长期雾化吸入硝酸甘油对高肺血流大鼠肺动脉压力及肺血管结构重建的影响

目的探讨长期雾化吸入硝酸甘油对高肺血流大鼠肺动脉压力、肺血管结构的作用及其机制。方法24只健康雄性Wistar大鼠随机分为对照组、分流组和吸入组。对分流组和吸入组大鼠开腹行腹主动脉-下腔静脉分流术,12周后两组大鼠分别雾化吸入生理盐水和硝酸甘油3周。以右心导管法测定肺动脉压,颈动脉插管测定体循环压,检测右心室肥厚,观测肺血管显微及超微结构变化,用免疫组织化学法检测大鼠肺动脉人类尾加压素Ⅱ(hUⅡ)的表达。结果分流组大鼠肺动脉平均压(PAMP)和右心室/左心室 室间隔重量比值(RV/LV S)明显高于对照组(P<0.01),且分流组大鼠肺小血管肌化程度明显增强(P<0.01),中、小型肺肌型动脉相对厚度(RMT)增加,肺动脉内皮细胞和平滑肌细胞hUⅡ表达明显增强。吸入组大鼠mSBP未受影响,PAMP明显低于分流组(P<0.01),RV/(LV S)高于对照组(P<0.01),但与分流组比较差异无显著性(P>0.01),吸入组大鼠肺小血管肌化程度明显改善,小型肺肌型动脉RMT及小型肺动脉内皮细胞和平滑肌细胞hUⅡ减少。结论长期雾化吸入硝酸甘油可缓解高肺血流量所致肺动脉高压和肺血管结构的重建,其对肺动脉内皮细胞和平滑肌细胞hUⅡ表达的抑制作用,可能参与高肺血流量所致肺血管结构重建和肺动脉高压的调节。     

左向右分流致肺动脉高压对大鼠肺动脉胶原代谢的影响

目的建立左向右分流所致肺动脉高压大鼠模型,了解高肺血流量对肺血管胶原代谢的影响。方法对大鼠行腹主动脉下腔静脉分流术。术后11周以右心导管法测定肺动脉平均压(PAMP),采用免疫组织化学法检测大鼠肺动脉Ⅰ、Ⅲ型胶原蛋白的表达。结果分流11周后大鼠肺循环与体循环血流量之比分别为3.3∶1.0,为大量左向右分流。PAMP较对照组明显升高(P<0.01)。分流组大鼠肺中、小型肺动脉中Ⅰ、Ⅲ型胶原蛋白表达与对照组比较明显增加。结论高肺血流量可导致肺动脉高压,并促进肺动脉高压大鼠细胞外基质/胶原的堆积。     

L—精氨酸对高肺血流量所致肺动脉高压的防治作用

目的 探讨L－精氨酸对高肺血流量所致肺动脉高压的防治作用。方法 21只雄性SD大鼠随机分为对照组（n=6)、分流组（n=7)和分流＋L－精氨酸组（n=8)。对分流组和分流＋L－精氨酸组大鼠行腹主动脉－下腔静脉分流术。11周后以右心导管法测定肺动脉平均压（mPAP)。检测右心室／体重（RV／BW）和右心室／左心室＋室间隔（RV/LV S)比值。并且观测肺血管结构的变化。结果 分流组大鼠mPAP、RV／BW及RV/(LV S）比值明显高于对照组（P均＜0．01）,且分流组大鼠肺小血管肌化程度明显增强,肺中、小肌型动脉相对中膜面积及厚度明显增加。而分流＋L－精氨酸组大鼠mPAP、RV／BW及RV／LV＋S比值明显低于分流组（P均＜0．05）,L－精氨酸缓解了肺血管结构重建的形成。结论 L－精氨酸对高肺血流量所致肺血管结构重建及肺动脉高压有重要的调节作用。     

