吸烟引起肺细小动脉病理改变的图像定量分析

为更深层次的了解吸烟对肺细小动脉的影响，在原６００例肺标本中，按年龄及吸烟指数分成２１分组的观察基础上，每分组不加选择地取４例，共８４例，每例２张切片，用图像分析仪测试切片中，所有的较圆整的＜２００μｍ肺细小动脉。测试５个指标：血管腔面积、总面积、壁面积和外径及壁厚。经计算机处理：腔面积／总面积（ＥＡ／ＴＡ）、壁面积／总面积（ＷＡ／ＴＡ）、壁厚／外径（ＷＤ／ＴＤ）三个相对比值。经统计学处理，结果ＥＡ／ＴＡ、ＷＡ／ＴＡ、ＷＤ／ＴＤ经Ｆ及Ｑ检验，两两比较，轻度吸烟与不吸烟组年龄组比无明显差异（Ｐ＞０．０５）；而中度吸烟以后与不吸烟、轻度吸烟各相应年龄组比有非常显著的差异（Ｐ＜０．０１）。且在４１岁组以后６０￣２００μｍ肺细动脉和５１岁以后＜６０μｍ肺细动脉差异更显。表明吸烟量对血管刺激随年龄的增长而增强，虽然各组中因年龄增长血管改变有所增加，但无显著性差异。这些阻力型肺细小动脉壁增厚是肺动脉高压形态学基础，持续加大可使血供发生改变，影响气体交换和血液动力学及血液流变学改变，从而右心负荷加重，可导致肺心病。对于４０岁以后吸烟者应予戒烟。

HYPOXIA AND ENDOTHELIN－1 STIMULATE DNA SYNTHESIS OF PULMONARY ARTERY SMOOTH MUSCLE CELLS

Hypoxia and endothelin-1 (ET-1) are associated with constriction of pulmonary vasculature both in vivo and in vitro. However, the role of hypoxia and ET-1 in the vascular remodelling during the development of pulmonary hypertension is unclear. This study demonstrated that ET-1(0. 1 nmol/L to 100 nmol/L) increased the [￣3H]thymidine uptake in a dose-dependent manner in cultured bovine pulmonary artery smooth muscle cells(PASMC). which was enhanced by exposing PASMC to hypoxia (2%O2, 93%N2,5%CO2 ). BQ123, the specific antagonist of endothelin receptor subtype A,eliminated the ET-1 medicated proliferation of PASMC and the cooperative effect of hypoxia. Some dilatory drugs could inhibite the mitogenic effect of ET-1. We also observed that hypoxia significantly increased [￣3H] thymidine uptake in PASMC without ET-1 and BQ123 could inhibite this effect. Radioimmunoassay suggested that there was an autocrine of ET-1 in cultured PASMC which was enhanced by hypoxia significantly.

INCREASED EXPRESSION OF PDGF AND C-MYC GENES IN LUNGS AND PULMONARY ARTERIES OF PULMONARY HYPERTENSIVE RATS INDUCED BY HYPOXIA

The role of growth factors and proto-oncogene in pulmonary vascular structural remodelling is not well known.The present study examined gene expression of platelet-derived growth factor(PDGF)-A and -B chain and proto-oncogene,c-myc,in lung tissue and pulmonary artery of rats exposed to hypoxia and compared to those levels of gene expression in normal rats.Normal lungs and pulmonary artery expressed PDGF-A chain transcript of 1.7 kb and PDGF-B chain transcript of 3.5 Kb.The c-myc transcript of 2.2 kb was expressed as well. After hypoxic exposure for 7 and 14 days mRNA levels of PDGF-B chain and cmyc were elevated significantly compared with those of control rats.PDGF-A chain mRNA increased after hypoxia for 7 days,and then declined.These results suggest that activation of autocrine and/or paracrine is important in proliferation mechanism of pulmonary artery smooth muscle cells in hypoxic pulmonary hypertensive rats.

Pulmonary embolism after transcatheter arterial chemoembolization for hepatocellular carcinoma:a retrospective analysis on 10 years' experience

To study the clinical characteristics and treatment of pulmonary embolism （PE） after transcatheter arterial chemoembolization （TACE） for hepatocellular carcinoma （HCC）. Methods： The clinical records of 13 512 patients diagnosed with HCC and received TACE from January 2000 to December 2009 were reviewed. Among these patients, 5 031 were allocated into group A who had one or more disorders like diabetes, hypertension, coronary heart disease, obesity or varicose vein of lower limb, while the other 8 481 patients who did not have such disorders were in group B. Results： A total of 39 185 TACE procedures were performed for the 13 512 patients. Five （0.01%） patients in group A developed PE after TACE, of whom two recovered 4 and 5 d later with early anticoagulant therapy while the hypertension, coronary heart disease, obesity or varicose vein of lower limb are possibly more likely to develop PE other 3 died of respiratory failure within 5 h. The mortality of PE was 60% （3/5）. Conelusion： HCC patients with diabetes, after TACE than those without such disorders. Patients who have such disorders should be more carefully observed after TACE and early treatment with heparin should be applied once PE develops.

