先天性心脏病重度肺动脉高压性质的综合评价

目的探讨先天性心脏病（简称先心病）合并重度肺动脉高压患儿器质性肺动脉高压（简称肺高压）的诊断标准。方法３７例经手术治疗后早期肺动脉压力降至正常的患儿作为动力性肺高压组；７例经手术治疗后仍持续性肺动脉高压及６例临床诊断为器质性肺高压而未予手术的共１３例患儿作为器质性肺高压组，对比两组心导管检查血液动力学指标。结果两组肺血管阻力、肺小动脉楔压、肺循环血流量与体循环血流量之比（Ｑｐ／Ｑｓ）及降主动脉血氧饱和度（ＳａＯ２）差异均有显著意义，如按年龄大于２岁、肺动脉阻力＞７２ｋＰａ·ｓ－１·Ｌ－１（９Ｗｏｏｄ单位）、肺小动脉楔压≤１．６ｋＰａ（１２ｍｍＨｇ）、Ｑｐ／Ｑｓ＜２和动脉血氧饱和度＜０．９０作为临床诊断器质性肺高压的指标，则本组动力性肺高压组仅有５．４％的患儿符合上述指标３项或３项以上，而器质性肺高压组所有病例均符合上述指标３项或３项以上。结论先心病合并重度肺动脉高压存在上述５项指标中３项或３项以上，高度提示患儿存在器质性肺动脉高压     

内皮素在左向右分流型先天性心脏病肺动脉高压中作用的研究

为探讨内皮素在左向右分流型先天性心脏病（简称先心病）肺动脉高压（简称肺高压）中的作用，采用放射免疫法测定５２例肺高压和１１例非肺高压先心病患儿腔静脉和肺动脉血浆内皮素（ｉｒＥＴ－１）水平，并对其中１０例肺高压患儿进行肺活检免疫细胞化学染色。结果，肺高压患儿肺动脉和腔静脉血浆ｉｒＥＴ－１水平均随肺动脉压力升高而增加，并高于非肺高压患儿（Ｆ＝２．９５；３．３９，Ｐ＜０．０５）。肺高压患儿血浆ｉｒＥＴ－１与肺动脉压力及阻力成正相关（ｒ＝０．６５；０．５８，Ｐ＜０．０１）。肺高压患儿肌性和弹性肺小动脉ｉｒＥＴ－１染色明显加深。研究提示，左向右分流型先心病患儿内皮素产生的增加可导致肺高压患儿肺血管的中膜肥厚和内膜增生，促进了肺高压的发展。     

韧粘素在先天性心脏病合并肺高压患儿肺血管中的表达

为探讨韧粘素（ＴＮ）在先天性心脏病（先心病）合并肺高压发病机制中的作用及其其调节因素，采用免疫组化方法观察不同肺血清和／或不同肺动脉压力下，先心病患儿肺小动脉中ＴＮ的表达情况。图像分析结果表明，高肺血流伴肺高压时ＴＮ表达阳性面积比例明显高于高肺血流不伴肺高压和对照组（Ｐ均〈０．０１），ＴＮ表达与肺动脉压力升高显著相关（ｒ＝０．７５，Ｐ〈０．０１），与肺血流增多无关（ｒ＝－０．４８，Ｐ〉０．０５）。     