高肺血流量对肺血管结构及内源性硫化氢影响

目的 探讨高肺血流量所致肺动脉高压(PH)大鼠肺血管结构和血浆硫化氢的变化。方法 雄性SD大鼠共16只。对分流组大鼠行腹主动脉、下腔静脉分流术;11周后以右心导管法测定肺动脉平均压(mPAP);检测右心室/体重(RV/BW)和右心室/左心室+室间隔(RV/LV+S)比值;并以光学显微镜和电子显微镜观测肺血管结构变化;以分光光度法测定血浆硫化氢含量。结果 分流组大鼠mPAP、RV/BW及RV/(LV+S)比值均明显高于对照组(P均<0.01);光镜下肺小血管肌化程度明显增强,肺中、小肌型动脉相对中膜厚度明显增加;电镜下,肺中、小肌型动脉内皮细胞增生、肥厚、肿胀,平滑肌细胞增生、肥厚,并由收缩表型向合成表型转化。分流组大鼠的血浆H_2S含量明显低于对照组,肺动脉平均压与血浆硫化氢含量呈负相关。结论 肺血管结构重建是高肺血流量所致PH重要病理基础,内源性H_2S下调可能在其形成中起重要作用。     

雾化吸入硝酸甘油对先天性心脏病并肺动脉高压患儿血流动力学的影响

目的了解雾化吸入硝酸甘油(Nebulized nitroglycerin Neb-NTG)对先天性心脏病并肺动脉高压患儿血流动力学的影响,探讨治疗肺动脉高压的的新途径.方法采用空气压缩泵作为雾化发生器吸入NTG[20μg/(lg·次)],动态监测患儿血压、心率,于吸入Neb-NTG前、吸入后10 min、吸入后30～60 min及吸入Neb-NTG治疗3 d后超声心动图测量左室射血分数(EF)和短轴缩短率(FS)、右室射血前期(RPER)、加速时间(AT)、肺动脉平均压(PAMP)、肺动脉收缩压(PASP)和肺动脉峰值血流速度(PA)的变化.结果Neb-NTG对血压、心率、EF、FS和PA无影响(P＞0.05);吸入Neb-NTG后10 min、30～60 min RPER/AT、PAMP和PASP有下降趋势,但与吸入前比较,差别无显著性意义(P＞0.05);吸入Neb-NTG 3 d后RPEP/AT、PAMP和PASP明显下降,分别由0.97±0.33 mmHg降至0.81±0.31 mmHg、39±13 mmHg降至30±12 mmHg、54±17 mmHg至43±13 mmHg,与吸入前比较,差别有显著性意义(P＞0.05).结论吸入Neb-NTG可能是一种有效的、简单的、选择性的、优于静脉NTG的肺血管扩张剂,本研究为肺动脉高压治疗提供了新的途径和新的思路.     

高肺血流量及长期雾化吸入硝酸甘油对肺血管舒张反应的影响

目的　以左向右分流的大鼠为对象 ,观察高肺血流量及长期雾化吸入硝酸甘油 (NTG)对肺血管舒张反应的影响。方法　雄性Wistar大鼠 1 7只 ,分为吸入组 (n =5)、分流组 (n =5)和对照组 (n =7)。分流组和吸入组用手术造成腹主动脉和下腔静脉之间左向右分流。手术后饲养 1 2周 ,开始压力喷射雾化吸入。吸入组吸入NTG ,分流组和对照组吸入生理盐水 ,每日吸一次 ,每次吸 1 0min ,共吸 3周。之后取肺动脉环离体灌流 ,观察其对乙酰胆碱 (Ach)、硝普钠、NTG的舒张反应。结果　与对照组相比 ,吸入组和分流组的肺动脉环对Ach舒张反应明显减弱 (P <0 .0 5) ;三组血管环对硝普钠和NTG舒张反应无明显差别。结论　高肺血流量产生的高切应力损伤了肺动脉对Ach的舒张功能 ,长期雾化吸入NTG没有使之改善。     

肺动脉高压治疗的一种新途径--雾化吸入一氧化氮供体有效性的研究进展

一氧化氮(nitric oxide,N0)是血管内皮细胞释放的内皮依赖性的舒张因子(endothelium—derived relaxing factor EDRF)。NO具有极其广泛的生理作用,而它通过增加血管平滑肌细胞内eGMP的浓度扩张肺血管作用最为重要。这一研究的发现使得近十年来肺动脉高压(pulmonary hypertension,PH)的治疗领域取得了惊人的进步,即证实了     

雾化吸入一氧化氮供体治疗肺动脉高压研究进展

一氧化氮（NO）吸入作为一种选择性的肺血管扩张剂,临床上已应用于多种疾病的治疗,并取得了良好疗效,但由于NO吸入治疗需要气管插管和借助于呼吸机,操作相对复杂,价格昂贵,临床应用受到一定的限制;并且NO的半衰期很短,NO吸入突然中断会造成反跳性肺动脉高压。因此,寻找一种更为简单有效、价格低廉且作用时间相对长的肺动脉高压治疗方法具有临床实用价值。     

