血小板活化因子在幼年大鼠肠道免疫屏障功能损伤中的作用

目的：胃肠功能障碍与严重感染引起的肠屏障功能破坏密切相关。血小板活化因子(plateletactivatingfactor,PAF)可引起肠损伤。该文应用PAF受体拮抗剂研究PAF对幼年大鼠肠黏膜免疫屏障功能损伤作用。方法：18日龄Wistar大鼠,随机分为LPS组和PAF受体拮抗剂组(预防组和治疗组)及对照组。LPS组和对照组分别腹腔注射内毒素5mg/kg及生理盐水1mL/kg,每一时相点8只,分别于注射后1.5,3,6,24,48,72h取回肠。预防组和治疗组分别于每一时相点注射LPS前、后30min腹腔注射PAF受体拮抗剂BN520215mg/kg。应用双抗体PEG放免法测定肠黏膜中分泌型IgA(secretoryIgA,sIgA)含量。苏木精伊红染色作形态学检查,并称湿(W)干(D)重,按照WD/W,以其%计算湿干比。结果：1.5,3,6,24hLPS组可见回肠绒毛水肿,固有层血管充血,间质淋巴管扩张,肠腔炎性渗出,拮抗剂组仅见绒毛水肿。实验组各时相点湿干比均较对照组升高,拮抗剂组较LPS组略低。LPS组1.5,3,6,24,48hsIgA均较对照组明显降低P<0.01。拮抗剂组各时相点sIgA均较LPS组高,预防组较治疗组sIgA略低。结论：PAF在肠黏膜的免疫屏障功能损伤中起一定作用,预防和治疗性应用PAF受体拮抗剂BN52021可减轻肠损伤。     

血小板活化因子受体拮抗剂对内毒素血症幼年大鼠肠道黏液蛋白损伤的作用

目的 探讨血小板活化因子(PAF)受体拮抗剂在内毒素血症幼年大鼠肠道黏液蛋白(MUC2)损伤中的作用.方法 18日龄Wistar大鼠,随机分为对照组和实验组,实验组又分为内毒素组(LPS组)、PAF受体拮抗剂预防组(简称预防组)和PAF受体拮抗剂治疗组(简称治疗组),每一时点(注射LPS后1.5、3、6、24、48、72 h)各8只,注射LPS后1.5、3、6、24、48、72 h取回肠.LPS组和对照组分别腹腔注射内毒素5 mg/kg及生理盐水lⅡd/J‘g;预防组于注射LPS前30 min、治疗组于注射LPS后30 min腹腔注射PAF受体拮抗剂BN52021 5 ng/kg.用透射电镜做形态学检查.应用免疫组化方法检测肠黏膜中MUC2变化.结果 电镜下对照组肠微绒毛及细胞间紧密连接未见异常.LPS 组上皮细胞连接增宽;微绒毛变细、稀疏,部分断裂、脱落;细胞器受损.预防组和治疗组改变较LPS组轻.对照组MUG2蛋白均匀地分布于回肠上皮细胞表面,MUC2蛋白染色阳性的杯状细胞轻度膨胀、扩张.实验组细胞表面MUC2阳性染色明显减少,分布不均.对照组MUC2表达平稳且水平较高,其他3组均下降,LPS组降低最为明显,低谷在注射后6 h(0.1841±0.0047),明显低于对照组(0.2091±0.0060)(P＜0.01),预防组及治疗组变化趋势同LPS组,各时点MUC2均较LPS组高,方差分析提示组内及组间比较差异有统计学意义(P＜0.05).结论 PAF在内毒素血症肠道黏液屏障功能损伤中可能起一定作用,预防和治疗性应用PAF受体拮抗剂BN52021可减轻肠损伤.     

Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis

Because previous investigations have suggested that platelet activating factor and tumor necrosis factor-alpha (TNF-alpha) are important mediators of experimental necrotizing enterocolitis in the rat, we measured platelet activating factor, acetylhydrolase (the platelet activating factor breakdown enzyme), and TNF-alpha in the plasma of 12 human neonates with necrotizing enterocolitis and eight age-matched control subjects with similar gestational ages, postnatal ages, and weights. Almost all patients with necrotizing enterocolitis had elevated plasma platelet activating factor values (18.1 +/- 3.6 ng/ml vs. 3.1 +/- 0.9 ng/ml in control subjects, p less than 0.01). Plasma acetylhydrolase activity was lower in patients than in control subjects (10.6 +/- 0.7 nmol/ml/min vs 23.0 +/- 1.4 nmol/ml/min, p less than 0.01). Plasma TNF-alpha concentration was significantly elevated in patients with necrotizing enterocolitis (136 +/- 75 U/ml vs 1.5 +/- 0.8 U/ml, p less than 0.05), although the individual variation was high. There was no correlation between individual TNF-alpha and platelet activating factor levels. We conclude that platelet activating factor and TNF-alpha are elevated in patients with necrotizing enterocolitis and that suppressed platelet activating factor degradation contributes to the increased platelet activating factor levels; platelet activating factor and TNF-alpha may contribute to the pathophysiology of necrotizing enterocolitis.     

