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

ＩＮＣＲＥＡＳＥＤＥＸＰＲＥＳＳＩＯＮＯＦＰＤＧＦＡＮＤＣ－ＭＹＣＧＥＮＥＳＩＮＬＵＮＧＳＡＮＤＰＵＬＭＯＮＡＲＹＡＲＴＥＲＩＥＳＯＦＰＵＬＭＯＮＡＲＹＨＹＰＥＲＴＥＮＳＩＶＥＲＡＴＳＩＮＤＵＣＥＤＢＹＨＹＰＯＸＩＡ￥ＣａｉＹｉｎｇｎｉａｎ；（蔡英年...     

Effects of IL-4 on cyclooxygenase-2 and platelet-derived growth factor in the lungs of COPD rats

Objective： To explore the role of interleukin 4（IL-4）, expressions of cyclooxygenase-2 （COX-2） and platelet-derived growth factor （PDGF） in the model of chronic obstructive pulmonary disease （COPD）, in the lungs of rats. Methods： Male Wistar rats were used to build up the model of COPD. Rats were randomly divided into the control group and model group, the IL-4 group and the dexamethasone group. The expressions of COX-2, PDGF-A and PDGF-B in the lung tissue were detected by western blotting and RT-PCR. Results： The expressions of COX-2, PDGF-A and PDGF-B in the model group were increased significantly. Those expressions in the IL-4 and dexamethasone group were notably decreased. Conclusion： IL-4 and dexamethasone could interfere in the establishment of COPD. The expressions of COX-2 and PDGF in the lung tissue of COPD were increased significantly and IL-4 and dexamethasone could decrease those expressions.     

血小板生长因子与子痫前期发病的关系

目的 探讨血小板生长因子(PDGF)在子痫前期(Preeclampsia,PRE)发病中的作用,进一步阐明PRE发病机制.方法 研究对象为13例正常晚孕妇女,20例重度PRE晚孕患者.运用酶联免疫吸附法测定两组研究对象血清PDGF-BB含量;原位杂交技术检测两组胎盘蜕膜血管PDGF-B mRNA的表达.PDGF-BB血清含量及PDGF-B mRNA蜕膜血管表达强度灰度值间行直线相关分析.结果 PDGF-BB含量在正常晚孕组为(39.6l±18.20)pg/ml,在重度PRE晚孕组为(83.54±34.52)pg/ml,两组比较差异有显著性(P＜0.001);重度PRE组胎盘蜕膜血管PDGF-B mRNA大量表达,强度明显高于对照组(P＜0.001).PDGF-BB血清含量及蜕膜血管表达强度灰度值呈明显负相关(r=-0.603,P＜0.001).结论 PRE患者血清PDGF-BB明显升高,蜕膜血管PDGF-B mRNA表达增强,说明PDGF可能参与了PRE胎盘血管病变,参与PRE病情发生发展.血清PDGF-BB水平升高可能与局部病变的蜕膜血管有关.     

The potential role of PDGF, IGF-1, TGF-β expression in idiopathic pulmonary fibrosis

Ｉｄｉｏｐａｔｈｉｃｐｕｌｍｏｎａｒｙｆｉｂｒｏｓｉｓ (ＩＰＦ) ,ａｌｓｏｒｅｆｅｒｒｅｄａｓｃｒｙｐｔｏｇｅｎｉｃｆｉｂｒｏｓｉｎｇａｌｖｅｏｌｉｔｉｓ ,ｉｓａｐｒｏｇｒｅｓｓｉｖｅｉｎｔｅｒｓｔｉｔｉａｌｌｕｎｇｄｉｓｅａｓｅｏｆｕｎｋｎｏｗｎｅｔｉｏｌｏｇｙ Ｃｏｎｖｅｎｔｉｏｎａｌｔｒｅａｔｍｅｎｔｗｉｔｈｃｏｒｔｉｃｏｓｔｅｒｏｉｄｓａｎｄｉｍｍｕｎｏｓｕｐｐｒｅｓｓｉｖｅｔｈｅｒａｐｙｈａｓｂｅｅｎｄｉｓａｐｐｏｉｎｔｉｎｇ 1　Ｉｎｆｉｌｔｒａｔｉｏｎｂｙｉｎｆｌａｍｍａｔｏｒｙｃｅｌ…     

