卡维地洛、福辛普利及其合用对急性心肌梗死大鼠左室重塑的影响

本研究通过卡维地洛、福辛普利单剂治疗与联合应用对大鼠急性心肌梗死 (AMI)左室重塑作用的比较探讨二者联合应用对防治AMI左室重塑的影响。1 材料与方法 :取体重 ( 2 2 0± 2 0 )g的Wistar雄性大鼠(第三军医大学动物中心提供 ) ,采用Pfeffer等的手术方法 ,在乙醚麻醉下 ,结扎冠状动脉左前降支 ,同时设立假手术组。术后 2 4h将存活大鼠随机分为 :⑴AMI对照组 (n =10 ) ;⑵卡维地洛组 ( 1mg·kg- 1 ·d- 1 ,n =10 ) ;⑶福辛普利组 ( 10mg·kg- 1 ·d- 1 ,n =10 ) ;⑷二药合用组 (卡维地洛 1mg·kg- 1 ·d- 1 ,福辛普利 10mg·kg- 1 ·d-…     

非清髓性异基因造血干细胞移植后淋巴细胞重建

我们观察了 7例白血病患者行非清髓性异基因造血干细胞移植 (NAST)后淋巴细胞功能的变化报告如下。一、资料和方法1.对象 :7例均为我院 2 0 0 0年 12月～ 2 0 0 1年 10月行NAST的白血病患者 ,女 4例 ,男 3例 ,年龄 17～ 5 6岁。患者的资料 ,见表 1。 10例健康作为对照组。预处理方案 :氟拉达滨 30mg·m-2 ·d-1,移植前第 9～ 5天或环磷酰胺 30mg·kg-1·d-1,移植前 4～ 3天 ;马利兰 2mg·kg-1·d-1,移植前 8～ 5天 ;抗胸腺球蛋白 10mg·kg-1·d-1,移植前第 7～ 4天。环孢素A(CsA) 2mg·kg-1·d-1,移植前 1天开始用 ,胃肠功能恢复后改为…     

氯沙坦、依那普利及其合用对腹主动脉缩窄型高血压大鼠的影响

目的　探讨依那普利、氯沙坦及其合用对腹主动脉缩窄型高血压大鼠血压、心肌肥厚程度和心肌组织丝裂原活化蛋白激酶 (MAPK)的活性及表达的影响。方法　采用腹主动脉缩窄型高血压大鼠模型 ,然后将动物随机分为 7组 (n均 =6 )。分别为氯沙坦 (10 mg· kg- 1 · d- 1 )组 ,氯沙坦 (30 mg· kg- 1 · d- 1 )组 ,依那普利 (4mg· kg- 1 · d- 1 )组 ,依那普利 (12 mg· kg- 1· d- 1 )组 ,依那普利合用氯沙坦 (4m g· kg- 1· d- 1和 10 m g· kg- 1· d- 1 )组和安慰剂组。以假手术组作对照。给药 5周后测定左心室重量与体重比值、平滑肌肌动蛋白表达和 MAPK蛋白表达变化。结果　与假手术组比较 ,大鼠腹主动脉缩窄术后 6周血压明显升高 ,心肌组织发生明显肥厚 ,平滑肌肌动蛋白和 MAPK蛋白表达增高 (P<0 .0 1)。与安慰剂组比较 ,氯沙坦、依那普利及其合用可降低平均动脉血压 ,减轻心肌肥厚 ,同时降低平滑肌肌动蛋白和 MAPK蛋白表达 (P<0 .0 1) ,且氯沙坦、依那普利的作用呈剂量依赖性。与单用氯沙坦或依那普利比较 ,氯沙坦和依那普利合用可进一步降低平均动脉血压、减轻心肌肥厚和 MAPK蛋白表达 (P <0 .0 5 )。结论　 MAPK是介导高血压心肌肥厚的重要信号分子。氯沙坦、依那普利均能减轻心肌肥厚和 MAPK蛋白?     