BQ123对左向右分流肺动脉高压肺组织ET-1及其受体表达的影响

内皮素1(endothelin-1，ET-1)是一种强效缩血管肽和促血管平滑肌细胞(SMC)分裂原。研究发现，BQ123，是选择性ETA受体(ETAR)的拮抗剂，可拮抗ET-1促培养的肺动脉SMC增殖、肥大作用。我们用套管连接法制作左向右分流肺动脉高压(简称肺高压)模型，研究BQ123对肺高压大鼠肺组织ET-1及其受体表达的影响。     

雾化吸入硝普钠治疗缺氧性肺动脉高压的研究进展

硝普钠(SNP)是常用的血管扩张药,具有对动静脉均衡的扩张作用,作用强而迅速,可促进血管内皮细胞和红细胞释放一氧化氮(NO),NO可使血小板及血管平滑肌的鸟苷酸环化酶激活,增加细胞内环磷酸鸟苷(cGMP)水平,导致血管平滑肌舒张,同时又通过环磷酸腺苷(cAMP)依赖的负反馈调节机制抑制内皮素-1的缩血管效应[1].     

Inhalation of nebulized nitroglycerin in dogs with experimental pulmonary hypertension induced by U46619

BACKGROUND: Pulmonary hypertension (PH) causes mortality in some congenital and acquired heart and lung diseases. However, inhalation of NO gas requires complicated and expensive instruments and elaborate preparations to avoid toxic gas administration. We tested the effectiveness and safety of inhaled nebulized nitroglycerin (Neb-NTG) in dogs with experimental PH. METHODS: Experimental PH was induced by continuous infusion of a thromboxane analog (U46619). The U46619 infusion rate was adjusted to maintain a systolic pulmonary artery pressure (PAP) at 40 mmHg in 10 anesthetized and mechanically ventilated dogs. Then, 20 micrograms/kg of NTG liquid nebulized by compressed air was inhaled. RESULTS: After infusion of U46619, the systolic, diastolic and mean PAP increased by 119%, 228% and 169%, respectively, and the systolic, diastolic and mean systemic arterial pressures (SAP) increased by 19%, 29% and 23%, respectively. The systolic pulmonary to systemic pressure ratio (Pp/Ps) and mean Pp/Ps increased by 83% and 113%, respectively, and the pulmonary vascular resistance (PVR), systemic vascular resistance (SVR) and pulmonary to systemic resistance ratio (Rp/Rs) increased by 341%, 100% and 145%, respectively. After inhalation of Neb-NTG in dogs with experimental PH, systolic, diastolic and mean PAP and PVR decreased by 25 +/- 4, 26 +/- 11, 25 +/- 9 and 31 +/- 21%, respectively. There were no significant changes in systolic, diastolic and mean SAP, SVR, cardiac output and plasma methemoglobin concentrations. The systolic and mean Pp/Ps decreased by 18 +/- 7 and 20 +/- 7%, respectively. The Rp/Rs decreased by 25 +/- 13%. CONCLUSIONS: The results of this study demonstrate that Neb-NTG is an effective and selective pulmonary vasodilator and may offer a new therapeutic option for PH.     

内源性硫化氢对大鼠高肺血流性肺动脉高压的调节作用

目的应用内源性硫化氢(hydrogensulfide,H2S)生成酶胱硫醚-γ-裂解酶(cystathionineγ-lyase,CSE)的抑制剂炔丙基甘氨酸(propargylglycine,PPG),探讨H2S在大鼠高肺血流性肺动脉高压形成中的作用。方法雄性SD大鼠25只,体重120～140g,随机分为分流组(n=9)、分流 PPG组(n=8)和假手术组(n=8)。分流组及分流 PPG组大鼠经腹主动脉—下腔静脉穿刺术建立高肺血流动物模型,分流 PPG组大鼠腹腔内注射PPG37.5mg/(kg·d),分流组与假手术组大鼠每日给予等量生理盐水。分流术后4周,采用右心导管法测量各组大鼠肺动脉平均压(meanpulmonarypressure,MPAP),用敏感硫电极法测量大鼠血浆和肺组织H2S含量,分别计算大鼠心脏组织右心室/左心室 室间隔(rightventricle/leftventricle septum,RV/LV SP)和心脏重量/体重(heartweight/baseweight,HW/BW)的值。结果分流术后4周,分流组大鼠MPAP与假手术组比较差别无显著性;分流 PPG组大鼠MPAP较分流组及假手术组分别升高了17.70%和21.79%(P<0.05);分流组血浆H2S含量比假手术组明显升高(50.12±6.13vs45.16±5.56,P<0.05);分流 PPG组大鼠血浆H2S含量明显低于分流组和假手术组(38.56±4.98vs50.12±6.13、38.56±4.98vs45.16±5.56,P均<0.05);分流 PPG组大鼠RV/LV SP和HW/BW明显高于分流组和假手术组(0.33±0.03vs0.30±0.03、0.33±0.03vs0.29±0.02,P<0.05)。结论内源性H2S在高肺血流性肺动脉高压形成过程中发挥保护性调节作用。     