抑制NF-κB对PDGF-A、PDGF-B在糖尿病大鼠肾组织表达的影响

目的:研究糖尿病大鼠肾组织血小板源性生长因子-A(PDGF-A)、血小板源性生长因子-B(PDGF-B)、核因子-κB(NF-κB)的表达,以及NF-κB抑制剂PDTC对其表达的影响。方法:将30只健康Wistar雄性大鼠随机分成3组:正常对照组(NC组)、糖尿病组(DM组)和糖尿病PDTC干预组(DP组),每组各10只。8周末收集大鼠24h尿测定微量白蛋白,处死大鼠取出肾脏称重,计算尿微量白蛋白排泄率(UAER)、肾重指数(KWI)并用免疫组化方法测定PDGF-A、PDGF-B、NF-κB的含量。结果:8周末,DM组和DP组的UAER、KWI较NC组明显升高;DP组较DM组明显下降。DM组肾组织NF-κB和PDGF-B的表达较NC组显著增高,DP组较DM组明显下降,但显著高于NC组;三组大鼠肾组织PDGF-A的表达均无显著性差异。结论:糖尿病大鼠肾组织局部表达的PDGF-B、NF-κB明显增加,抑制NF-κB能明显降低PDGF-B表达。提示NF-κB和PDGF-B可能在糖尿病肾病发生发展中起重要作用。     

自由基促进猪内皮细胞c－sis mRNA／PDGF－B链蛋白表达的实验研究

采用免疫组织化学和原位杂交方法，研究自由基（ＦＲ）对猪主动脉内皮细胞（ＥＣ）的ｃ－ｓｉｓｍＲＮＡ及血小板源生长因子（ＰＤＧＦ）Ｂ链蛋白表达的影响。结果显示，ＦＲ促进ｃ－ｓｉｓｍＲＮＡ和ＰＤＧＦ－Ｂ链蛋白的表达。ＥＣ暴露于ＦＲ２０ｍｉｎ，ｃ－ｓｉｓｍＲＮＡ和ＰＤＧＦ－Ｂ链蛋白的表达较对照组分别增加１．０和２．２倍。提示，ＦＲ损伤ＥＣ所诱导的ＰＤＧＦ合成增多在动脉粥样硬化的发病过程中可能起重要作用。     

大鼠急性脊髓损伤后血小板衍化生长因子-B的表达

目的:探讨血小板衍化生长因子-B(PDGF-B)在脊髓损伤(SCI)后对脊髓功能恢复的作用。方法:健康雌性SD大鼠48只随机分为免疫组化组(30只)和反转录-聚合酶链反应(RT-PCR)组(18只)。麻醉后,用改制的Ⅱ型纽约大学装置建立大鼠脊髓急性损伤模型。用免疫组化检测急性SCI后不同时段PDGF-B在脊髓中的表达,用RT-PCR检测PDGF-B的mRNA在急性SCI后不同时段表达的变化。结果:①PDGF-B蛋白表达:急性SCI后24 h,PDGF-B在损伤区周围神经元的表达开始增加(5.92±3.23),并于7 d后维持在一定水平,14 d后PDGF-B阳性细胞数增多,28 d达高峰(85.00±13.49),主要表达于坏死区增生的神经胶质细胞。②PDGF-B mRNA表达:SCI后1 d,PDGF-B mRNA表达降低,3 d接近正常,随后略有下降,14 d后mRNA表达升高,28 d基本回到正常。结论:急性SCI后,PDGF-B对损伤脊髓的功能恢复有重要作用。     

RNA干扰沉默STAT3对胶原诱导大鼠类风湿性关节炎的治疗作用

目的: 研究小干扰RNA(siRNA)干扰沉默信号转导和转录激活因子3(STAT3)对大鼠类风湿关节炎(RA)的治疗作用,评价其有效性,为RA的基因治疗提供实验依据。方法: 采用鸡Ⅱ型胶原诱导方法建立大鼠 RA(CIA)模型,实验分为正常组(非关节炎大鼠)、模型组(不给予治疗的关节炎大鼠)、阴性对照组(给予乱码RNA的关节炎大鼠)和治疗组(给予STAT3特异干扰siRNA的关节炎大鼠),实验中siRNA均由慢病毒颗粒包载。实验期间观察大鼠一般情况,每7 d检测大鼠关节病变程度并记录,实验第35天处死大鼠后观察其关节病理切片并进行评分;Western blotting法检测大鼠滑膜组织中STAT3蛋白表达水平;RT-PCR法检测大鼠滑膜组织中STAT3 mRNA表达水平。结果: 与模型组和阴性对照组比较,治疗组大鼠临床及形态学表现均明显减轻。与正常组比较,模型组和阴性对照组大鼠滑膜组织中STAT3 mRNA和蛋白表达水平明显增加(P<0.05或P<0.01),治疗组差异无统计学意义(P>0.05);模型组与阴性对照组比较差异无统计学意义(P>0.05)。与模型组比较,治疗组大鼠滑膜组织中STAT3 mRNA和蛋白表达水平明显下降(P<0.05)。结论: 局部注射siRNA阻断STAT3的表达可明显改善RA大鼠关节的组织病理学表现,其机制可能与STAT3 mRNA和蛋白表达水平降低有关。     