SU5416抑制胃癌生长和肝转移的实验研究

目的　研究血管内皮细胞生长因子抑制物SU5 4 16对裸鼠原位种植人胃癌生长和肝转移抑制作用 ,探讨其对癌细胞凋亡的影响。方法　建立人胃癌裸鼠原位种植转移模型 ,随机分为 4组。种植后第 1周开始 ,分别自腹腔注射生理盐水 (对照组 )、5 氟尿嘧啶 (30mg·kg-1·d-1,5 FU组 )、SU5 4 16(15mg·kg-1·d-1,SU5 4 16组 )、5 FU与SU5 4 16联合应用 (5 FU 30mg·kg-1·d-1,SU5 4 16 15mg·kg-1·d-1,5 FU +SU5 4 16组 ) ,每天 1次 ,共 7周。第 8周处死动物 ,测量原位肿瘤瘤重、抑瘤率、微血管密度(MVD)、胃癌细胞凋亡指数 (AI) ,观察肿瘤细胞肝转移情况。结果　对照组、5 FU组、SU5 4 16组、5 FU+SU5 4 16组的原位肿瘤瘤重分别为 (1.35± 0 .4 2 )、(0 .75± 0 .33)、(0 .34± 0 .14 )及 (0 .2 1± 0 .15 ) g ;抑瘤率分别为 4 4 .5 % ,79.3% ,84 .4 % ;肝转移率分别为 90 .0 % ,36 .4 % ,2 5 .0 % ,0 %。MVD分别为 14 .6± 5 .8,13.1± 4 .7,3.9± 1.8,2 .1± 1.5 ;AI分别为 (3.76± 2 .2 5 ) % ,(6 .81± 4 .92 ) % ,(9.82± 3.76 ) % ,(17.6 5± 9.85 ) %。与对照组、5 FU组相比 ,SU5 4 16组、5 FU +SU5 4 16组胃癌生长、肝转移及MVD受到明显抑制 (P <0 .0 5 ) ,AI明显增高 (P <0 .0 5 )。结论　SU     

不同剂量阿司匹林对兔动脉粥样硬化斑块进展的抑制作用

目的　利用高胆固醇饮食 (2 % )并免疫损伤诱发的动脉粥样硬化斑块模型 ,评价不同剂量阿司匹林 (aspirin)对动脉粥样硬化斑块的抑制作用。方法　将 40只建立动脉粥样硬化斑块模型的新西兰大白兔随机分为阿司匹林小剂量 (4mg·kg- 1·d- 1)、中剂量 (12mg·kg- 1·d- 1)、大剂量 (2 0mg·kg- 1·d- 1)和高胆固醇四组 ,另设正常对照组 ,每组各 10只。测定指标包括 0、2、12周时的血脂和 12周时的血清C反应蛋白 (CRP)和单核细胞趋化因子 1(MCP 1)以及主动脉斑块 /内膜面积比、内 /中膜厚度比和斑块脂质含量。结果　阿司匹林小、中、大剂量组与高胆固醇组相比 ,斑块 /内膜面积比分别减少 2 0 9%、43 9%和 42 8% ,内 /中膜厚度比分别减少 49 0 %、67 1%和 69 0 % ,斑块脂质含量分别减少 2 8 8%、3 5 0 %和 48 6% (P <0 0 5～ 0 0 1) ;CRP和MCP 1也显著降低 (P均 <0 0 1)。三个治疗组间比较 ,各指标在大剂量组显著低于小剂量组 (P <0 0 5～ 0 0 1) ,但大、中剂量组间差异无显著性 (P >0 0 5)。结论　阿司匹林呈剂量相关地通过抗炎作用抑制动脉粥样硬化斑块的进展 ,效应以中剂量 (12mg·kg- 1·d- 1)为佳     