先天性心脏病合并肺动脉高压患儿肺血管中维甲酸受体表达的变化

目的 通过观察不同肺血流和(或)肺动脉压力情况下先天性心脏病(先心病)患儿手术时活检肺组织中肺血管维甲酸受体(RARα、β、γ亚型)的表达情况,探讨其在先心病合并肺动脉高压发病机制中的可能作用.方法 收集先心病及非先心病患儿开胸手术病例共31例,其中无高肺血流及肺动脉高压的非先心病手术对照组病例6例;左向右分流先心病高肺血流组7例;左向右分流先心病肺动脉高压组18例.手术时取右下肺组织,连续切片后采用小鼠抗人RARα、β、γ亚型单克隆抗体进行免疫组化显色,图像分析观察三种血型相对表达面积,同时分析其与肺高压组肺动脉压力、HE病理分级的相关性.结果 肺动脉高压组肺动脉中RAR α、β、γ亚型阳性表达面积均较对照组及高肺血流组明显减少(P均<0.01),而对照组与高肺血流组之间差别无统计学意义(P>0.05);肺高压组RAR各亚型相对表达面积与肺动脉压力无相关性(r=0.03～0.42,P均>0.05);RARα、β表达与HE病理分级有相关性(r=0.59、0.52,P均<0.01),RARγ与HE病理分组无相关性(r=0.21,P>0.05).结论 先心病合并肺动脉高压时肺动脉中RAR各亚型表达均有减少,且RARα、β表达减少随肺血管病变程度加重而愈加明显,提示RAR可能参与了先心病肺动脉高压的肺血管重建过程.     

先天性心脏病合并肺动脉高压时肺组织病理与免疫组化研究

为探究先天性心脏病（先心病）伴肺动脉高压（肺高压，PH）患儿肺组织一氧化氮合酶（eNOS)的表达有否改变，随机选择法洛四联症（tetralogy of Fallot,TOF)、单纯室间隔缺损(ventricular septal defect,VSD)/房间隔缺损（atrial septal defect,ASD)、先心病合并PH患儿48例，分成3组，取少许右肺中叶组织，利用免疫组织化学法对eNOS进行半定量分析。结果显示先心病伴PH组患儿肺组织内皮细胞内的eNOS染色明显弱于TOF组和单纯VSD／ASD组患儿（P＜0．01）。提示先心病PH组肺组织的eNOS含量水平低下，造成内源性NO生成减少，为临床吸入NO治疗PH提供了理论依据。     

先天性心脏病肺动脉高压患儿肺组织内皮素-1与胶原合成关系的研究

目的研究左向右分流先心病肺动脉高压(肺高压)患儿肺组织内皮素-1(ET-1)与肺组织Ⅰ、Ⅲ型胶原合成的关系,探讨左向右分流先心病患儿肺高压形成的机理。方法选择左向右分流先心病患儿18例,根据肺动脉收缩压分为肺高压组(n=10),非肺高压组(n=8)。所有患儿在外科手术体外循环开始前,取右肺中叶组织(1cm×1cm×1cm),放射免疫法测定患儿血浆及肺组织ET-1含量;RT-PCR法检测肺组织Ⅰ、Ⅲ型胶原mRNA表达。结果先心病肺高压患儿血浆及肺组织ET-1含量明显高于肺动脉压正常者(P<0.01)。肺高压患儿肺组织Ⅰ、Ⅲ型前胶原mRNA的表达与肺动脉压正常者相比明显增加(P<0.05)。结论ET-1可能通过刺激肺动脉平滑肌细胞胶原合成增加参与肺高压的形成。     

弹性蛋白酶抑制剂对肺动脉平滑肌细胞增殖和凋亡的影响

目的探讨弹性蛋白酶抑制剂对肺动脉平滑肌细胞增殖和凋亡的影响。方法利用野百合碱建立大鼠肺高压模型。21d后,治疗组予ZD-0892管饲,剂量按240mg/(kg·d)分2次给予,模型组按同样剂量管饲ZD-0892的溶媒;而正常对照组管饲同样剂量的生理盐水。于实验28d,采用荧光分光光度计检测肺动脉弹性蛋白酶活性,采用免疫组化方法检测肺小动脉内韧粘素(tenascin,TN)的表达和细胞增殖的情况,并采用原位缺口末端标记法检测肺小动脉内细胞凋亡的情况。结果模型组大鼠肺动脉弹性蛋白酶的活性明显增高,肺组织内TN的表达较正常组明显增强,增生指数显著上升而凋亡指数显著下降;治疗组大鼠肺动脉弹性蛋白酶活性明显减低,肺组织内TN表达较模型组明显减弱,增生指数显著下降而凋亡指数显著上升。结论ZD-0892能抑制血管平滑肌细胞(vascularsmoothmusclecell,VSMC)的增生,诱导VSMC的凋亡,最终使野百合碱诱导的严重肺高压完全逆转。     

