PDTC对大鼠慢性阻塞性肺疾病血流动力学的影响

目的探讨NF-κB抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）对慢性阻塞性肺病（COPD）各阶段的肺血流动力学及右心室壁厚度影响。方法将48只雄性SD大鼠随机分为八个组,分别纳入实验组及药物干预组,每组6只。实验组包括：A、B、C、D。正常对照组（A）：正常饲养4周;慢支组（B）：于实验第1、14天经气道内注入脂多糖（LPS）,200μg/次,4周后检测;COPD组（C）：第1、14天经气道内注入LPS,200μg/次,熏香烟1h/天,共4周;COPD并肺动脉高压组（D）：第1、14天经气道内注入LPS,200μg/次,熏香烟1h/天,共6周,实验的最后两周在熏香烟的同时,给予18%低氧8h/天。PDTC药物干预组为：A1（空白对照组）、B1（慢支干预组）、C1（COPD干预组）、D1（COPD并肺动脉高压干预组）。动物模型制作同各对应组,从第3周起给各药物干预组腹腔注射PDTC,剂量100mg·kg-1.d-1。A1组从第三周起腹腔注射同PDTC剂量相同的生理盐水。各组测定气道阻力、肺血流动力学和右心室肥厚指数,对肺组织行HE染色,观测气道的病理学改变,用免疫组化检测各组肺组织中NF-κB蛋白的表达。结果 C、D组RVSP、mPAP和RV/LV＋S都明显高于A组（P〈0.05）。C1、D1组RVSP、mPAP较C组、D组明显降低（P〈0.05）。D1组的RV/LV＋S值较D组有所降低（P〈0.05）。C、D组NF-κB蛋白表达强于A、B组（P〈0.05）,C1、D1组较实验组C、D组NF-κB蛋白含量下降。结论 COPD早期已出现肺血流动力学和右心室壁厚度的变化,PDTC干预后可抑制NF-κB蛋白表达,降低早期升高的平均肺动脉压力（mPAP）和右心室收缩压（RVSP）,减轻肺血管的重构,阻止右心室壁厚度的变化。

Effect of PDTC in pulmonary hemodynamics of rats with Chronic obstructive pulmonary diseas

Objective To investigate the effect of NF-κB inhibitor pyrrolidine dithiocarbamate（PDTC）on pulmonary hemodynamics and right ventricular wall at various stages of chronic obstructive pulmonary disease（COPD）.Methods 48 SD rats were divided into 8 groups randomly,integrating the experimental group and the medicine intervention group separately,each group of 6.The experimental group：A,B,C,D.Healthy control group（Group A）：rats were bred for 4 weeks in normal circumstance.Having a test 4 weeks later;Chronic bronchitis group（Group B）：200 μg lipopolysaccharide（LPS）was instilled intratracheally once at first and forteenth day for all rats.,a total of 4 weeks;COPD group（Group C）：200 μg LPS was instilled intratracheally once at first and forteenth day for all rats.Then these rats were exposed to cigarette smoke 1 h/d for 4 weeks;Pulmonary hypertension from COPD group（Group D）：200μg LPS was instilled intratracheally once at first and forteenth day and the rats were exposed to cigarette smoke 1h/d for 4 weeks.In last 2 weeks chronic hypoxia（FiO2=0.18）8h/d were performed simultaneously.The PDTC medicine intervention group：A1（Blank control group）,B1（Chronic bronchitis intervention group）,C1（COPD intervention group）,D1（Pulmonary hypertension from COPD intervention group）.The animal model manufacture following each corresponding group,Each group had the intraperitoneal injection of PDTC from fifteen day,doses of 100 mg·kg^-1·d^-1.A1 group was used the same dose of normal saline replace PDTC.We studied pulmonary hemodynamic changes,and the structure of right ventricular wall.HE strains were done,observing the pathological changes of the airway wall.The positive expression of NF-κB in lung tissue were detected by immunohistochemistry.Results The right ventricular systolic pressure（RVSP）,mean pulmonary arterial pressure（mPAP）and the ratio of the weight of right ventricle/left ventricle and septum（RV/LV＋S）were higher in group C,D than group A（P〈0.05）.Compared to the group C,D,the RVSP,mPAP in group C1,D1were significantly decreased（P〈0.05）.RV/LV＋S in group D is higher than in group D1（P〈0.05）.The expression of NF-κB protein in C,D group was significantly higher in the A,B group（P〈0.05）,Compared to experimental groups C,D;the NF-κB protein in group C1,D1 were decreased（P〈0.05）.Conclusions The changes of pulmonary hemodynamics and right ventricular wall had emerged at early COPD,the early intervention of PDTC can inhibit the expression of NF-κB protein,decrease the elevated pulmonary artery pressure and right ventricular systolic pressure,reduce the pulmonary vascular remodeling,preventing the changes of right ventricular wall thickness.