依那普利氯沙坦及两者合用对心肌梗死后大鼠左室重塑干预的对比研究

目的 :对比依那普利、氯沙坦及两者合用对急性心肌梗死 (AMI)后大鼠左室重塑 (LVRM)的防治作用。方法 :AMI术后 2 4h存活的 4 3只雄性Wistar大鼠随机分为 :①AMI对照组 ,②依那普利 (10mg·kg- 1 ·d- 1 )组 ,③氯沙坦 (2 0mg·kg- 1 ·d- 1 )组 ,④依那普利 (5mg·kg- 1 ·d- 1 )与氯沙坦 (10mg·kg- 1 ·d- 1 )合用组 ;另设假手术组及正常对照组。各治疗组于术后第 2日起灌胃给药 ,连续 4周。行心脏标本病理分析 ,放免法测血浆和左室非梗死区 (LVNIZ)血管紧张素Ⅱ (AngⅡ )含量 ,氯氨T法测LVNIZ羟脯氨酸含量 (HC)。结果 :AMI后心脏重量 (HW)、心脏重量指数 (HWI)、左室重量 (LVW )、左室重量指数 (LVWI)、LVNIZAngⅡ、HC均显著增加 (P <0 .0 5～ 0 .0 1) ;与AMI对照组相比 ,各治疗组上述参数均降低 (P <0 .0 5～ 0 .0 1) ,其中合用药组降低HWI、LVWI最为显著 (均P <0 .0 1) ,而依那普利组HC降低最为明显 (P <0 .0 1)。AMI后血浆AngⅡ明显升高 ,与AMI对照组相比 ,依那普利及合用药组均使其显著降低 ,而氯沙坦组使其更加升高。结论 :依那普利、氯沙坦及两者合用均能有效改善大鼠心肌梗死后LVRM ,合用药对降低HWI、LVWI有叠加效应。     

超声评价贝那普利与氯沙坦联合应用对自发性高血压大鼠心功能的影响

目的超声评价贝那普利或氯沙坦单用与合用对自发性高血压大鼠(SHR)心脏结构及功能的影响。方法选用55周龄WKY12只,同龄SHR48只,随机分为SHR对照组,贝那普利组(10mg·kg-1·d-1),氯沙坦组(30mg·kg-1·d-1),贝那普利(10mg·kg-1·d-1)+氯沙坦(15mg·kg-1·d-1)组。监测动脉收缩压及体重、心率等基础指标;超声心动图进行左室腔径各指标测量及二尖瓣血流频谱分析;比较各组大鼠的左心室质量指数(LVMI);光镜观察心肌组织结构改变。结果各药物干预组SHR的收缩压低于SHR对照组(P<0.01);各用药组能不同程度降低LVPW、IVS和升高LVEDD值(P<0.01),且能不同程度升高LVEF、E/A值(P<0.01),均以药物合用组更为显著(P<0.01);另外,各用药组均能改善心肌细胞的排列、肥大、凋亡及坏死,改善程度:药物合用组>氯沙坦组>贝那普利组。结论贝那普利和氯沙坦联合治疗SHR对其心脏结构和功能的改善作用优于单用。     

普通型间质性肺炎和非特异性间质性肺炎肺组织中不同细胞因子的表达及其意义

目的　研究转化生长因子 (TGF) β1、碱性成纤维细胞生长因子 (b FGF)、白细胞介素 8(IL 8)、白细胞介素 13(IL 13)、γ干扰素 (IFN γ)在普通型间质性肺炎 (UIP)和非特异性间质性肺炎(NSIP)肺组织中的分布、表达及意义。方法　经胸腔镜或开胸肺活检获取 5例UIP和 8例NSIP患者的肺组织。对照组 5例 ,来自手术切除的远离肺癌原发灶的周边肺组织。用免疫组化法半定量分析细胞因子的分布及表达。结果　TGF β1、IL 8、b FGF主要分布在肺泡上皮细胞、肺泡巨噬细胞、细支气管上皮细胞 ,UIP组表达强于NSIP组和对照组。IL 13主要分布在肺泡上皮细胞、肺泡巨噬细胞、间质单个核细胞 ,UIP、NSIP组表达无明显差异 ,但均强于对照组。IFN γ主要分布在间质单个核细胞 ,NSIP组表达强于UIP组和对照组。UIP组的IL 13/IFN γ比值为 (2 18± 0 76 ) ,NSIP组为(0 95± 0 2 8) ,对照组为 (0 91± 0 16 ) ,3组比较差异均有显著性 (P值均 <0 0 5 ) ,而NSIP组与对照组比较差异无显著性。对照组只有肺泡巨噬细胞表达上述各细胞因子。结论　TGF β1、IL 8、b FGF在UIP和NSIP患者肺组织中表达强度的不同和IL 13/IFN γ的是否平衡可能参与了UIP和NSIP不同的发病过程。     