不伴体-肺动脉侧支的婴幼儿肺血减少型复杂先心病肺动脉发育程度的对比观察

目的 分析不伴体-肺动脉侧支的婴幼儿肺血减少型复杂先心病肺细小动脉结构，与左、右肺动脉的发育进行对照。方法 46例不伴体-肺动脉侧支的肺血减少型复杂先心病婴幼儿为病变组。对照组为同年龄组非心、肺源性疾病死亡患儿肺组织标本5例。形态半定量测量肺细小动脉平均中膜厚度百分比（MT％）、平均中膜面积百分比（MS％）和单位面积肺细小动脉数目（APSC）。结果 二组APSC的差异有统计学意义（P=0．007）。心血管造影测量的左、右肺动脉直径之间以及APSC与McGoon比值、肺动脉指数之间呈正相关性。结论 不伴体-肺动脉侧支的肺血减少型复杂先心病婴幼儿肺细小动脉的发育程度与中心肺动脉的发育程度具有良好的相关性。     

内皮素-1和von Willebrand因子在室间隔缺损并肺动脉高压患儿肺血管的表达及意义

目的观察室间隔缺损（VSD）并肺动脉高压（PH）患儿内皮素-1（ET-1）与von Willebrand因子（vWF）在肺血管内膜表达的差异，探讨两者在PH发生发展及肺血管重建中的作用。方法VSD无PH患儿10例为对照组；VSD并PH患儿20例为PH组（PH组），根据肺动脉平均压分为中度PH组（Ⅰ组）和重度PH组（Ⅱ组）。取右肺中叶肺组织，免疫组织化学染色，测光密度值。结果肺小动脉vWF、ET-1表达在对照组与PH组、对照组与Ⅰ组、对照组与Ⅱ组、Ⅰ组与Ⅱ组之间，均有显著性差异（P均〈0．01）；而肺小静脉vwF、ET-1表达均无统计学差异（P〉0．05）。同组别肺小动脉与肺小静脉vwF、ET-1表达有显著性差异（P均〈0．01）。ET-1、vWF、肺动脉平均压、VSD直径与主动脉直径之比四者间相互呈正相关（P〈0．01，0．05）。结论ET-1及vWF与PH的发生发展、肺血管重建有关。肺组织中ET-1的主要来源可能是肺小动脉。     

血管形成因子- 1与肺动脉高压形成关系的研究

目的了解血管形成因子-1(Angpt-1)与肺动脉高压(PH)形成的关系。方法收集11例存在PH的先天性心脏病(先心病)患儿的肺组织,应用荧光定量PCR法分析Angpt-1mRNA的表达率,免疫组化技术分析Angpt-1蛋白的表达;并将11例先心病伴肺高血流患儿和6例正常儿童肺组织进行比较。结果PH患儿和肺高血流组患儿肺组织中Angpt-1mRNA的表达率和Angpt-1蛋白的表达均高于正常组(P<0.01)。结论Angpt-1参与和促进先心病肺动脉高压的发生和发展。     