Renal diseases and platelet activating factor

The platelet-activating factor (PAF) is a molecule produced by several types of cells (monocytes, platelets, polynuclears, eosinophils and endothelial cells) and by different organs (lungs, heart, kidney). Its action concerns many inflammatory phenomena such as allergy, cerebral, cardiac or renal ischemia. The discovery of specific antagonists helped us to understand the pathophysiological effects of PAF in man. As PAF is involved in the mechanism of proteinuria and many other nephropathies, the use of antagonists for the treatment of such disorders seems valuable.     

新生儿缺氧缺血性脑病与血钙、血小板及血小板活化因子关系探讨

新生儿缺氧缺血性脑病(hypoxic_ischemic en-cephalopathy,HIE)是宫内窘迫、新生儿窒息等原因所致的脑部缺氧缺血性病变,是围产期新生儿脑损伤最常见的原因,发病机制极其复杂。研究表明新生儿HIE常伴有电解质紊乱,并存在不同程度的凝血机制异常,有可能发生DIC。随着分子生物学研究的深入,发现许多细胞因子与HIE的发病有关。为此我们对新生儿HIE与血清钙、血小板数及血小板活化因子(platelet activating factor,PAF)的关系进行了观察,并与同期产科出生正常新生儿进行x表2HIE中早产儿与足月儿血钙、血小板比较(±s)组别n血钙(mmol/L)…     

新生儿缺氧缺血性脑病血浆及脑脊液血小板活化因子的变化

目的　观察新生儿缺氧缺血性脑病 (HIE)血浆及脑脊液 (CSF)血小板活化因子 (PAF)的变化 ,探讨PAF在HIE发病中的作用。方法　于急性期和恢复期分别采集患儿血浆和CSF ,采用生物活性法检测血浆及CSF中PAF水平 ,并分析其与脑损伤和 1minApgar评分的关系。 结果　 1.HIE患儿急性期CSF中PAF水平明显高于对照组患儿 (P <0 .0 1) ,且与病情轻重呈明显正相关 (r =0 .6 5　P <0 .0 1) ;急性期中度与重度HIE患儿血浆PAF水平显著高于对照组 (P <0 .0 1) ,且与病情轻重呈明显正相关 (r =0 .5 9　P <0 .0 1) ,而轻度患儿与对照组无明显差异 (P >0 .0 5 ) ;恢复期与对照组比较无显著差异。 2 .血浆PAF水平与CSF中PAF水平呈正相关 ,血浆及CSF中PAF水平与脑损伤程度及 1minApgar评分呈明显正相关。 结论　PAF可能参与新生儿HIE的发病机制 ,CSF中PAF水平可作为判断HIE病情轻重和预后的重要指标     

血小板活化因子在新生儿缺氧缺血性脑病中的变化及意义

为探讨血小板活化因子（PAF）与新生儿缺氧缺血性脑病（HIE）之间的关系，应用改良的Henson法测定30例HIE患儿和20例正常新生儿血清PAF。结果表明，30例HIE患儿血清PAF明显增高，与正常对照组比较差异有显著性（P＜0．001）。提示：PAF与HIE有密切的相关性，PAF可作为判断HIE病情轻重程度和预后的重要指标。     

新生儿缺氧缺血性脑损伤与血小板活化因子的关系

目的　探讨新生儿缺氧缺血性脑损伤 (HIBD)时血浆血小板活化因子 (PAF)水平的变化。方法　建立血浆PAF的生物学测定方法 ,检测 75例缺氧缺血性脑病 (HIE)新生儿发病首日及病后 10d(恢复期 )血浆PAF水平 ,并与 3 0例健康新生儿PAF水平进行对比。结果　不同临床分度HIE患儿血浆PAF水平与对照组PAF均有显著性差异。中、重度HIE患儿发病首日血浆PAF水平明显高于病后 10d及正常对照组 (t =9.51,10 .14　P均 <0 .0 1)。结论　PAF参与新生儿HIBD的全过程     