Effect of valsartan on the expression of angiotensin II receptors in the lung of chronic antigen exposure rats

Background Many studies have suggested that angiotensin Ⅱ （Ang Ⅱ） and its receptors may be involved in the development of asthma. However, the expression of angiotensin Ⅱ receptors （AGTR） is not clear in the lung tissue of chronic asthmatics. This study was designed to determine the relationship between airway remodeling, dysfunction and the expression of AGTRs in a rat model of asthma. Methods Rats were sensitized with ovalbumin （OVA） for 2 weeks. Sixty minutes before an inhalation challenge, the rats were pretreated either with valsartan （15, 30, 50 mg.kg-1.d-1） or saline intragastrically. Then the rats received an OVA challenge for 30 alternative days. Acetylcholine （Ach）-induced bronchoconstriction was measured after the final antigen challenge. White cell counts in bronchoalveolar lavage fluid （BALF） and morphological changes in the airways were then assessed. The levels of transforming growth factor-beta 1 （TGF-β1） and platelet-derived growth factor （PDGF） in BALF were detected by ELISA. The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting. Results AGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls. The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness （mainly in small airways） in lungs of chronic antigen-exposed rats were positively correlated. Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats. However, AGTR2 mRNA and protein levels in the OVA-challenged rats and high-dose valsartan-treated rats （50 mg.kg-1.d-1） were also increased. Valsartan significantly decreased inflammatory cell accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats. Valsartan also decreased allergen-induced structural changes in rat airway （including total airway wall thickness and smooth muscle area） and the levels of TGF-β1 and PDGF in BALE Conclusions AGTR     

Effect of vaisartan on the expression of angiotensin II receptors in the lung of chronic antigen exposure rats

Background Many studies have suggested that angiotensin II (Ang II) and its receptors may be involved in the development of asthma.However,the expression of angiotensin II receptors (AGTR) is not clear in the lung tissue of chronic asthmatics.This study was designed to determine the relationship between airway remodeling,dysfunction and the expression of AGTRs in a rat model of asthma.Methods Rats were sensitized with ovalbumin (OVA) for 2 weeks.Sixty minutes before an inhalation challenge,the rats challenge for 30 alternative days.Acetylcholine (Ach)-induced bronchoconstriction was measured after the final antigen challenge.White cell counts in bronchoalveolar lavage fluid (BALF) and morphological changes in the airways were then assessed.The levels of transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) in BALF were detected by ELISA.The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting.Results AGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls.The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness (mainly in small airways) in lungs of chronic antigen-exposed rats were positively correlated.Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats.However,AGTR2 mRNA and protein levels in the OVA-challenged rats and accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats.Valsartan also decreased allergen-induced structural changes in rat airway (including total airway wall thickness and smooth muscle area) and the levels of TGF-β1 and PDGF in BALF.Conclusions AGTR1 expression is potentially associated with airway remodeling and dysfunction in asthma.Ang II and AGTR1 may participate in airway inflammation and airway remodeling of chronic antigen-exposed rats.Valsartan,a AGTR1 antagonist,could inhibit AGTR1 expression and partially inhibits structural airway changes as well as airway inflammation in chronic OVA-exposed rats.     

