抑制黏着斑激酶-蛋白激酶B通路磷酸化对中心静脉导管留置诱导的兔颈外静脉损伤的保护作用  

Protective effect and mechanism of inhibition of focal adhesion kinase- protein kinase B signaling pathway phosphorylation to attenuate central venous catheter indwelling-induced external jugular vein injury in rabbits

作　　者：王彦茹[1,2] 赵艳杰[1] 林素兰[1] 郑玉建[2] WANG Yan-ru;ZHAO Yan-jie;LIN Su-lan;ZHENG Yu-jian(Nursing School,Xinjiang Medwal University,Ummqi,830054,Xinjiang Uyghur Autonomous Region,China;Public Health School,Xinjiang Medwal University,Ummqi,830054,Xinjiang Uyghur Autonomous Region,China)

机构地区：[1]新疆医科大学护理学院,新疆维吾尔自治区乌鲁木齐830011 [2]新疆医科大学公共卫生学院,新疆维吾尔自治区乌鲁木齐830011

出　　处：《中国临床药理学杂志》2021年第11期1358-1362,共5页The Chinese Journal of Clinical Pharmacology

基　　金：新疆维吾尔自治区自然科学基金资助项目(2020D01C150);新疆教育厅研究生科研创新基金资助项目(XJGRI2016083);新疆乌鲁木齐市科学技术计划基金资助项目(H161318002);新疆医科大学研究生创新创业基金资助项目(CXCY050)。

摘　　要：目的探讨抑制黏着斑激酶(FAK)-蛋白激酶B(Akt)通路磷酸化对中心静脉导管(CVC)留置诱导的兔颈外静脉损伤的保护作用及其机制。方法按照体重将新西兰兔随机分为3组:正常组、模型组和实验组,每组5只。经兔右颈外静脉插入CVC至右心房与上腔静脉交汇处,建立颈外静脉损伤模型。实验组用50μmol·L^(-1)的黏着斑激酶小分子抑制剂(Y15)溶液浸润CVC插管。插管后2,4和6周,苏木精-伊红染色观察颈外静脉病理改变,酶联免疫吸附法检测兔血清中活性氧簇(ROS)水平,蛋白质印迹法测定兔颈外静脉中磷酸化黏着斑激酶(p-FAK) Tyr 397的相对表达水平。结果干预4周后,模型组静脉腔内肉芽组织形成,大量炎细胞浸润;实验组血管内膜脱落。正常组、模型组和实验组的ROS水平分别为(32.65±1.97),(346.46±5.67)和(163.42±5.37)U·mL^(-1);这3组的p-FAK Tyr 397相对表达水平分别为0.13±0.02,3.41±0.04和0.49±0.03。模型组的上述指标与正常组比较、或实验组的上述指标与模型组相比,差异均有统计学意义(均P<0.001)。结论 Y15可减轻CVC留置诱导的颈外静脉损伤。Objective To explore the protective effect and mechanism on central venous catheter(CVC)indwelling-induced external jugular vein injury by inhibiting the phosphorylation of focal adhesion kinase(FAK)-protein kinase B(Akt)signaling pathway. Methods New Zealand rabbits were randomly divided into three groups according to weight: normal group, model group and experimental group, and 5 rabbits in each group. A CVC was inserted through the rabbit’s right jugular vein to the junction of the right atrium and superior vena cava to establish a model of external jugular vein injury.In the experimental group, CVCs before inserted were infiltrated with a 50 μmol·L^(-1) focal adhesion kinase small molecule inhibitor(Y15) solution. At the time of 2, 4, 6 weeks after inserted, the pathological changes of external jugular veins were observed by hematoxylin eosin staining, and the serum levels of reactive oxygen species( ROS) was detected by enzyme linked immunosorbent assay. The relative expression levels of phosphorylated focal adhesion kinase( p-FAK) Tyr 397 and p-Akt Ser 473 in the external jugular vein of rabbits were determined by Western blot. Results After 4 weeks of CVC placement,granulation tissue was organized in the venous cavity of the model group,and a large number of inflammatory cells were infiltrated;the vascular intima fell off in the experimental group. After 4 weeks of intervention,the ROS levels in the normal group,model group and experimental group were respectively( 32. 65 ± 1. 97),( 346. 46 ± 5. 67) and( 163. 42 ± 5. 37) U·m L^(-1);the relative expression levels of p-FAK Tyr 397 in the three groups were 0. 13 ± 0. 02,3. 41 ± 0. 04 and 0. 49 ± 0. 03. Compared between model group and normal group,or between the experimental group and model group at the same time point,the differences of all indicators in the model group were statistically significant( all P < 0. 001). Conclusion Y15 alleviated CVC indwelling-induced external jugular vein injury.

关 键 词：黏着斑激酶-蛋白激酶B信号通路 黏着斑激酶小分子抑制剂 中心静脉导管 静脉损伤 活性氧簇 

分 类 号：R97[医药卫生—药品]