Effect of dexamethasone on rat plasma platelet activating factor acetylhydrolase during the perinatal period

It has been previously reported that the administration of dexamethasone (DEX) to adult rats increases the activity of plasma platelet-activating factor acetylhydrolase (PAF-AH) and prevents the development of intestinal necrosis caused by platelet activating factor (PAF) injection. In this report, we examined the effect of DEX administration on plasma PAF-AH activity during the perinatal period. Timed-pregnant rats received DEX (0.2–1.0 mg/kg/d) or normal saline (controls) on days 16–18 (early group) or days 18–20 (late group) of gestation. Maternal plasma PAF-AH activity was lower in late gestation than in postpartum period (P < 0.001). Fetal and neonatal plasma PAF-AH activity was higher than maternal values (P < 0.05). No changes of PAF-AH activity were seen in maternal, fetal or neonatal plasma after prenatal DEX administration at the aforementioned doses. A higher dose of DEX (1.3 mg/kg/d × 4d) or cortisone (200 mg/kg/d) produced an elevation of maternal plasma PAF-AH activity (DEX 79.2 ± 3.0, cortisone 70.5 ± 1.9 vs. controls 49.4 ± 2.3 nmol/min/ml, P < 0.01), but resulted in a high fetal mortality. Treatment of newborn rats with DEX (0.5 mg/kg/d) on days 1–3 after birth, increased plasma PAF-AH activity on day 4 (DEX 292 ± 5 versus controls 140 ± 9 nmol/min/ml, P < 0.001) and day 6 (DEX 302 ± 12 versus controls 136 ± 6 nmol/min/ml, P < 0.001). Postnatal administration of DEX increases the plasma PAF-AH activity in the rat. Only high doses of prenatal corticosteroids that cause fetal death can elevate maternal plasma PAF-AH activity.     

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema

To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9–200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0–30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0–14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0–1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. Conclusion Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema. Received: 20 July 1998 / Accepted: 14 February 1999     

Plasma and urinary platelet activating factor concentrations and leukotriene releasing activity of leukocytes in steroid sensitive nephrotic syndrome of childhood

Platelet activating factor (PAF) is synthesized and secreted by glomerular mesangial and endothelial cells. It increases glomerular basement membrane permeability and induces proteinuria. Leukotrienes (LT) are mediators released by either leukocytes or glomerular cells under the PAF effect. The possible role of PAF in steroid sensitive nephrotic syndrome (SSNS) of childhood was studied in 8 children with SSNS in the acute stage, 5 children in remission and 8 healthy controls. The PAF concentrations in urine and plasma were determined. Leukocytes were stimulated in vitro and the LT release in response to stimulation was determined. The urinary and plasma concentrations of PAF were significantly higher in the acute phase than in remission and in control patients. Children with SSNS were found to have peripheral leukocytes with increased LT releasing activity in vitro. These results are in accordance with clinical and experimental observations indicating that PAF originates in the kidney and plays a role in normal kidney physiology. Urinary PAF concentrations may be related to proteinuria because they were strongly correlated in the present study. Elevated plasma PAF concentrations in the acute stage of SSNS could result from either its secretion from the circulating leukocytes or decreased acetyl hidrolase activity needed for its hydrolysis in plasma. The increased LT release in vitro suggests that these cells might have been activated by PAF secreted from glomeruli. It is proposed that PAF and different LT in systemic and glomerular circulation are important mediators in childhood SSNS.     