泼尼松联合甲氨蝶呤氯喹治疗系统性红斑狼疮的研究

目的　回顾性研究 ,旨在探讨PMC治疗 (小剂量泼尼松合并甲氨蝶呤、氯喹 )对于轻、中度活动期SLE患者的疗效及副作用 ,以减少药物用量和副作用。方法　将入选的门诊患者按起始激素剂量 ,分为A (泼尼松剂量≤ 0 2mg·kg-1·d-1)和B (泼尼松 0 5～ 0 6mg·kg-1·d-1)两组 ,并联合应用甲氨蝶呤 7 5～ 10mg/周及氯喹 0 2 5g/d ,各 30例。观察疗效和副作用 ,为期 1年。结果　A组积分由治疗前的 2 1± 1 4降至 0 9± 0 7,B组感染多于A组 (2 2∶7,P <0 0 0 1) ,其中多为肺部感染 ,其次为皮肤感染。B组由 2 9± 2 3降至 1 3± 1 3。二组治疗前后相比疗效显著 ,但A、B两组间的疗效差异无显著性。B组中出现了库兴综合征及股骨头无菌性坏死 ,A组没有。结论　PMC方案对没有严重内脏累及的轻到中度的SLE患者有效。但在加大激素剂量的B组 ,感染问题比较突出     

Mizoribine protects against bleomycin-induced lung injury

Bleomycin (BLM)-induced lung injury has become a model for studies of interstitial pneumonitis and pulmonary fibrosis. BLM induces lung injury in two phases: early inflammation characterized by infiltration of inflammatory cells into the lungs, followed by a late phase of fibrosis characterized by deposition of collagen. In this study, we examined the role of mizoribine (MZB) in the regulation of inflammatory tissue injury caused by BLM. We examined the role of MZB using a mouse model of BLM-induced lung injury. We demonstrated that mice subjected to instillation of BLM into the lungs had a significantly increased number of macrophages and lymphocytes in bronchoalveolar lavage fluid (BALF), but that those treated with MZB in the early phase showed a significant reduction in the total number of BALF macrophages and lymphocytes. However, MZB was unable to inhibit fibrosis in the late phase of BLM injury. Our findings suggest that MZB inhibits the proliferation of both lymphocytes and macrophages in the early phase of the BLM-induced acute inflammatory response, as well as its development and amplification, but does not inhibit fibrotic change in the late phase.     

白三烯抑制剂对博莱霉素所致大鼠肺纤维化的干预作用

目的 观察白三烯抑制剂(LT-S)齐留通对博莱霉素(BLM)所致大鼠肺纤维化模型肺纤维化形成过程的影响.方法 54只SD雄性大鼠随机分为正常组(C组)、模型对照组(M组)和LT-S组(S组)3组,每组18只.S组于气管内滴注BLM(5 mg/kg)诱导肺纤维化,于造模当天开始每日给予齐留通100 mg/kg灌胃;M组以生理盐水代替齐留通灌胃;C组均用生理盐水代替BLM和齐留通.各组动物均于制模后的第7天、第14天和第28天分别随机处死6只动物,分取肺组织行病理切片苏木精-伊红染色和Masson染色观察肺泡炎和肺纤维化程度、碱水解法检测肺组织羟脯氨酸(Hyp)浓度、免疫组织化学技术检测肺组织α平滑肌肌动蛋白(α-SMA)和转化生长因子β1(TGF-β1)水平.结果 S组肺泡炎和肺纤维化程度及肺组织Hyp含量均显著低于M组,其TGF-β1和α-SMA在肺组织中的表达水平亦均显著低于M组.结论 LT-S可减轻BLM诱导的大鼠肺纤维化,并可能通过抑制TGF-β1蛋白表达而实现对成纤维原细胞增殖的抑制.     