�ڷ���������Ԥ���Ҽ��ȱ�𲢷��ζ�����ѹ�ٴ���Ч�о�

??Objective??To explore the preventive effect of regular doses of captopril on the pulmonary arterial hypertension associated with ventricular septal defect??VSD?? and its mechanism. Methods??Forty cases of children with VSD in accordance with the inclusive criteria??who were hospitalized in Chengdu Women and Children’s Central Hospital from July 2013 to July 2015 ??were collected and randomly divided into blank control group??n??20??and captopril intervention group??n??20??. Plasma MMP-9 and TIMP-1 were examined by using ELISA??and PASP??the Qp/Qs and right ventricular Tei index were measured by cardiac color Doppler ultrasound at 0 week??1 week??4 weeks??8 weeks??and 12 weeks respectively??side effects in captopril intervention group were also observed. Results??PASP??the Qp/Qs??right ventricular Tei index??plasma MMP-9 and TIMP-1 level in blank control group were increased over time??the same indexes in captopril intervention group were decreased??the changing trend of two groups had statistically significant difference??all P??0.05??. The indexes were of no difference between the two groups at 0 week??all P??0.05????PASP and right ventricular Tei index in captopril intervention group were lower than blank control group at 1 week??4 weeks??8 weeks??and 12 weeks??all P??0.05????the Qp/Qs plasma??MMP - 9 and TIMP - 1 level in captopril intervention group were lower at 4 weeks??8 weeks??and 12 weeks??all P??0.05??. No side effects were found in captopril intervention group during follow-up. Conclusion??Oral regular doses of captopril in the VSD children undergoing elective surgery may reduce pulmonary vascular remodeling and prevent pulmonary hypertension in order to achieve the best age at surgery??one of the mechanisms might be improving indexes of PASP??right ventricular Tei index and the Qp/Qs by reducing the plasma MMP 9 and TIMP - 1 level.     

Serum Level of Soluble Intercellular Adhesion Molecule-1 Correlates with Pulmonary Arterial Pressure in Children with Congenital Heart Disease

Background  Endothelial activation and vascular inflammation are thought to be the mechanisms of pulmonary hypertension. Increased expression of the intercellular adhesion molecule (ICAM-1) and raised serum level of its soluble form (sICAM-1) are found in various conditions associated with endothelial activation. Methods  Serum samples from 31 children (14 boys and 17 girls; age, 4.9 ± 4.6 years) with congenital heart disease (CHD) collected at the time of cardiac catheterization were analyzed for sICAM-1 level. Uni- and multivariable stepwise linear regression analyses were performed for the following variables against the sICAM-1 level: age, hemoglobin, serum creatinine, systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), pulmonary blood flow (Qp) and resistance (Rp), systemic blood flow (Qs) and resistance (Rs), Qp/Qs, Rp/Rs, and pulmonary and systemic oxygen saturation. Results   The sICAM-1 levels in children who had CHD with and without pulmonary hypertension were 411 ± 110 and 344 ± 81 ng/ml, respectively (p = 0.11). In the univariable models, age, serum creatinine, systolic PAP, mean PAP, diastolic PAP, Rp, and Rp/Rs were significantly correlated with sICAM-1 level. In the multiple stepwise regression model, only mean PAP remained as an independent predictor of sICAM-1 level (r = 0.55; p = 0.002). Conclusion  Children with CHD and pulmonary hypertension had a trend toward elevated sICAM-1 compared with CHD children who had no pulmonary hypertension. A linear correlation was found between mean pulmonary arterial pressure and sICAM-1 level.     

Effect of beraprost sodium on pulmonaryvascular resistance in candidates for a Fontan procedure: A preliminarystudy

OBJECTIVE: Although long-term prostacyclin(PGI2) therapy in patients with severe pulmonary hypertension (PH)reduces pulmonary vascular resistance (PVR), there have been no reports on its therapeutic effects in patients with mild PH. We investigated the chronic effect of beraprost sodium (BPS), an oral PGI2 analog, in children with mild PH. METHODS: We studied 20 patients who were destined for a Fontan procedure with a mean pulmonary arterial pressure(PAP) of>20 mmHg and/or PVR of>3.0 Wood units. Both the PAP and the PVR in these cases were too high for patients to undergo a successful Fontan procedure. Seven patients received BPS (PG group) and 13 did not (control group). All patients underwent repeat cardiac catheterization to examine pulmonary hemodynamics. RESULTS: In the PG group, the pulmonary-to-systemic flow ratio (Qp/Qs) did not change after BPS administration(1.1 +/- 0.6 vs 1.3 +/- 0.9);however, the mean PAP decreased significantly (25.3 +/- 8.2 vs 19.9 +/- 6.5 mmHg; P < 0.05),as did PVR (3.7 +/- 1.3 vs 2.3 +/- 0.9 Wood units; P < 0.05), whereas the pulmonary artery (PA) index increased significantly (312 +/- 136 vs 375 +/- 165; P < 0.05). In the control group, the mean PAP decreased significantly (24.9 +/- 4.7 vs 19.8 +/- 6.3 mmHg; P < 0.05)and the PA index increased significantly (295 +/- 72 vs 362 +/- 114; P < 0.05). No significant changes in Qp/Qs (1.5 +/- 0.8 vs 1.4 +/- 0.6)or PVR (2.9 +/- 1.3 vs 2.5 +/- 0.8 Wood units) were observed. CONCLUSION: We conclude that long-term BPS administration probably reduces PVR in potential candidates for a Fontan procedure with mild PH. This treatment would reduce the risks associated with the Fontan procedure and would also improve its outcome.     