肠三叶因子在内毒素致幼鼠肠损伤中的作用及意义

目的：探讨内毒素(LPS)致幼鼠肠损伤中二胺氧化酶(DAO)及肿瘤坏死因子(TNF-α)的变化及基因重组肠三叶因子(rITF)的保护作用,为临床治疗提供实验依据。方法：Wistar幼鼠10日龄96只分为3组,A组:生理盐水对照组;B组:LPS组;C组:LPS+rITF组,每组32只。以生理盐水(1mL/kg),EcoliO55:B5(1mL/kg)、rITF(0.1mL/只、配制浓度5g/L)腹腔注射后2,6,24,72h断头处死动物,取动静脉混合血,测血DAO活性。留取肠组织,免疫组化法检测TNF-α蛋白含量,PCR法检测TNF-αmRNA表达。同时作电镜观测肠组织超微结构变化。结果：B组血浆DAO活性自LPS作用后2h即开始升高,至6h达到最高值,较A组差异有显著性(1.519±0.13U/Lvs1.081±0.04U/L,P<0.01),72h仍持续高值;C组血浆DAO活性较B组明显下降(P<0.01或P<0.05);与A组6h比较差异有显著性(P<0.01),其余各时间点差异无显著性(P>0.05);B组TNF-α积分光密度含量明显高于A组,以LPS作用后6h达高峰(37247.64±3387.59vs6191.02±482.32,P<0.01),C组TNF-α含量较B组明显降低,但仍高于A组(P<0.01);TNF-αmRNA在A组各时间点有微弱的表达,在B组各时间点表达明显增强,较A组差异显著(P<0.01);而C组各时间点表达明显减少,较B组差异显著(P<0.01或P<0.05)。电镜下肠组织超微结构:A组正常,B组变化明显,C组变化较B组减轻。结论：ITF可降低血浆DAO活性,抑制肠组织TNF-αmRNA及蛋白表达,减轻LPS所致幼鼠肠损伤,发挥保护作用。     

Increased neonatal platelet deposition on subendothelium under flow conditions: the role of plasma von Willebrand factor

In vitro platelet function of umbilical cord blood and neonatal peripheral vein blood from full-term newborns was compared with that of adults. Citrated whole blood was subjected to shear stress (1300 s(-1)) on subendothelial extracellular matrix (ECM)-coated wells in a cone and plate(let) analyzer. Adhered platelets on the ECM were quantitated by image analyzer. Both umbilical cord and neonatal peripheral blood platelets demonstrated more extensive adhesion than adult platelets, and similar aggregate formation on ECM. The ability of neonatal platelets to form aggregates on ECM was confirmed by scanning electron microscopy. Similar activation of neonatal and adult platelets after subjection to shear stress, in the suspension phase, was established by flow cytometry, which showed an increase in fibrinogen binding and a decrease in glycoprotein Ib expression on platelet membrane. The difference in adhesion rates between neonatal and adult platelets was preserved even when the hematocrit level of the neonatal blood was adjusted to that of adults. Reconstitution of neonatal or adult platelet-rich plasma with autologous or heterologous red packed cells yielded no change in adhesion and aggregation. When von Willebrand factor-covered plates were used to prevent deposition of plasma von Willebrand factor on the surface, no difference in platelet adhesion was seen between neonatal and adult blood. In conventional aggregometry assay, the response to ristocetin of washed platelets of either neonatal or adult source was higher on addition of plasma from neonates than from adults. Our data suggest that the extensive neonatal platelet deposition on ECM is mediated by plasma von Willebrand factor, which is known to be more multimerized and, therefore, more active in neonates than in adults. This mechanism may provide balanced primary hemostasis in neonates despite the platelet hyporeactivity to agonists without application of shear stress.     

Heterotaxia syndrome: the role of screening for intestinal rotation abnormalities.

BACKGROUND: Heterotaxia syndrome involves multiple anomalies, including cardiac malformations and intestinal rotation abnormalities. Most authors recommend routine radiological evaluation, with laparotomy and Ladd procedure if a rotation abnormality is found. AIMS: To determine if routine radiological screening is necessary, and if there is a group of children that can safely be managed expectantly. METHODS: Retrospective chart review of all children with heterotaxia syndrome from 1968 to 2002. RESULTS: Complete data were available for 177 patients. Twenty five (14%) had neonatal gastrointestinal symptoms (feeding intolerance, vomiting). Eleven of these had gastrointestinal contrast studies, of which seven were abnormal and led to surgery. Of the 152 asymptomatic neonates, nine had radiological screening and six of these were abnormal. Only one was thought to have a narrow based mesentery, but did not undergo surgery due to cardiac disease. There were no intestinal complications on follow up in this group. The other 143 asymptomatic children did not undergo radiological screening and were closely followed. Four subsequently developed gastrointestinal symptoms and had contrast studies; only one of these had malrotation and underwent a Ladd procedure. Of the remaining 139 patients who remained asymptomatic, 60 (43%) died of cardiac disease and none developed intestinal symptoms or complications related to malrotation on follow up. CONCLUSION: Asymptomatic children with heterotaxia syndrome have a low risk of adverse outcome related to intestinal rotation abnormalities. Routine screening may not be necessary as long as close follow up is done, and prompt investigation is performed for those that develop gastrointestinal symptomatology.     