Mizoribine protects against bleomycin-induced lung injury

Abstract

Bleomycin (BLM)-induced lung injury has become a model for studies of interstitial pneumonitis and pulmonary fibrosis. BLM induces lung injury in two phases: early inflammation characterized by infiltration of inflammatory cells into the lungs, followed by a late phase of fibrosis characterized by deposition of collagen. In this study, we examined the role of mizoribine (MZB) in the regulation of inflammatory tissue injury caused by BLM. We examined the role of MZB using a mouse model of BLM-induced lung injury. We demonstrated that mice subjected to instillation of BLM into the lungs had a significantly increased number of macrophages and lymphocytes in bronchoalveolar lavage fluid (BALF), but that those treated with MZB in the early phase showed a significant reduction in the total number of BALF macrophages and lymphocytes. However, MZB was unable to inhibit fibrosis in the late phase of BLM injury. Our findings suggest that MZB inhibits the proliferation of both lymphocytes and macrophages in the early phase of the BLM-induced acute inflammatory response, as well as its development and amplification, but does not inhibit fibrotic change in the late phase.     

Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced by bleomycin in mice

Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary fibrosis. We previously demonstrated that N-acetylcysteine (NAC), an antioxidant, inhibited adhesion molecule expression and cytokine production in lung cells. When NAC is inhaled into the alveolar space, it is expected to directly interact with inflammatory cells and to elevate glutathione levels in the epithelial lining fluids. We therefore examined whether inhaled NAC inhibits lung fibrosis induced by bleomycin (BLM). Male ICR mice were given a single intravenous injection of BLM (150 mg/ kg). Thirty milliliters of NAC (70 mg/ml) or saline were inhaled twice a day for 28 d using an ultrasonic nebulizer. In the inflammatory phase (Day 7), NAC administration attenuated the cellular infiltration in both bronchoalveolar lavage fluid (BALF) and alveolar tissues. At Day 28, the fibrotic changes estimated by Aschroft's criteria and hydroxyproline content in the NAC inhalation group were significantly decreased compared with the BLM-only group (p < 0.05). CXC chemokines, macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant (KC), and CC chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), in BALF were mostly elevated on Day 7 in the BLM-only group; however, these elevations were significantly repressed by NAC inhalation (p < 0.05). Lipid hydroperoxide (LPO) was also quantified in BALF. LPO was markedly increased on Day 3 in the BLM-only group, and this increase was significantly decreased by NAC inhalation (p < 0.05). These results revealed that aerosolized NAC ameliorated acute pulmonary inflammation induced by BLM injection via the repression of chemokines and LPO production, resulting in the attenuation of subsequent lung fibrosis. These findings are limited to the BLM-induced lung fibrosis animal model. However, NAC inhalation will be expected to be a potential therapy for patients with other interstitial pneumonias because ROS are involved in the pathogenesis of lung injury in most interstitial pneumonia.     

肺纤维化大鼠肺组织血小板源性生长因子和纤溶酶原激活物抑制剂1表达的研究

目的 观察肺纤维化大鼠肺组织中血小板源性生长因子(PDGF)和纤溶酶原激活物抑制剂1(PAI-1)表达的变化,探讨其在肺纤维化中的作用机制.方法 30只 Wistar大鼠随机分为博莱霉素组(BLM组)和对照组(NS组):①BLM组,气管内灌注BLM(5 mg/kg)诱导肺纤维化;②NS组,气管内灌注NS(剂量与用法同上).于气管内灌注后第7、14和28天各分别处死5只大鼠,取右肺支气管肺泡灌洗液(BALF),进行细胞分类、计数;留取左肺组织匀浆测定羟脯氨酸含量;采用免疫组织化学法测定PDGF和PAI-l蛋白的表达.结果 ①BLM组肺组织中胶原含量在第7天开始升高,第14、28天进行性增高,明显高于NS组(P＜0.01);②BLM组肺组织中PDGF蛋白表达在第7天达高峰,之后下降,第28天时仍高于NS组(P ＜0.05),与BALF中的细胞总数密切相关;③BLM组肺组织中PAI-1的表达在第7天开始升高,第28天达到高峰,与肺组织中胶原的含量密切相关(r=0.952,P＜0.01).结论 PDGF和PAI-1可能通过影响细胞外基质的代谢及胶原的沉积促进肺纤维化的发生.     