����������ǰ���ض�����С�����������ಡ�ϲ��ζ�����ѹ���ʵļ�ֵ�о�

目的 探讨雾化吸入伊洛前列素进行急性血管扩张试验的价值.方法 研究对象为2007年2月至2008年5月在广东省心血管病研究所住院的50例先天性心脏病合并肺动脉高压患儿,对所有患儿进行左右心导管检查,之后肺动脉内注射酚妥拉明或雾化吸入伊洛前列素进行急性血管扩张试验,试验后重复左右心导管检查.根据Fick公式计算血流动力学参数.综合判断肺动脉高压性质,将惠几分成两组:动力组和梗阻组.动力组患儿进行手术治疗,术后定期随访并修正术前诊断.结果 酚妥拉明会显著增高受试者的心率,而伊洛前列素对心率的影响较轻微;酚妥拉明和伊洛前列素都能够降低平均肺动脉压力和肺血管阻力,升高肺循环血流量;酚妥拉明同时会降低平均主动脉压力和体循环阻力,升高体循环血流量,而伊洛前列素对体循环没有明显的影响.在使用伊洛前列素的急性血管扩张试验中,平均肺动脉压力、肺血管阻力/体循环阻力和肺循环血流量/体循环血流量等参数的变化在动力组和梗阻组中差异无统计学意义(P值分别为0.016、0.024和0.030).而使用酚妥拉明的急性血管扩张试验中,平均肺动脉压力和肺血管阻力两项参数的变化在动力组和梗阻组中差异有统计学意义(P值分别为0.017和0.004).结论 在先天性心脏病合并肺动脉高压的患儿中,使用酚妥拉明或伊洛前列素进行急性血管扩张试验都能够有效区分动力性与梗阻性肺动脉高压.酚妥拉明用药前后,肺循环和体循环的压力、阻力和血流量都有明显变化.而伊洛前列素雾化吸入以影响肺循环为主,可以保持相对平稳的血流动力学,在安全性上优于酚妥拉明.     

西地那非抑制高肺血流肺动脉高压大鼠肺血管重构和上调肺血管Kv1.5mRNA表达

目的 观察高肺血流肺动脉高压大鼠肺血管结构重建和肺血管电压依从钾通道Kv1.5mRNA表达变化,探讨口服西地那非对高肺血流肺动脉高压大鼠肺血管重构及肺血管电压依从钾通道Kv1.5mRNA表达的影响.方法 将27只雄性SD大鼠随机分为对照组(n=9)、分流组(n=9)、分流+西地那非组(n=9).后两组大鼠通过腹主动脉一下腔静脉分流术建立高肺血流肺动脉高压动物模型.对分流+西地那非组大鼠每天灌胃枸橼酸西地那非10 mg·kg-1·d-1,对照组和分流组每天灌胃等量生理盐水.11周后,测定肺动脉平均压(mPAP)及肺动脉收缩压(sPAP);观察右室肥厚程度,计算右室重量/(左室+室间隔)重量比值,以[RV/(LV+S)]表示;计算肺中、小血管肌型动脉相对中膜厚度(RMT);采用实时荧光RT-PCR定量法观察大鼠肺血管电压依从钾通道Kv1.5mRNA表达.结果 与对照组比较,分流组大鼠mPAP、sPAP、RV/(Lv+S)比值显著增高(P<0.01),RMT显著增加(P<0.01),肺血管Kv1.5mRNA表达水平显著降低(P<0.01).与分流组相比,分流+西地那非组mPAP、sPAP、RV/(LV+S)比值显著低于分流组(P<0.01),RMT显著降低(P<0.01),肺血管Kv1.5mRNA表达水平显著升高(P<0.01).分流+西地那非组mPAP、sPAP、RV/(Lv+S)比值和RMT与对照组比较,差异均无显著性意义(P>0.05);两组大鼠Kv1.5 mRNA表达水平也无显著性差异(P>0.05).结论 高肺血流肺高压大鼠肺血管发生重构并且其肺血管Kv1.5mRNA表达下降,而口服枸橼酸西地那非抑制高肺血流肺高压大鼠肺血管重构和上调肺血管Kv1.5mRNA表达.     