Prevalence of Anti-endothelial Cell Antibodies in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases

Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure

Background Sleep-disordered breathing （SDB） is known to occur frequently in and may predict worsening progression of patients with congestive heart failure （CHF）. SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyper- tension （PAH） via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin （OPG） and endothelial progenitor cells （EPCs）. The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAIl. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB （n = 52）, or without SDB （n - 68）. OPG and N-terminal pro-brain natriuretic peptide （NT-proBNP） from each group was analyzed and cor- related with EPCs and the mean pulmonary artery pressure （mPAP） measured by right heart catheterization. Results A significant decrease in circulating EPCs （29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/x 200 field; P 〈 0.05） was found in CHF patients with SDB compared to those without SDB. Both OPG （789.83 ±89.38 vs. 551.29 ± 42.12 pg/mL; P 〈 0.05） and NT-proBNP （5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P 〈 0.05） were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP （50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P 〈 0.05）. EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour （RDI, r = -0.45, P = 0.037） and blood level of OPG （r =-0.53, P = 0.011）. Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RD1. Conclusions SDBdue to hypoxemia from decompensated CHF is associated with （1） OPG elevation, （2） EPC depletion, and （3） mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.

EFFECT OF HYPOXIA ON DNA SYNTHESIS AND C－MYC GENE EXPRESSION OF PULMONARY ARTERY SMOOTH MUSCLE CELLS

The neonate is particularly susceptible to the development of hypoxic pulmonary hypertension. The present study was undertaken to observe the effect of hypoxia on DNA synthesis and c-myc gene expression between newborn calf and adult bovine PASMC in vilro. DNA synthesis measured by 3H- TdR incorporation was increased after hypoxic challenge for 24h. Hypoxia enhanced the increment in 3H-TdR incorporation induced by EGF. Northern blot analysis revealed that PASMC cultured in both normoxia and hypoxia expressed c- myc gene transcript of 2. 2Kb ,but there is a higher 2. 2Kb mRNA expression in hypoxic PASMC than that in normoxia. We speculate that newborn calf PASMC exhibited potential response to hypoxia than adult,which was augmented by EGF. Enhanced c-myc gene expression may lead to a great understanding of the mechanism of PASMC growth in the development of pulmonary hypertension.

Effects of NHE-1 ribozyme gene transfection on apoptosis of rat pulmonary artery smooth muscle cells in vitro

Objective : To investigate the effects of the transfection of NHE-1 ribozyme gene on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in vitro. Methods: After NHE-1 ribozyme gene was designed, synthesized and then cloned into plasmid pLXSN, the recombined plasmid was tansfected into cultured rat PASMC. Expression of NHE-1 mRNA was detected with semi-quantitative RT-PCR. Intracellular pH (pHi) was measured by using fluorescence dye BCECF-AM. Cell cycle was measured with aid of flow cy-tometric DNA analysis. Cell apoptosis was observed with electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNED respectively. Results: The NHE-1 mRNA expression level and pHi value were significantly lower in PASMCs transfected with NHE-1 ribozyme gene than those transfected with pLXSN or without transfection. Meanwhile, the apoptosis rate of cells transfected with NHE-1 ribozyme gene was increased significantly. Morphology of cell apoptosis was observed in the cells transfected with NHE-1 ribozyme gene under an electron microscope. Conclusion: The transfection of NHE-1 ribozyme gene induces the apoptosis of PASMCs by inhibiting NHE-1 expression and intracellular acidification.

Novel therapy for idiopathic pulmonary arterial hypertension： Can hepatocyte growth factor be beneficial？

Idiopathic pulmonary arterial hypertension （IPAH） is a progressive, nearly fatal condition that until recently has had very few treatment options. Median survival time for untreated IPAH was 2.8 years without effective drug intervention. IPAH is characterized by deregulated proliferation of pulmonary arterial endothelial and intimal smooth muscle cells resulting in progressive pulmonary vascular remodeling and an increase in pulmonary arterial pressure. In order to alleviate their symptoms, anticoagulants, diuretics, calcium channel blockers and inotropic agents have been used to treat patients with PAH. Moreover, specific targeted therapies using prostacyclins,

Roles of NHE-1 in the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats

Objective To evaluate the roles of Na +/H + exchanger-1 (NHE-1)in the proliferation and apoptosis of pulmonary artery smooth muscle cells in rats. Methods Twenty Wistar rats were randomized into control group and 3-week hypoxic group. Intracellular pH (pHi) of the smooth muscle was determined with fluorescence measurement of the pH-sensitive dye BCECF-AM, and the expression of NHE-1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Primary culture of pulmonary artery smooth muscle cells in vitro was performed. In situ cell death detection kit (TUNEL) was used for studying the effect of specific NHE-1 inhibitor-dimethyl amiloride (DMA) on the apoptosis of muscle cells which had intracellular acidification. Results pHi value and NHE-1 mRNA expression of pulmonary artery smooth muscle cells were significantly higher in the hypoxic group than in the control group (P【0.01, P【0.001). DMA elevated the apoptotic ratio remarkably. The effect was enhanced when DMA concentration increased and the time prolonged.Conclusions With the function of adjusting pHi, NHE-1 may play an important role in the proliferation and apoptosis of pulmonary artery smooth muscle cells.