Pulmonary fibrosis and antioxidant agents

Lung inflammatory cells in idiopathic pulmonary fibrosis (IPF) is characterized by an increased spontaneous production of oxidants. This suggests that the oxidants may play a role in causing the epithelial cell injury in the early stage of IPF. Bleomycin (BLM) induces pulmonary fibrosis by oxidant production. We tested the hypothesis that a dietary supplement of vitamin E (VE) may protect against, and its deficiency may exacerbate, BLM-induced pulmonary fibrosis. Because the hamster is known to be the best model among animals studied mimicking human lung antioxidant enzyme activities, Syrian Golden hamsters were used in this study. In dietary VE supplement and BLM treated group (Ead.B), mean serum VE concentration increased by about 3 times that of control (C) and the BLM treated group (CB). Despite the remarkably high VE content, no significant difference was found between CB and Ead.B for pressure-volume (PV) curves and morphological data. In BLM treated with dietary VE deficient group (Ede.B), serum VE concentrations markedly decreased on all experimental days compared with other groups. Mechanical properties in P-V curves of Ede.B showed most less distensible characteristics in early stage and most distensible characteristics in later stage. These emphysematous changes observed in P-V curves in the later stage of Ede.B, coincided with the morphological observations. In the early stage of BLM treatment, lipid peroxide concentrations in the lung tissue were significantly higher in Ede.B compared with other groups. It was concluded that a dietary supplement of VE cannot protect against BLM-induced pulmonary fibrosis, and a dietary VE deficiency exacerbates BLM lung injury to produce on emphysema in the hamster.     

博莱霉素致肺纤维化大鼠肺组织表面活性物质表面ABCmRNA？…

目的 观察博莱霉素致肺纤维化大鼠肺组织表面活性物质蛋白（ＳＰ）Ａ，Ｂ，ＣｍＲＮＡ的表达。方法 气管内灌注博莱霉素Ａ５，复制肺纤维化模型，分别于３，７，１４和２８天处死动物，提取肺组织总ＲＮＡ，进行Ｎｏｒｔｈｅｒｎ杂交。结果 肺纤维化大鼠肺泡Ⅱ型上皮细胞数量增加，灌注博莱霉素后第３天ＳＰ－Ａ，ＳＰ－Ｂ及ＳＰ－ＣｍＲＮＡ的表达即开始下降，７天时降至最低点，而后于１４天时开始回升，至２８天时上升最明显。     

The influence of dexamethasone on the proliferation and apoptosis of pulmonary inflammatory cells in bleomycin-induced pulmonary fibrosis in rats

OBJECTIVE: The aim of this study was to investigate the inhibitory effect of dexamethasone on the state of proliferation/apoptosis of the pulmonary inflammatory cells in a rat pulmonary fibrosis model induced by bleomycin. METHODOLOGY: Seventy-five pathogen-free Sprague-Dawley (SD) rats were randomly divided into three groups: control, bleomycin (BLM) and dexamethasone (DXM) groups with 25 rats in each group. Each group was then divided into five subgroups based on time of study (1-, 3-, 7-, 14- and 28-days). BAL fluid was obtained, the cells were counted and a differential was performed. A lower DNA content in apoptotic cells was detected and quantitated by flow cytometry. Haematoxylin and eosin staining was performed to observe the extent of alveolitis and fibrosis of lung tissue; the morphological changes in apoptotic cells were discerned by transmission electron-microscopy and a semi-quantitative assessment of apoptotic cells in lung tissue was performed using in situ TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling). RESULTS: The total number of inflammatory cells and the percentage of neutrophils in BAL fluid in almost every subgroup of the DXM group were significantly lower than those in corresponding subgroups of the BLM group (P < 0.01). The percentages of apoptotic cells in BAL fluid in the 14-day and 28-day subgroups of the DXM group were higher than those in corresponding subgroups of the BLM group (P < 0.05). The peak of alveolitis in the DXM group shifted backward and the extent of fibrosis was less than that in the BLM group. The apoptosis index (AI) of inflammatory cells in each of the DXM subgroups was higher than that in corresponding BLM subgroups except for day 14. CONCLUSION: Dexamethasone can induce apoptosis of pulmonary inflammatory cells and reduce the extent of alveolitis and fibrosis in bleomycin-induced pulmonary fibrosis of rats.     

