红景天和葛根素对高原地区慢性阻塞性肺疾病急性加重期合并慢性肺源性心脏病患者肺动脉高压的干预作用研究

摘要

Objective To investigate the intervention effectiveness of rhodioside and puerarin on pulmonary arterial hypertension(PAH)in patients with chronic obstructive pulmonary disease in acute exacerbation(AECOPD) stage complicated by chronic cor pulmonale(CCP)at high altitude areas. Methods A prospective randomized clinical contrast method was conducted. Designed with random digits table method,138 patients with AECOPD and CCP at high-altitude(2260-3500 m above sea level)were divided into three groups(each,n=46):control group, rhodioside treated group and puerarin treated group. All patients in the three groups received routine treatment of anti-infection,expectorant,antiasthma,oxygen,etc. therapies. Each patient in rhodioside treated group received 2.0 g of rhodioside orally,3 times daily,in puerarin treated group received 0.2 g of puerarin by intravenous drip,once daily, and in control group received routine treatment,the therapeutic course being 28 days in all the three groups. Levels of endothelin-1(ET-1),nitric oxide(NO),nitric oxide synthesis(NOS),mean pulmonary arterial pressure(mPAP), outflow tract of right ventricle(RVOT),internal diameter of right ventricle(RVID),partial pressure of arterial oxygen (PaO2)and partial pressure of arterial carbon dioxide(PaCO2)were measured before treatment and on the 14th day, and 28th day after treatment. Results Before treatment,levels of ET-1,NO,NOS,mPAP,RVOT,RVID, PaO2 and PaCO2 showed no significant differences among three groups(all P>0.05). Along with the prolongation of therapeutic time,compared with those before treatment,the plasma levels of ET-1,mPAP,RVOT,RVID,and PaCO2 on the 14th day and 28th day after treatment were significantly decreased in the three groups,however the levels of NO,NOS,and PaO2 were significantly increased. The above parameters reached their valley or peak values on the 28th day after treatment in the three groups. All parameters on the 14th day and 28th day in rhodioside treated group and puerarin treated group had significant differences compared with those in the control group(P<0.05 or P<0.01), 28th day after treatment,the improvement in rhodioside treated group being more obvious than that in puerarin treated group〔ET-1(μg/L):63.9±9.1 vs. 74.8±9.8,mPAP(mm Hg,1 mm Hg=0.133 kPa):32.4±4.6 vs. 38.2±4.8, RVOT(mm):31.3±3.2 vs. 33.6±3.3,RVID(mm):24.3±2.8 vs. 27.7±2.8,PaCO2(mm Hg):42.5±5.1 vs. 46.7±5.2,NO(μmol/L):70.3±9.1 vs. 58.2±8.3,NOS(μmol/L):25.6±2.8 vs. 20.5±2.7,PaO2(mm Hg):54.9±5.6 vs. 50.8±5.5〕,there were statistical significant differences(all P<0.01). Correlation analyses showed that the level of ET-1 was significantly positively correlated with mPAP(r=0.838,P<0.01),and was significantly negatively correlated with NO and PaO2(r1=-0.802,r2=-0.765,both P<0.01);the level of NO was significantly negatively correlated with mPAP(r=-0.835,P<0.01),and was significantly positively correlated with PaO2 (r=0.743,P<0.01)in 138 patients with AECOPD and CCP. Conclusions Rhodioside and puerarin are effective in treatment of PAH in patients with AECOPD complicated by CCP at high altitude,and the effect of rhodioside is more effective than puerarin. The mechanism of the therapy is probably related to the inhibition of ET-1 synthesis or release and promotion of NO synthesis or release from lung vascular endothelial cells that can regulate the imbalance between vascular dilative and constrictive substances,thus PAH is descendent.%　　目的探讨红景天和葛根素对高原地区慢性阻塞性肺疾病急性加重期(AECOPD)合并慢性肺源性心脏病(CCP)患者肺动脉高压(PAH)的干预效果.方法采用前瞻性随机对照研究方法.按随机数字表法将138例高原地区(海拔2260~3500 m)AECOPD合并CCP患者分为对照组、红景天治疗组和葛根素治疗组,每组46例.3组患者均给予抗感染、祛痰、平喘、吸氧等常规治疗,在此基础上,红景天治疗组口服红景天胶囊,每次2.0 g,每日3次,共28 d；葛根素治疗组静脉滴注葛根素,每次0.2 g,每日1次,共28 d.于治疗前和治疗14 d、28 d分别测定血中内皮素-1(ET-1)、一氧化氮(NO)、一氧化氮合酶(NOS)水平及平均肺动脉压(mPAP)、右心室流出道(RVOT)、右心室内径(RVID)、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2).结果3组治疗前ET-1、NO、NOS、mPAP、RVOT、RVID、PaO2、PaCO2比较差异均无统计学意义(均P>0.05)；随治疗时间延长,3组ET-1、mPAP、RVOT、RVID、PaCO2均显著降低,NO、NOS和PaO2显著升高,治疗28 d达谷值或峰值.红景天治疗组和葛根素治疗组治疗14 d、28 d各指标与对照组比较差异均有统计学意义(P<0.05或P<0.01),且治疗28 d时红景天治疗组各项指标改善程度均较葛根素治疗组为优〔ET-1(μg/L)：63.9±9.1比74.8±9.8,mPAP(mm Hg,1 mm Hg=0.133 kPa)：32.4±4.6比38.2±4.8,RVOT(mm)：31.3±3.2比33.6±3.3,RVID(mm)：24.3±2.8比27.7±2.8,PaCO2(mm Hg)：42.5±5.1比46.7±5.2,NO(μmol/L)：70.3±9.1比58.2±8.3,NOS(μmol/L)：25.6±2.8比20.5±2.7,PaO2(mm Hg)：54.9±5.6比50.8±5.5〕,差异均有统计学意义(均P<0.01).直线相关分析显示,ET-1与mPAP呈显著正相关(r=0.838,P<0.01),与NO、PaO2呈显著负相关(r1=-0.802,r2=-0.765,均P<0.01)；NO与mPAP呈显著负相关(r=-0.835,P<0.01),与PaO2呈显著正相关(r=0.743,P<0.01).结论红景天和葛根素治疗高原地区AECOPD合并CCP患者的PAH是有效的,且红景天疗效更好,其机制可能是它们对肺血管内皮细胞ET-1合成、释放的抑制,而对NO合成与释放的促进,调节了舒/缩血管物质的失衡,从而使PAH降低.