Gene transfer of vascular endothelial growth factor reduces bleomycin-induced pulmonary hypertension in immature rabbits

BACKGROUND: The purpose of the present paper was to investigate the effect of gene transfer of vascular endothelial growth factor (VEGF) on bleomycin (BLM)-induced pulmonary hypertension in immature rabbits. METHODS: Immature rabbits (1 month old) were divided into control group (intratracheal injection of normal saline), BLM group (intratracheal injection of BLM), liposome group (intratracheal injection of BLM and liposomes) and the trans-gene group (intratracheal injection of BLM and DNA-liposome complex). The pulmonary arterial pressure (PAP) were measured by microcatheter, the pathological changes and the expression of VEGFmRNA and endothelial nitric oxide synthase (eNOS) mRNA of endothelial cells in pulmonary arteries were evaluated by hematoxylin-eosin (HE) and in situ hybridization. RESULTS: The PAP of the BLM and liposome groups were higher than the PAP of the control and trans-gene groups. The thickness of wall increased and the cavity became narrow, and thickness index and area index increased in mid- and small-sized pulmonary arteries of the BLM and liposome groups. VEGF trans-gene was able to reduce those changes; the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in the BLM and liposome groups. The level of VEGFmRNA expression in the trans-gene group was higher than that in the BLM and liposome groups, but lower than that in the control group. CONCLUSION: The PAP was elevated, the thickness of wall increased and the cavity became narrow in mid- and small-sized pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbits after 2 weeks of intratracheal injection of 4 units/kg BLM. VEGF trans-gene could reduce those changes.     

Two-Dimensional Pulsed Doppler Echocardiographic Technique for Estimating Pulmonary to Systemic Blood Flow Ratio in Children with Atrial Septal Defect and Patent Ductus Arteriosus

A two-dimensional pulsed Doppler echocardiographic method was evaluated for quantifying the pulmonary (Qp) to systemic (Qs) blood flow ratio. Twenty six patients were studied, 15 with atrial septal defect (ASD) and 11 with patent ductus arteriosus (PDA). An apical fourchamber view was used to measure the maximal Doppler flow velocities in the right and left ventricular inflow regions (RVIR and LVIR) and the maximal diameters of the tricuspid and mitral anuli at diastole. The two-dimensional pulsed Doppler pulmonary to systemic blood flow ratio (Qp/Qs) estimation involved calculating the area of the Doppler flow velocity signal along the time scale multiplied by the diameter of either the tricuspid or mitral anulus as measured on the apical fourchamber view. In ASD patients, Qp was measured at RVIR and Qs at LVIR. In PDA patients, Qp was calculated at LVIR and Qs at RVIR. Twenty-six healthy children comprised the control group. The areas of the Doppler flow velocity signals along the time scales of RVIR and LVIR were also quantified and the diameters of the tricuspid and mitral anuli were measured. In the control group, the linear correlation of the trans-mitral M(d)*M(a) to trans-tricuspid T(d)*T(a) value was r=0.909, n=26. The correlations between Doppler Qp/Qs ratio estimates and those obtained at cardiac catheterization were r=0.902, n=15 in ASD and r=0.967, n=l l in PDA. These results suggest a clinical application of this Doppler echocardiographic method in the noninvasive estimation of the cardiac shunt in ASD and PDA.     

