摘要
目的观察CX3CL1／fractalkine（FKN）在野百合碱诱导的肺动脉高压大鼠模型中的变化并探讨其在肺动脉高压发生、发展中的作用。方法将30只SPF级雄性Sprague-Dawley（SD）大鼠随机分为溶剂对照组（C组）、野百合碱2周组（M2组）和野百合碱3周组（M3组）。测量并比较各组肺动脉平均压（mPAP）、右心室平均压（mRVP）、颈动脉平均压（mCAP）、右心室游离壁（RV）和左心室加室间隔（LV＋S）重量比。光镜、电镜下分别观察肺细小动脉显微、超微结构变化，测定肺细小动脉管壁面积／管总面积（WA／TA）、肺细小动脉中膜厚度（PAMT）反映肺血管重塑情况，酶联免疫吸附试验测定血浆可溶性FKN（sFKN）浓度，免疫组织化学法测定肺小动脉FKN含量，逆转录聚合酶链反应测定肺组织中FKN mRNA的表达。结果①M2组[（20．58±3．54）mmHg、（18．14±2．47）mm Hg、（29．83±4．07）％]、M3组[（26．04±5．03）mm Hg、（22．17±5．63）mmHg、（59．52±12．86）％]mPAP、mRVP、RV／（LV＋S）均显著高于C组[（12．93±1．93）mm Hg、（11．66±1．81）mm Hg、（23．33±2．90）％]（P值均〈0．01），反映体循环的mCAP在各组之间差异无统计学意义。M2组[0．74±0．09、（27．36±2．02）μm]、M3组[0．87±0．04、（36．48±3．81）μm]WA／TA和PAMT均较C组[0．45±0．07、（13．91±1．51）μm]显著增高（P值均〈0．01）。②M2组血浆sFKN浓度和肺组织FKN mRNA相对含量[（677．76±101．75）ng／L、0．49±0．09J高于C组[（412．09±57．38）ng／L、0．11±0．06]，M3组血浆sFKN浓度和肺组织FKN mRNA相对含量[（1078．02±254．05）ng／L、0．64±0．04]高于M2组及C组（P值均〈0.01）。③M2组、M3组动脉管壁FKN蛋白（0．192±0．006、0．198±0．019）较C组（0．171±0．010）升高（P值均〈0．01），M2组与M3组之间差异无统计学意义。sFKN与PAMT、RV／（LV＋S）呈正相关（r值分别为0．796、0．710，P〈0．01），FKNmRNA与PAMT、RV／（LV＋S）呈正相关（r值分别为0．934，0．757，P〈0．01）。结论FKN及其介导的炎症反应在野百合碱诱导的肺动脉高压形成和发展及肺动脉重塑过程中可能起重要作用。
Objective To observe the change of CX3CL1/fractalkine （FKN） in the pulmonary hypertension rats induced by monocrotaline. Methods Thirty male Sprague-Dawley rats （270-310 g） were randomly divided into three groups： control group （C group）, monocrotaline two-weeks group （M2 group）, monocrotaline three-weeks group （M3 group）. The rats were weighed and anesthetized, then a catheter was placed through the right external iugular vein to the pulmonary artery to test the mean pulmonary arterial pressure （mPAF） and the mean right ventricle pressure （mRVP）. The mean carotid arterial pressure （mCAP） and the weight ratio of right ventricle （RV） to left ventricle plus septum （LV＋S） were also measured. The pathological model was assessed with mPAP, reCAP and RV/（LV＋S）. The structure change of pulmonary arterioles was observed under optical microscope. Remodeling of lung blood vessel was detected by measurement and calculation of the ratio of vessel wall area to total area （WA/TA） and the thickness of pulmonary artery media （PAMT）. The concentration of sFKN in plasma was measured by ELISA. Expression of FKN in the pulmonary artery wall was measured by the technique of immunohistochemistry. The level of FKN mRNA in lung 1issue was detected by RT-PCR. Results （i） The mPAP, mRVP and RV/（LV＋S） in model groups （M2, M3） were significantly higher than those in C group. The data of WA/TA and PAMT in model groups （M2,M3） were higher than those in C group. （2） sFKN and FKN mRNA in M2 [ （ 677.76 ± 101.75 ） ng/L, 0.49 ± 0.09 ] were higher than those in C group [-（412.09±57.38） ng/L,0. 11±0.06] （ P 〈0.01）, M3 group E（1 078.02±254.05） ng/L, 0.64±0.04]was higher than M2 group and C group （ P 〈0.01）. （3）FKN protein expression in the vessel wall of pulmonary arterioles in each group rats： FKN in model groups （ M2 group 0. 192 0. 006, M3 group：0.198±0.019） were more than that in group C （0.171±0.010, P 〈0.01）. There were no difference between group M3 and M2. The sFKN had a positive correlation with PAMT and RV/（LV＋S） （ r =0. 796,0. 710 respectively, P 〈0.01）, FKN mRNA had a positive correlation with PAMT and RV/（LV4-S） （ r =0. 934,0. 757 respectively, P 〈0.01L Conclusions FKN and inflammatory reaction play a key role in the formation and development of pulmonary hypertension induced by monocrotaline, and they probably participate in the progress of the pulmonary artery remodeling.
出处
《国际呼吸杂志》
2012年第2期106-112,共7页
International Journal of Respiration