The effect of nifedipine on monocrotaline-induced pulmonary hypertension in rats

Effective drug therapy for pulmonary hypertension has not yet been developed. This study was designed to estimate the long-term hemodynamic and histopathological effects of nifedipine on severe pulmonary hypertension using animal models. Injection of one dose of monocrotaline produced subacute pulmonary hypertension in 7 week old Sprague-Dawley rats. Nifedipine (10 mg/kg) was administered intraperitoneally every day. For 5 weeks, bodyweight and hemodynamic parameters were measured, and right ventricle (RV) and left ventricle with septum (LV + S) were weighed separately. Medial thickness of the small pulmonary arterial wall was calculated by Suwa's method. Compared with the control group, the increase in right ventricular systolic pressure, total pulmonary resistance index, weight ratio of RV/(LV + S) and medial hypertrophy in the nifedipine-treated rats were significantly limited without causing systemic hypotension. These results suggest that treatment with nifedipine may also be effective in attenuation of pulmonary hypertension when applied to humans.     

The effect of bunazosin on monocrotaline-induced pulmonary hypertension in rats

In order to estimate the long-term hemodynamic and histologic effects of bunazosin hydrochloride on primary pulmonary hypertension (PPH), for which effective internal therapy has not yet been proposed, we produced subacute pulmonary hypertension in 6 week old Sprague-Dawley rats by injecting one dose of monocrotaline. Bunazosin (10 mg/kg) was administered intraperitoneally every day and bodyweight and hemodynamic parameters were measured. Right ventricle (RV) and left ventricle with septum (LV + S) were weighed separately. Medial thickness of the small pulmonary artery was calculated. In the bunazosin group, the increase of right ventricular systolic pressure (RVSP) as pulmonary arterial systolic pressure and the ratio of RVSP to pulmonary flow were limited, without causing systemic hypotension, compared to the control group. Weight ratio of RV/(LV + S) had a tendency to be limited in the bunazosin group. As for medial thickness, there was no significant difference between the two groups. It may be concluded that bunazosin hydrochloride should be considered for clinical trials in treatment of PPH in humans.     

高肺血流性肺动脉高压大鼠肾上腺髓质素前体N端20肽的变化

目的：高肺血流性肺动脉高压的形成机制至今尚未完全阐明。该实验通过研究高肺血流性肺动脉高压大鼠肺组织肾上腺髓质素前体N端20肽( PAMP ) 表达以及血浆PAMP含量的变化,探讨PAMP在高肺血流性肺动脉高压形成中的作用。方法：16只雄性SD大鼠随机分为对照组和分流组,每组各8只。对分流组大鼠行腹主动脉-下腔静脉分流术。11周后,以右心导管法测定肺动脉收缩压（sPAP）、肺动脉舒张压（dPAP）和肺动脉平均压（mPAP）,观察肺动脉超微结构的变化。并且以放射免疫法测定血浆中PAMP含量,以免疫组织化学法检测肺组织中PAMP表达。结果：分流组大鼠sPAP、dPAP和mPAP均明显高于对照组（均P<0.01）。电镜下,肺腺泡内动脉内皮细胞增生、肿胀,内弹力层不规则,平滑肌细胞肥厚、向合成表型转化。并且分流组大鼠血浆PAMP含量明显高于对照组（P<0.01）,肺动脉内皮细胞和平滑肌细胞PAMP表达明显增强。结论：肺动脉和血浆PAMP表达的上调可能参与了高肺血流性肺动脉高压的形成。［中国当代儿科杂志,2007,9（6）：574-576］