The role of intestinal bifidobacteria on immune system development in young rats

Aim

The effects of intestinal bifidobacteria on the development of immunity in early life were explored.

Methods

Neonatal SD rats born and housed under strict barrier systems were fed from birth with sufficient antibiotics (bifidobacteria minimisation group) or supplemented daily with 1 × 10¹⁰ colony-forming units of live Bifidobacterium longum (bifidobacteria supplementation group). Relevant indices of immune development were determined at one, three and six weeks old.

Results

Compared to the control group, minimisation of the intestinal bifidobacteria delayed maturation of dendritic cells in Peyer's Patches and the development of T cells in the thymus, increased IL-4 secretion in the plasma, down-regulated IL-12, IL-10 mRNA and the interferon-γ/IL-4 mRNA ratio in intestinal mucosa, decreased interferon-γ mRNA in cultured peripheral blood mononuclear cells (PBMCs), and reduced immunoglobulin-M production in cultured PBMCs. Conversely, supplementation with bifidobacteria promoted dendritic cell maturation in Peyer's Patches, up-regulated IL-12, IL-10, interferon-γ mRNA and the interferon-γ/IL-4 ratio in intestinal mucosa, increased interferon-γ gene expression in cultured PBMCs, and raised immunoglobulin-M secretion in cultured PBMCs.

Conclusions

Intestinal bifidobacteria could promote the maturation of dendritic cells and its expression of IL-12 locally in the gut, influence the development of T cells in the thymus, favour the development of T-helper cell type 1 response by increasing the local and systemic expression of interferon-γ and ensure the intestinal regulatory T cell response by promoting the local expression of IL-10. In addition, they enhance antibody synthesis by PBMCs, thereby affecting the development of both the gut and systemic immunity in early life.     

脑源性神经营养因子对缺氧胚脑皮质神经元的保护作用

目的 通过胚鼠皮质神经元的体外培养，观察遭受缺氧刺激时，脑源性神经营养因子（BDNF）对神经元的保护作用。方法 用台盼蓝染色法动态观察培养神经元的存活率及加入BDNF对生理培养状态的皮质神经元的作用。同时用四氮唑盐（MTT）比色法观察不同缺氧时间实验组及对照组神经元活性的差异。结果 BDNF对正常皮质神经元有维持存活效应；对缺氧神经元有确切保护作用。该保护作用有时间依赖性，缺氧前24h加入BDNF对缺氧神经元的保护效果较缺氧即刻加入为好。结论 体外实验证实BDNF可维持皮质神经元存活，并可减轻皮质神经元所遭受的缺氧损害。     

Role of nitric oxide in hypoxia-induced changes in newborn rats

In order to investigate the role of nitric oxide (NO) in hypoxic tissue damage in newborns, we studied the effects of systemic administration of an inhibitor of NO synthase, N(G)-nitro-L-arginine (L-NNA), and the precursor for the synthesis of NO, L-arginine (L-ARG), on the biochemical and histological changes in brain, heart, lung, liver, kidney, intestine, and skeletal muscle tissues. Four groups of 1-day-old Wistar rat pups were used: control, hypoxic, L-ARG, and L-NNA groups. L-ARG 100 mg/kg or L-NNA 2 mg/kg was administered as a bolus intraperitoneally 1.5 h before hypoxia. Hypoxia increased lipid peroxidation in all tissues except muscle; this increase was prevented by L-NNA and L-ARG in brain, heart, lung, kidney, and liver tissues. L-NNA in intestine and L-ARG in muscle tissue increased lipid peroxidation. The tissue-associated myeloperoxidase activity was decreased in the liver by L-NNA and L-ARG. Histopathological changes in intestines were villous epithelial separation and hyperemia in hypoxic and L-NNA groups which were not observed in control and L-ARG groups. In lungs, pulmonary hemorrhage was observed only in the hypoxic group. These data suggest that NO acts both as a destructive and a protective agent in the pathogenesis of hypoxia-reoxygenation injuries.     

