Kindlin-2 RNA干扰减轻大鼠颈动脉内膜增生
作者:
作者单位:

(襄阳市中心医院 湖北文理学院附属医院心血管内科,湖北省襄阳市 441000)

作者简介:

周青,硕士,主治医师,研究方向为冠心病的机制研究,E-mail为jgzhq3000@163.com。通信作者吴校林,博士,副主任医师,研究方向为冠心病的机制研究,E-mail为wxling.23@163.com。

基金项目:

国家自然科学基金青年项目(81600288)


Kindlin-2 RNA interference alleviates intimal hyperplasia of rat carotid arteries
Author:
Affiliation:

Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, Hubei, China)

  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
    摘要:

    目的 观察Kindlin-2 RNA干扰对球囊损伤的大鼠颈动脉内膜增生的影响。方法 构建并制备Kindlin-2 siRNA和阴性对照慢病毒载体并感染球囊损伤的大鼠颈动脉, 1周和4周后取损伤的颈动脉,实时定量PCR检测Kindlin-2 mRNA的表达,HE染色评估术后4周颈动脉内膜增生情况,并行免疫荧光或免疫组化检测颈动脉中Kindlin-2、α-actin、PCNA和β1整合素的表达,Masson染色了解颈动脉中胶原纤维合成情况。结果 Kindlin-2 RNA干扰能明显降低1周时颈动脉中Kindlin-2 mRNA的表达水平(P<0.05),并显著抑制4周后颈动脉的内膜增生(P<0.05)。与阴性对照组相比,Kindlin-2 siRNA组术后4周颈动脉中Kindlin-2、α-actin、PCNA和β1整合素的表达水平均明显降低,颈动脉内膜和中膜胶原纤维的合成也减少。结论 Kindlin-2 RNA干扰可能通过抑制血管平滑肌细胞增殖、迁移和细胞外基质合成减轻血管内膜增生。

    Abstract:

    Aim To observe the effects of Kindlin-2 RNA interference on intimal hyperplasia in the balloon injured rat carotid arteries. Methods Kindlin-2 siRNA and negative control lentiviral vectors were constructed and produced, then balloon injured rat carotid arteries were infected with lentivirus. Carotid arteries were collected at 1 and 4 weeks after operation. The expression level of Kindlin-2 mRNA in the rat carotid arteries was detected by real-time quantitative PCR technique. The degree of intimal hyperplasia 4 weeks after balloon injury was assessed by HE staining. The immunofluorescence and histochemistry were used to detect the protein expression of Kindlin-2, α-actin, PCNA and β1-integrin in the carotid arteries. The synthesis of collagen fibers in the carotid arteries was investigated by Masson staining. Results Kindlin-2 RNA interference can significantly reduce the Kindlin-2 mRNA expression level in the rat carotid arteries at 1 week(P<0.05), and significantly inhibited intimal hyperplasia of carotid arteries 4 weeks after balloon injury (P<0.05). Compared with the negative control group, the protein expression levels of Kindlin-2, α-actin, PCNA and β1-integrin were significantly decreased in the carotid arteries of the Kindlin-2 group 4 weeks after operation. The synthesis of collagen fibers in the carotid arteries intima and media was also reduced. Conclusion Kindlin-2 RNA interference may inhibit vascular smooth muscle cell proliferation, migration and extracellular matrix synthesis to alleviate intimal hyperplasia.

    参考文献
    [1] Curcio A, Torella D, Indolfi C.Mechanisms of smooth muscle cell proliferation and endothelial regeneration after vascular injury and stenting:approach to therapy.Circ J, 1,5(6):1287-1296.
    [2] Chistiakov DA, Orekhov AN, Bobryshev YV.Vascular smooth muscle cell in atherosclerosis.Acta Physiol (Oxf), 5,4(1):33-50.
    [3] Sakakura K, Nakano M, Otsuka F, et al.Pathophysiology of atherosclerosis plaque progression.Heart Lung Circ, 3,2(6):399-411.
    [4] Subbotin VM.Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target.Drug Discov Today, 6,1(10):1578-1595.
    [5] 徐健, 冯丰, 刘闺兰, 等.转染OPN-002-siRNA对大鼠颈动脉球囊损伤后内膜增生和OPN、TGF-β1、PCNA表达的影响.中国动脉硬化杂志, 5,3 (11):1107-1112.
    [6] Lai-Cheong JE, Parsons M, McGrath JA.The role of kindlins in cell biology and relevance to human disease.Int J Biochem Cell Biol, 0,2(5):595-603.
    [7] Lee SY, Hong MK, Jang Y.Formation and transformation of neointima after drug-eluting stent implantation:insights from optical coherence tomographic studies.Korean Circ J, 7,7(6):823-832.
    [8] 许振业, 柳景华, 王韶屏, 等.经皮冠状动脉介入治疗对内皮功能影响的研究进展.心肺血管病杂志, 6,7(35):584-587.
    [9] Qiu Y, Lam JK, Leung SW, et al.Delivery of RNAi therapeutics to the airways-from bench to bedside.Molecules, 6,1(9):pii:E1249.
    [10] Bledzka K, Bialkowska K, Sossey-Alaoui K, et al.Kindlin-2 directly binds actin and regulates integrin outside-in signaling.J Cell Biol, 6,3(1):97-108.
    [11] Montanez E, Ussar S, Schifferer M, et al.Kindlin-2 controls bidirectional signaling of integrins.Genes Dev, 8,2(10):1325-1330.
    [12] Pluskota E, Dowling JJ, Gordon N, et al.The integrin coactivator kindlin-2 plays a critical role in angiogenesis in mice and zebrafish.Blood, 1,7(18):4978-4987.
    [13] Qu H, Tu Y, Shi X, et al.Kindlin-2 regulates podocyte adhesion and fibronectin matrix deposition through interactions with phosphoinositides and integrins.J Cell Sci, 1,4(Pt 6):879-891.
    [14] Cheah M, Andrews MR.Integrin activation:implications for axon regeneration.Cells, 8,7(3).pii:E20.
    [15] Malinin NL, Pluskota E, Byzova TV.Integrin signaling in vascular function.Curr Opin Hematol, 2,9(3):206-211.
    [16] Li P, Zhu N, Yi B, et al.MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and vascular neointimal formation.Circ Res, 3,3(10):1117-1127.
    [17] Petersen JW, Douglas JY.Tenascin-X, collagen, and Ehlers-Danlos syndrome:tenascin-X gene defects can protect against adverse cardiovascular events.Med Hypotheses, 3,1(3):443-447.
    相似文献
    引证文献
引用本文

周青,吴校林,卞芳,李宸宇,朱通建,胡河. Kindlin-2 RNA干扰减轻大鼠颈动脉内膜增生[J].中国动脉硬化杂志,2018,26(10):993~998.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:2018-05-14
  • 最后修改日期:2018-05-27
  • 在线发布日期: 2018-11-09