血小板激活因子致鼠肺循环和血小板生长因子分布变化的实验研究

本文观察正常鼠和注射血小板激活因子（PAF）后鼠肺动脉压和血小板生长因子（PDGF）-B链样物质分布的变化发现，注射PAF三周鼠肺动脉压较正常对照组显著升高（P〈0。001）；同时．注射PAF后在鼠肺动脉压升高的同时肺小动脉血管内皮和大动脉及支气管周围间质有．正常鼠所没有的PDGF-B链样物质分布。上述结果表明，在PAF致肺动脉压升高的同时伴随有肺内皮和间质细胞PDGF的合成增加，提示PDGF参与PAF所致肺血管的改建过程，并在其中起一定作用。     

ERK信号转导通路与PDGF-B对大鼠主动脉平滑肌细胞增殖的影响

目的探讨血小板源性生长因子(PDGF)和ERK受体阻断剂在PDGF诱导的大鼠主动脉平滑肌细胞增殖中的作用。方法健康SD大鼠90只,随机分为5组(正常对照组、单纯损伤组、AG组、PD组、AG+PD组),建立大鼠主动脉球囊损伤模型,利用相应的受体阻断剂Tyrphosin-AG1295和PD98059分别或联合阻断PDGF和ERK受体,于术后7、14及21 d 3个时相点取主动脉进行HE染色,观察PDGF和ERK受体阻滞剂对新生内膜增生的影响;逆转录聚合酶链反应(RT-PCR)技术检测PDGF-B mRNA和ERK1 mRNA在血管中的表达变化;免疫组化技术检测血管平滑肌细胞的增殖细胞核抗原(PCNA)的表达;观察各组中PDGF和ERK受体对PCNA表达的影响。结果单纯损伤组及各干预组PDGF-B mRNA在各时相点的表达差异无统计学意义(P>0.05);单纯损伤组血管平滑肌细胞PCNA的表达明显增强,各干预组与单纯损伤组比较,差异有统计学意义(P<0.05),但各干预组间PCNA表达差异无统计学意义(P>0.05)。结论 PDGF和ERK受体阻断剂能降低大鼠动脉平滑肌细胞增殖,ERK信号转导通路可能参与了PDGF诱导的大鼠主动脉平滑肌细胞增殖。     

血小板源性生长因子及其受体在类风湿性关节炎大鼠肺组织的表达及与风湿肺关系的探讨

目的：观察类风湿关节炎大鼠模型肺脏不同时间的病理变化、血小权源性生长因子（PDGF）及其受体的表达，探讨风湿肺发病机制。方法：Wistar大鼠用福氏完全佐剂致类风湿关节炎（RA）后，选择36只分别在不同时期和应用氢化考的松及低分子量肝素进行治疗后，取其肺脏观察HE染色病理变化及免疫组化染色检测PDGF配体及受体表达情况。结果：致炎模型15d时肺泡炎最严重，30d时肺纤维化最严重，PDGF配体及受体在正常肺组织中表达较少，RA15d时表达高峰，RA30d时有所回落。氢考和低分子量肝素治疗后明显下降。结论：风湿肺的变化经历了从肺泡炎至且纤维化的过程。PDGF配体及受体表达增高与风湿肺病理改变加重一致。低分子量肝素治疗风湿肺与氢化考的松具有同样作用，提示可用PDGF抑制剂控制风湿肺进展。     

Kawasaki Disease on PDGF Expression and VSMC Proliferation

The effect of serum of patients with Kawasaki disease (KD) on expression of platelet-derived growth factor (PDGF) B chain protein in vascular endothelial cells (VEC) was studied by immunocytochemical method. Meanwhile,the effects of the endothelial cell conditioned media (ECM) on expression of PDGF receptor mRNA in vascular smooth muscle cells (VSMC) and on cell cycle of VSMC were investigated by the methods of nucleic acid hybridization and flow cytometry (FCM). The results showed that the serum of patients with KD induced the expression of PDGF-B chain protein significantly. ECM significantly promoted the expression of PDGF receptor mRNA and induced the proliferation of VSMC. These data suggest that the activation of PDGF-PDGF receptor may play a role in the pathogenesis of coronary complication of KD.     

Effects of Tripterine on mRNA Expression of Oncogene c-myc and Platelet-Derived Growth Factor of Vascular Smooth Muscle Cells in Rats

Percutaneoustransluminalcoronaryangioplasty(PTCA)hasbecomeacommonlyemployedtechniqueinthetreatmentofcoronaryheartdiseaseoverthelastdecade.However,thefrequentoccurrenceofrestenosisfollowing30%to40%ofinitiallysuccessfulprocedureremainsthemajorlimitationofthetechnique(').Studiessuggestthatoverproliferationofvascularsmoothmusclecells(VSMCs),playingapredominantroleintherestenoticprocess,inwhichobviouslytheactivationofnuclearoncogenes(c--myc,etc)andincreaseofgrowthfactorsreleasedwithinthearterial…     