肠三叶因子对内毒素血症幼鼠肠组织Toll样受体2和4表达的影响

目的：探讨肠三叶因子对内毒素血症幼鼠肠组织Toll样受体（TLR）2、4表达的调节及对肠组织损伤的影响。方法：24只10日龄Wistar幼鼠随机分为正常对照组（NS组,n=8,生理盐水1 mL/kg腹腔注射）;内毒素血症组（LPS组,n=8,LPS 5 mg/kg 腹腔注射）;肠三叶因子组（ITF组,n=8,重组肠三叶因子 0.1 mL/只＋LPS 5 mg/kg腹腔注射）。于腹腔注射后3 h处死,留取远端回肠组织观察肠组织病理改变,RT-PCR检测肠组织TLR2、4-mRNA的表达。结果：光镜下NS组肠组织结构正常,ITF组和LPS组均可见间质和上皮细胞水肿,ITF组较LPS组病变明显减轻。ITF组肠组织TLR2 mRNA 表达较NS组、LPS组明显增高（P＜0.01）; 而TLR4 mRNA表达较NS组和LPS组明显下降（P＜0.01）。结论：肠三叶因子可减轻内毒素血症幼鼠肠组织损伤,这种保护作用可能与其下调TLR4 mRNA的表达相关。     

维甲酸、血小板衍生生长因子对早产新生大鼠高浓度氧肺损伤的影响

目的观察维甲酸（RA）和血小板衍生生长因子（PDGF）对高浓度氧（简称高氧）抑制早产新生大鼠肺发育的影响，探讨其作用机制。方法1日龄早产SD大鼠随机分为：空气＋生理盐水组（Ⅰ组）、高氧＋生理盐水组（Ⅱ组）、空气＋RA组（Ⅲ组）、高氧＋RA组（Ⅳ组）。Ⅱ、Ⅳ组持续暴露于85％氧气中。Ⅲ、Ⅳ组每目腹腔注射RA500μg／kg，Ⅰ、Ⅱ组注射相同剂量的生理盐水。应用RT—PCR和免疫组织化学法检测各时间点（生后4、7、10、14及21d）各组大鼠肺组织PDGFmRNA和蛋白表达水平。结果随日龄的增加，PDGF—A、-B mRNA及蛋白表达发生不同的变化。与Ⅰ组比较，高氧暴露下PDGF-B mRNA和蛋白表达显著增高（P〈0．05），但PDGF-A mRNA及蛋白表达却显著降低（P〈0．05）。RA上调PDGF—A mRNA及蛋白表达（P〈0．05），但对PDGF—B mRNA及蛋白表达作用不显著（P〉0．05）。结论高氧暴露下，PDGF—AmRNA及蛋白表达受抑，PDGF—BmRNA及蛋白表达增强。PDGF-A、-B共同参与了高氧暴露下肺组织损伤过程。RA上调PDGF—AmRNA及蛋白表达，能部分逆转高氧引起的肺损伤。     

法舒地尔对大鼠低氧性肺动脉高压及其肺血管结构重建的影响

目的 探讨Rho激酶抑制剂法舒地尔对大鼠低氧性肺动脉高压(HPH)及其肺血管结构重建的影响.方法 采用常压间断低氧法建立大鼠HPH模型.雄性SD大鼠24只,随机均分为对照组、模型组和法舒地尔干预组.测各组大鼠平均肺动脉压力(mPAP)、平均颈动脉压力(mCAP)、右心室肥厚指数(RVHI);光镜下结合图像分析进行肺血管结构重建观察;透射电镜观察肺小动脉内皮细胞超微结构的变化.结果 ①模型组mPAP、RVHI、肺小动脉管壁厚度与外径比值(WT%)、管壁面积与管总面积比值(WA%)分别为(31.38±1.98)mmHg、0.47±0.03、(31.13±5.74)%、(54.93±3.34)%均明显高于对照组(15.25±0.91)mmHg、0.25±0.02、(13.24±2.03)%、(31.81±3.62)%,P均＜0.01;管腔面积与管总面积比值(LA%)为(45.07±3.34)%,明显低于对照组(68.20±3.62)%,P＜0.01;透射电镜显示模型组肺小动脉内皮细胞损伤明显,内皮细胞周围平滑肌细胞增生、肿胀,胶原纤维增生.②法舒地尔干预组mPAP、RVHI、WT%、WA%分别为(16.63±1.53)mmHg、0.27±0.02、(17.08±2.24)%、(37.30±3.69)%显著低于模型组(P＜0.01),LA%为(62.70±3.69)%明显高于模型组(P＜0.01).法舒地尔干预后肺小动脉内皮细胞损伤、平滑肌细胞及胶原纤维增生均明显减轻.③各组间mCAP差异无统计学意义(F=1.239,P＞0.05).结论 法舒地尔对低氧所致的肺动脉高压、右心室肥厚及肺血管结构重建具有较好的预防和逆转作用.