吗替麦考酚酯对肺动脉高压大鼠血管结构及细胞因子和受体的影响  

Effect of mycophenolate mofetil on vascular structure and cytokines and receptors of rat with pulmonary arterial hypertension

作　　者：张永锋[1] 郑毅[1] 

机构地区：[1]首都医科大学腑属北京朝阳医院风湿免疫科,100020

出　　处：《中华风湿病学杂志》2011年第9期625-628,I0005,共5页Chinese Journal of Rheumatology

基　　金：基金项目：国家自然科学基金（30872329）

摘　　要：目的观察吗替麦考酚酯对野百合碱诱导的肺动脉高压（PAH）大鼠肺动脉压力、碱性成纤维细胞生长因子（bFGF）、内皮素-1及受体的影响。方法建立野百合碱诱导的PAH大鼠模型。分为4组：正常对照组；野百合碱组；低剂量治疗组；高剂量治疗组，每组各8只。通过Masson染色显示肺泡内动脉血管壁肌化情况；测定收缩期肺动脉压力（SPAP）、右心室肥厚指数（RVI）、血清及肺匀浆中bFGF和受体、肺匀浆中内皮素-1及受体水平，各组间差异采用方差分析及q检验，方差不齐采用秩和检验。结果①高、低剂量治疗组与野百合碱组相比，SPAP[（40±13），（53＋10）与（68±10）mmHg]及RVI（0．36±0．06，0．38±0．03与0．44±0．05）均降低（P〈0．05）；②高、低剂量治疗组与野百合碱组相比，血清bFGF均降低[（2．3±1．9），（2．7±1．3）与（6．9±5．4）pg／ml，P〈0．05]；③高、低剂量治疗组与野百合碱组相比，肺泡内动脉血管壁肌化程度改善及肺小血管中肌性动脉数量减少。结论吗替麦考酚酯抑制血管肌化、降低SPAP和RVI，其机制可能通过抑制bFGF、内皮素-1及受体的表达抑制平滑肌增殖，从而达到缓解PAH。Objective To observe the effect of mycophenolate mofetil （MMF） on systolic pulmonary arterial pressure （SPAP）, right ventricle index （RVI）, cytokiues, receptors of pulmonary artery hypertension （PAH） rat models. Methods The rat models of monocrotaline （MCT）-PAH were developed. Thirty-two Sprague-Dawley male rats were divided randomly into four groups： the control group, the MCT, the MCT ＋ low-dose MMF （20 mg·kg^-1·d^-1, MMF 20） and the MCT ＋ high-dose MMF （40 mg·kg^-1·d^-1, MMF 40）. There were eight rats in each group. SPAP, RVI, cytokines and receptor in the serum and lung tissue were measured in all rats. Comparisons between multiple groups were performed with q test and rank sum test. Results （1） Low-dose and high-dose MMF group were compared with the MCT group, SPAP [（40±13）, （53±10） vs （68±10） mm Hg] and RVI （0.36±0.06, 0.38＋0.03 vs 0.44±0.05） were reduced and showed statistically significant difference respectively （P〈0.05）. （2） Compared with the MCT group, basic fibroblast growth factor （bFGF） of serum in both low-dose and high-dose MMF group were reduced and showed statistical difference respectively [ （2.3±1.9）, （2.7±1.3） vs （6.9±5.4） pg/ml, P〈0.05 ]. （3） Low-dose and high-dose MMF group were compared with the MCT group and showed that MA was decreased and the musculization of arterial wall was improved. Conclusion MMF can reduce SASP, RVI, number of MA. The inhibitory effect of MMF in PAH is possibly by inhibiting cytokines and receptors.

关 键 词：高血压 肺性 细胞因子类 成纤维细胞生长因子2 吗替麦考酚酯 

分 类 号：R543.2[医药卫生—心血管疾病]