CAJ | 학술논문

目的　研究血管活性肽在血管再狭窄形成中的作用。方法　在大鼠主动脉内皮球囊拉伤模型上，采用放射免疫法测定大鼠血浆及主动脉组织内皮素（ET）、降钙素基因相关肽（CGRP）和肾上腺髓质素（Adm）含量以及组织中血管紧张素Ⅱ（AⅡ）含量，用3H-TdR掺入法和组织学分析观察血管平滑肌细胞（VSMC）增生以及血管内膜/中膜面积比值。并在培养的VSMC上，采用3H-TdR掺入法研究血管活性肽对细胞增生的影响。采用RT-PCR法观察血管活性肽对自发性高血压大鼠（SHR）和WKY大鼠的主动脉和VSMC高血压相关基因-1（HRG-1）表达的影响。结果　术后10 d，血浆及主动脉ET达高峰，分别较对照组升高69%和124%（P<0.01）；主动脉AⅡ含量升高80%（P<0.01）。应用ET抗血清或卡托普利可明显抑制血管损伤诱导的VSMC增殖和内膜增厚。血浆和主动脉CGRP水平在术后3 d升高64%和89%（P<0.01），术后10 d血浆和组织Adm分别升高129%和102%（P<0.01）。在体应用CGRP(25 μg/kg)可显著抑制血管损伤诱导的VSMC增殖和内膜增厚（抑制率分别为66%和79%，P<0.01）。ET和AⅡ抑制血管HRG-1表达，激活丝裂素活化蛋白激酶（MAPK）；CGRP和Adm诱导HRG-1表达，并抑制MAPK活性。结论　ET和AⅡ可促进损伤血管内膜增殖，而CGRP和Adm具有代偿性抗内膜增殖作用。ET、AⅡ、CGRP和Adm等血管活性肽可通过调节HRG-1表达和MAPK途径以调控VSMC增殖，影响损伤血管狭窄的形成。
목적　연구혈관활성태재혈관재협착형성중적작용。방법　재대서주동맥내피구낭랍상모형상，채용방사면역법측정대서혈장급주동맥조직내피소（ET）、강개소기인상관태（CGRP）화신상선수질소（Adm）함량이급조직중혈관긴장소Ⅱ（AⅡ）함량，용3H-TdR참입법화조직학분석관찰혈관평활기세포（VSMC）증생이급혈관내막/중막면적비치。병재배양적VSMC상，채용3H-TdR참입법연구혈관활성태대세포증생적영향。채용RT-PCR법관찰혈관활성태대자발성고혈압대서（SHR）화WKY대서적주동맥화VSMC고혈압상관기인-1（HRG-1）표체적영향。결과　술후10 d，혈장급주동맥ET체고봉，분별교대조조승고69%화124%（P<0.01）；주동맥AⅡ함량승고80%（P<0.01）。응용ET항혈청혹잡탁보리가명현억제혈관손상유도적VSMC증식화내막증후。혈장화주동맥CGRP수평재술후3 d승고64%화89%（P<0.01），술후10 d혈장화조직Adm분별승고129%화102%（P<0.01）。재체응용CGRP(25 μg/kg)가현저억제혈관손상유도적VSMC증식화내막증후（억제솔분별위66%화79%，P<0.01）。ET화AⅡ억제혈관HRG-1표체，격활사렬소활화단백격매（MAPK）；CGRP화Adm유도HRG-1표체，병억제MAPK활성。결론　ET화AⅡ가촉진손상혈관내막증식，이CGRP화Adm구유대상성항내막증식작용。ET、AⅡ、CGRP화Adm등혈관활성태가통과조절HRG-1표체화MAPK도경이조공VSMC증식，영향손상혈관협착적형성。
Objective　To investigate the effects of several vasoactive peptides on the development of restenosis. Methods　The model of balloon angioplasty to the rat aorta was prepared and used to study the changes of endothelin (ET),angiotensin Ⅱ(AⅡ), calcitonin gene-related peptide (CGRP) and adrenomedullin(Adm) in the plasma and aorta tissues, with radioimmuno-assay.3?H-TdR incorporation and intima/media ratio of aortic tissue were measured after angioplasty. In cultured vascular smooth muscle cells, effects of these peptides on the proliferation of VSMC were evaluated with 3?H-TdR incorporation. Effects of these peptides on the expression of hypertension-related gene (HRG-1) in aorta tissue and cultured VSMC from SHR and WKY rats were studied by semi-quantitative RT-PCR. Results　After angioplasty, the levels of ET and AⅡ in the plasma and/or aorta tissue were significantly increased, with VSMC proliferation. On day 10 after angioplasty, the levels of ET in the plasma and tissue were increased by 69% and 124% respectively, compared with the that in the control group (P<0.01); and the levels of aortic AⅡ were increased by 80% (P<0.01). Antiserum against ET and angiotensin converting enzyme (ACE) inhibitors could obviously inhibit the proliferation of VSMC and neointima formation. Compared with the sham group on day 3 after angioplasty, the CGRP levels in plasma and aorta tissue were increased by 64% and 89% respectively (P<0.01); the Adm levels in the plasma and aorta tissue were increased by 129% and 102% respectively (P<0.01). On day 10, intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima formation induced by balloon aortic injury with the inhibitory rate of 66% and 79%, respectively, (P<0.01）. ET and AⅡ attenuated the expression of HRG-1 in the aorta, thus activating mitogen activated protein kinase (MAPK). CGRP and Adm potentiated the expression of HRG-1, thus inhibiting the activity of MAPK. Conclusions　ET and AⅡ stimulate the proliferation of injured intima, and CGRP and Adm have an anti-hyperplasia effects after angioplasty. That these peptides are suggested to be involved in the regulation of proliferation of VSMC and to affect the developing of vascular restenosis, by means of regulating the expression of HRG-1 and MAPK activities.