非限制性外支架对兔移植静脉血小板源性生长因子表达的影响

目的 探讨非限制性外支架防治移植静脉再狭窄的可能作用机制. 方法新西兰白兔随机分为支架组和对照组,每组18只.均实施颈外静脉-颈总动脉移植术,支架组在移植静脉外套以外支架(直径6 mm的人造涤纶血管),对照组无外支架.术后7、14、28 d每组各6只兔手术取出移植静脉,分别进行血小板源性生长因子B链(PDGF-B)免疫组织化学染色,计算PDGF-B阳性率;以RT-PCR方法检测PDGF-B mRNA的表达量. 结果支架组移植静脉内膜PDGF-B阳性率术后14、28 d均明显低于对照组(15.2%±3.6%vs 21.6%±4.6%,6.5%±2.6%vs 12.5%±4.4%,均P＜0.05);中膜阳性率术后7、14、28 d均明显低于对照组(13.8%±4.6%vs 25.4%±6.2%,21.3%±4.4%vs 35.7%±7.3%,7.2%±3.2%vs 19.2%±5.4%,均P＜0.01);外膜阳性率术后28 d达高峰,而对照组在术后14 d达高峰,28 d时支架组阳性率明显高于对照组.RT-PCR检测显示术后7、14、28 d 2组移植静脉均可见PDGF-B特异条带(457 bp),各时间点支架组PDGF-B mRNA的表达均明显低于对照组(31.2%±6.5%vs 45.4%±8.4%,P＜0.05;42.3%±6.2%vs 65.2%±11.5%,P＜0.01;21.3%±5.6%vs 36.2%±9.4%,P＜0.01). 结论抑制移植静脉PDGF合成、改变PDGF分布规律可能是非限制性外支架防治移植静脉再狭窄的作用机制之一.     

脑缺血肺损伤大鼠肺组织trkB的表达变化

目的 观察脑缺血肺损伤大鼠肺组织酪氨酸蛋白激酶B（trkB）的表达变化, 并探讨其与肺损伤的关系。 方法 成年SD大鼠分为假手术组和脑缺血肺损伤组,每组13只动物。术后3 d处死大鼠,每组中5只取肺组织进行免疫组化染色、8只取肺组织进行RT-PCR和Western blot,检测trkB蛋白在肺组织的分布、trkB mRNA和蛋白的表达变化。 结果 trkB分布于气管上皮和平滑肌。与假手术组相比,trkB mRNA和蛋白在损伤肺组织表达增加（P<0.05）。 结论 脑缺血肺损伤大鼠肺组织trkB表达水平明显上调,提示其与脑缺血肺损伤有关。     

野百合碱致鼠肺动脉高压形成时肺PDGF分布变化的实验研究

本研究观察了野百合碱(MCT)作用后不同时间鼠肺动脉压变化时其肺内PDGF-B链样物质分布的变化;实验结果显示,正常对照组肺动脉压为(1.73±0.01)kPa,肺内未见有PDGF-B链样物质分布:MCT作用后1、2、3周组鼠肺动脉压分别为(2.72±O.05)、(2.93±0.01)和(3.31±0.08)kPa;同时,在鼠肺血管及支气管间质内可见有PDGF-B链样物质分布。结果表明,在MCT致鼠肺动脉压力升高的同时可伴有肺间质细胞合成和分泌PDGF增多,后者可能在MCT诱发肺血管改建和肺动脉高压形成过程中具有一定作用。     

血小板衍生生长因子-B的表达与根尖周骨吸收的关系

目的:观察血小板衍生生长因子B链(PDGF-B)在大鼠根尖周炎中的表达情况,探讨PDGF-B与根尖周骨吸收的关系。方法:将24只SD大鼠开髓,分别于术后7,14,21,28 d取下颌骨,制备组织切片,用免疫组织化学的方法测定PDGF-B在大鼠根尖周炎中的表达,酶组织化学方法检测抗酒石酸酸性磷酸酶,观察破骨细胞。结果:在根尖周炎的急性期,即术后7 d和14 d,PDGF-B阳性细胞和破骨细胞都增多,二者存在明显正相关;在根尖周炎的慢性期,即术后21 d和28 d,PDGF-B表达继续增高,而破骨细胞数却迅速下降,二者为负相关。结论:PDGF-B在根尖周炎早期可能主要发挥促骨吸收作用,而在慢性期,PDGF-B可能主要与根尖周炎的修复相关。