The research of pancadherin and beta-catenin expression in pulmonary tissue of mice with bleomycin-induced pulmonary fibrosis]

OBJECTIVE: To investigate the changes of pancadherin(Pan-cd) and beta-catenin(beta-cat) expression in pulmonary tissue of mice with bleomycin (BLM)-induced pulmonary injury and explore the relation between the Pan-cd/beta-cat expression and pulmonary fibrosis. METHOD: A single dose of BLM was intratracheally injected to induce pulmonary fibrosis of mice. Animals were killed and immunohistochemical methods were used with polyclonal anti-Pan-cd and anti-beta-cat antiserum. RESULTS: The expression of Pan-cd in type I alveolar cells was down-regulation. The expression of Pan-cd in type II alveolar cells was induced. The expression of Pan-cd and beta-cat in small airway epithelial cells were all down-regulation and were repeated with the way of down-regulation-reparation-down-regulation. The expression of Pan-cd on membrane in small airway epithelial cells decreased, whereas the cytoplasmic expression increased and was repeatedly alternated between cytoplasma with membrane. The expression of Pan-cd in alveolar macrophage and interstitial cells increased. CONCLUSION: The abnormal expression of cadherin and beta-cat may play a role in the pathogenesis of pulmonary fibrosis after pulmonary injury.     

转录活化子1反义寡核苷酸对肺纤维化大鼠肺组织中细胞因子和胶原表达的影响

目的 观察信号转导子与转录活化子1(STAT1)反义寡核苷酸雾化吸入对博来霉素致肺纤维化大鼠肺组织中Ⅰ、Ⅲ型胶原,纤溶酶原激活物抑制剂-1(PAI-1),转化生长因子-β_1(TGF-β_1)和羟脯氨酸表达的影响.方法 将45只Wistar大鼠按随机数字表法分为生理盐水组、博来霉素组和寡核苷酸组,每组15只,分别在气管内灌注并雾化吸入生理盐水、博来霉素、STAT1反义寡核苷酸.分别于雾化后第7天、第14天和第28天每组各处死5只大鼠.肺组织HE染色和Masson染色观察肺泡炎和肺纤维化改变,免疫组织化学SP法测定肺组织中TGF-β_1、PAI-1表达,逆转录PCR测定肺组织中Ⅰ、Ⅲ型胶原mRNA表达,肺组织匀浆测定羟脯氨酸含量.样本均数间比较采用单因素方差分析和q检验.结果 寡核苷酸组大鼠各时间点的肺泡炎和肺纤维化程度均较博来霉素组减轻.博来霉素组和寡核苷酸组大鼠肺组织中TGF-β、PAI-1表达水平均明显高于生理盐水组,博来霉素组和寡核苷酸组大鼠雾化后第7天TGF-β、PAI-1的积分吸光度值分别为182±12和169±12、128±11和113±13,明显高于生理盐水组的21±6和27±9,第28天时(68±7和87±7、54±8和57±8)仍高于生理盐水组(22±7和26±7);雾化后第7天、第14天和第28天,寡核苷酸组大鼠Ⅰ、Ⅲ型胶原mRNA表达水平分别为1.36±0.10、1.19±0.28、1.22±0.24和1.20±0.09、0.62±0.09、0.76±0.12,明显低于博来霉素组(3.29±0.28、2.04±0.25、1.91±0.30和1.63±0.15、1.58±0.13、1.12±0.09),寡核苷酸组大鼠肺组织中羟脯氨酸含量(mg/g)分别为3.02±0.13、3.24±0.31和3.60±0.16,明显低于博来霉素组的3.76±0.10、3.92±0.30和4.62±0.28.结论 STAT1反义寡核苷酸雾化吸入能减轻博来霉素致肺纤维化大鼠肺泡炎和肺纤维化,其机制可能与抑制TGF-β_1、PAI-1的表达,Ⅰ、Ⅲ型胶原mRNA表达减少,羟脯氨酸含量降低有关.