RhoA/Rho激酶在高肺血流肺血管结构重构中的表达及其活性研究

目的探讨RhA／Rho激酶在高肺血流所致肺血管结构重构过程中所起的作用。方法108只4周龄Wistar大鼠随机分到4个分流组、4个对照组,分流组大鼠接受左侧颈总动脉-颈外静脉分流术,对照组大鼠作假手术。在术后1、2、4、8周,分别测量右心室收缩压,作血气分析计算Qp／Qs。肺组织切片HE染色光镜下观察肺血管形态学改变,测量并计算中等血管中膜厚度所占管径百分比（MT％）。免疫组化增殖细胞核抗原（PCNA）染色分析平滑肌细胞增生情况。用TUNEL细胞凋亡标记分析平滑肌细胞凋亡状况。pulldownassay分析RhoA活性,Westernblot检测RhoA、Rho激酶（ROCK2）的蛋白表达以及MYPT1磷酸化程度量化分析Rho激酶活性。结果颈总动脉-颈外静脉分流导致肺循环血流量增加,Qp／Qs平均值为2．26±0．35。分流组RVSP在术后1周和8周较对照组高（t=8．799,t=5．332,P〈0．01）。与对照组相比,分流组以平滑肌细胞过度增生和肥大为特征的中等肺动脉中膜增厚,MT％升高在第4周开始出现,到第8周更为明显（t=9．192,t=11．185,P〈0．01）。分流组PCNA阳性平滑肌细胞在第1周显著升高,第2周达最高值,与对照组相比,差异有统计学意义（t=7．213,P〈0．01）,到第4周下降到显著低于对照组（t=4．183,P〈0．01）,并持续降低,到第8周几乎观察不到增生的平滑肌细胞（t=6．152,P〈0．01）。TUNEL阳性平滑肌细胞在第2周较对照组低（t=2．418,P〈0．05）,并持续降低,到第8周几乎观察不到凋亡的平滑肌细胞（t=4．582,P〈0．01）。RhoA和ROCK2表达在第1周即高于对照组（t=6．056,t=8．411,P〈0．01）,第2周达高峰（t=9．342,t=10．437,P〈0．01）。到第4开始下降,但是到第8周仍然显著高于对照组（t=4．743,t=4．455,P〈0．01）。RhoA和Rho激酶活性在第1周也显著高于对照组（t=10．246,t=19．110,P〈0．01）,到第4周达高峰（t=24．984,t=16．124,P〈0．01）,然后开始降低,但是二者到第8周仍然显著高于对照组水平（t=4．934,t=10．426,P〈0．01）。结论在高肺血流所致的大鼠肺血管收缩和结构重构与RhoA／Rho激酶的表达和活性增强有关。     

先天性心脏病并肺动脉高压患儿血浆一氧化氮和硫化氢的变化

目的研究先天性心脏病(CHD)并肺动脉高压(PH)患者血浆一氧化氮(NO)和硫化氢(H2S)的变化及其与PH相关性,探论PH的形成机制,为临床有效治疗PH提供新的思路和理论依据。方法对全部研究对象行彩色超声心动图检查,明确CHD类型并测定肺动脉收缩压。按彩色超声心动图结果分为4组。正常儿童25例,CHD 75例,其中无PH 25例,轻度PH 25例,中、重度肺PH 25例。取CHD组术前静脉血4 mL,迅速分离血浆,采用分光光度法测定血浆NO水平,采用敏感硫电极法测定H2S水平。结果CHD患儿血浆NO水平明显高于对照组,但血浆NO水平增加到一定程度后不再随肺动脉收缩压增加而增加,肺动脉收缩压与血浆NO水平无相关性。CHD并中重度PH组血浆H2S水平明显低于CHD并轻度CHD组,CHD并轻度PH组血浆H2S水平明显低于对照组,肺动脉收缩压与血浆H2S水平呈负相关。结论CHD致PH形成时NO水平升高,代偿性内源性NO上调可能对缓解PH起一定作用。CHD致PH形成时H2S明显降低,内源性H2S下调可能在PH形成中起重要的作用。