重组人血管内皮抑制素对COPD大鼠肺血流动力学指标的影响

Effect of recombinant human endostatin on the pulmonary hemodynamics in rats with COPD

目的观察重组人血管内皮抑制素对慢性阻塞性肺疾病(COPD)病程的影响及机制。方法将64只大鼠随机分为8组各8只,其中A组和B组分别于第1、14天气道内注入生理盐水及脂多糖(LPS)溶液;C组同上注入LPS溶液,同时采用香烟暴露法制备COPD模型,共1个月;D组同上注入LPS溶液并行香烟烟雾暴露及18%氧气吸入制备COPD并肺动脉高压(PAH)模型;B1组、C1组、D1组分别按B、C、D组造模,并腹腔注射重组人血管内皮抑制素;A1组处理方式同A组,并腹腔注射生理盐水。采用肺动脉插管法测定各组肺血流动力学指标,采用ELISA法检测肺泡灌洗液(BALF)中血管内皮生长因子(VEGF)蛋白表达情况,采用RT-PCR法、Western-blot法检测肺组织匀浆中VEGF mRNA及蛋白表达,分析VEGF表达与肺血流动力学指标的相关性。结果 C组和D组右心室收缩压(RVSP)、平均肺动脉压(mPAP)、右心室肥厚指数(RVHI)均明显高于A组,C1、D1组此三项指标均较对应C、D组下降(P均<0.05);C组和D组BALF中VEGF蛋白表达水平显著高于A组,C1、D1组VEGF蛋白表达较对应C、D组显著下降(P均<0.05);B组、C组和D组肺组织中VEGF mRNA及蛋白表达逐渐增强,B1、C1、D1组VEGF mRNA表达显著低于B组、C组和D组,C1、D1组VEGF蛋白表达显著低于C组和D组(P均<0.05);肺组织中VEGF mRNA及BALF中VEGF蛋白水平均与RVSP、mPAP呈正相关(P均<0.05)。结论重组人血管内皮抑制素可延缓COPD病情进展,可能机制为下调VEGF表达;此为COPD药物治疗提供了新的思路。

the effect and mechanism of recombinant human endostatin on the process of chronic obstructive pulmonary disease （COPD） . Methods Sixty-four SD rats were divided into 8 groups randomly with 8 in each group. Saline and LPS were separately injected into trachea at 1st and 14th day for the rats of group A and B. LPS was injected into trachea at the same way of the rats in group C , and then were exposed to cigarette smoke for a month to make the model of COPD. Beside that, the rat′s trachea was injected with LPS and then were exposed to cigarette smoke at the same way in group D, the rats were in hypoxia （FiO2 =0.18） for a month simultaneously to make the model of COPD with PAH. The rats model in group B1, C1, D1 were made separately according to group B, C, D, and recombinant human endostatin were given by intraperitoneal injection in this three group. The Al group was treated according to group A, and were given saline by intraperitoneal injection. The pulmonary hemedynamics was determined by using pulmonary artery intubation, VEGF expression in BALF was detected by ELISA, VEGF mRNA and VEGF protein expression in lung tissue were separately detected by RT-PCR and Western-blot , the reIevance of VEGF expression and pulmonary hemodynamics were analyzed. Results The right ventricular systolic pressure （ RVSP）, mean pulmonary arterial pressure （ mPAP）, right ventricle hypertrophy inde（RVHI） in group C and D were obviously higher than those in group A , and this three targets in group C1 and D1 were separately lower than those in group C and D（ P 〈 0.05 ） ; The VEGF expression in BALF in group C and D were obviously higher than that in group A , and which in group C1 and D1 were separately lower than that in group C and D（P 〈 0.05 ） ; The VEGF mRNA and protein expression of rats in group B, C and D strengthened gradually. The VEGF mRNA expression in group B1, C1 and D1 were obviously lower than that in group B, C and D. The VEGF protein expression ingroup C1 and D1 were obviously lower than that in group C and D（P 〈0.05） ;The VEGF mRNA expression in lung tissue and the VEGF protein expression in BALF were separately related with RVSP, mPAP （ P 〈 0.05 ）. Conclusions Recombinant human endostatin has the ability to delay the COPD condition progress, and the possible mechanism is to decline the VEGF expression; this study provides new mentality for the pharmacological treatment of COPD.