum levels of TNF-α, IL-6 and IL-8 in TAO model group were higher than those in control group, sham operation group and NF-κB inhibition group, the differences were statistically significant(P<0.05). The levels of ICAM-1 and VCAM-1 in arterial tissues of TAO model group were higher than those of control group and sham operation group, the differences were statistically significant(P<0.05). The expression levels of ICAM-1 and ES in arterial tissue of TAO model rats were higher than those of NF-κB inhibition group, the differences were statistically significant(P<0.05). The levels of p65 and p50 proteins in TAO model group were higher than those in control group, sham operation group and NF-κB inhibition group, the differences were statistically significant(P<0.05). Conclusion Activation of the NF-κB signaling pathway is associated with TAO. The inflammatory response could be inhibited by the supression of the NF-κB signaling pathway, thereby exerting a therapeutic effect on TAO.

【基金】 新疆维吾尔自治区自然科学基金资助项目(2019D01C295)
  • 【文献出处】 血管与腔内血管外科杂志 ,Journal of Vascular and Endovascular Surgery , 编辑部邮箱 ,2023年02期
  • 【分类号】R543
  • 【下载频次】22
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