不同剂量野百合碱诱导SD幼鼠右室阻力负荷性心力衰竭模型的比较

目的采用不同剂量野百合碱(monocrota line,MCT)诱导SD幼鼠右心衰竭模型,探讨适合的右心衰竭模型制作方法。方法清洁级SD雄性幼鼠125只,随机分为G0、G1、G2、G3、G4组,每组各25只SD幼鼠。G1～G4组幼鼠分别一次性腹腔注射MCT 30、40、50、60 mg/kg,诱导制作右心衰竭动物模型;G0组为对照组,给予生理盐水腹腔注射。腹腔注射后每2周1次,采用彩色多普勒超声仪测SD幼鼠右心室横径、三尖瓣反流速度、肺动脉压、射血分数(EF值)、缩短分数(FS值),共检测6周,4次;随后处死SD幼鼠,取心脏、肺组织病理切片对比观察。结果 G0组SD幼鼠无死亡,G1、G2、G3组SD幼鼠的死亡率远远低于G4组。各组SD幼鼠右心室横径逐渐增大,G1～G4组较G0组更明显(P<0.01);G0组SD幼鼠各时期的三尖瓣反流速度、肺动脉压无明显改变,而G1～G4组逐渐增高(P<0.01)。G1组SD幼鼠肺动脉仅出现轻度新生内膜病变,心脏组织病理切片无明显改变;G2组SD幼鼠肺动脉可见较明显新生内膜病变,心脏组织病理切片可见明显炎性细胞浸润;G3、G4组SD幼鼠肺组织病理切片可见中小动脉中膜明显增厚和小动脉肌化,部分肺组织远端小动脉闭塞,肺泡内可见心衰细胞,右室心肌细胞肥大伴纤维组织增生。结论 50 mg/kg MCT可成功诱导建立肺动脉高压致右心衰竭模型,其病理变化可更好模拟重度肺动脉高压致右心衰竭,且实验动物有较高的生存率。     

柯萨奇病毒B3病毒性心肌炎小鼠心肌组织微小RNAl初始体和连接蛋白43的表达

目的 观察柯萨奇病毒B3(CVB3)病毒性心肌炎(VMC)小鼠心肌组织微小RNA1初始体(pri-miRNA-1)和连接蛋白43(Cx43)的表达变化,探讨VMC室性心律失常的发生机制.方法 4周龄雄性Balb/c小鼠70只随机分为VMC组40只(14 d和28 d2个亚组各20只)和对照组30只(14 d和28 d2个亚组各15只).VMC组腹腔注射CVB3Nancy株悬液0.1 mL,对照组腹腔注射不含病毒的RPMI 1640培养基0.1 mL.2组小鼠分别在接种第14、28天无痛苦处死,取心室肌,采用反转录聚合酶链反应(RT-PCR)检测其心室肌组织pri-miRNA-1、dicer1 mRNA的表达,免疫组织化学法检测其Cx43的表达.结果 1. VMC组14 d和28 d小鼠心室肌组织pri-miRNA-1表达水平均显著高于对照组(0.82±0.04 vs 0.64±0.01,0.79±0.03 vs 0.62±0.01 Pa<0.01);2.VMC组14 d和28 d小鼠心室肌组织dicer1 mRNA表达水平均显著高于对照组(0.91±0.03 vs 0.72±0.02,0.87±0.02 vs 0.71±0.02 Pa<0.01);3.VMC组小鼠心室肌组织炎性病灶中变性、坏死周围心肌细胞Cx43表达明显减弱,甚至阴性,分布不规则,VMC组14 d和28 d亚组Cx43蛋白表达均显著低于对照组(0.27±0.01 vs 0.42±0.02,0.22±0.02 vs 0.44±0.02 P.<0.01);4.VMC组小鼠心室肌组织pri-miRNA-1表达水平与Cx43蛋白水平呈显著负相关(r=-0.798 P<0.01),与dicerl mRNA表达水平呈显著正相关(r=0.828 P<0.01).结论 VMC小鼠心肌组织pri-miRNA-1和dicer1参与了CVB3的发生机制,dicer1表达升高可能通过促进miRNA-1生成、抑制Cx43的表达促进室性心律失常的发生.实用儿科临床杂志,2009,24(10):754-756     

基质金属蛋白酶及其抑制物在容量过负荷致慢性心力衰竭大鼠血浆及心肌组织中的变化及意义

目的 观察容量过负荷致慢性心力衰竭大鼠血浆及心肌组织基质金属蛋白酶-8(MMP-8)及其抑制物-1(TIMP-1)的表达变化,探讨其在慢性心力衰竭发病中的病理生理作用.方法 雄性SD大鼠17只,随机分为分流组(n=9)和对照组(n=8).分流组通过腹主动脉下腔静脉穿刺术建立容量过负荷致慢性充血性心力衰竭动物模型,对照组大鼠除不做穿刺外,余操作过程同分流组.分别测定2组大鼠心功能及血流动力学指标,检测血浆MMP-8及TIMP-1水平,实时荧光定量PCR测定大鼠左心室、右心室MMP-8 mRNA、TIMP-1 mRNA的表达.结果 术后8周,分流组大鼠左心室收缩压、左心室舒张压、左心室内压差、左心室内压最大上升速率及最大下降速率较对照组明显降低(Pa＜0.05,0.01);左心室舒张末压较对照组明显升高(P＜0.05).分流组大鼠血浆MMP-8、TIMP-1水平均较对照组明显升高(Pa＜0.05).与对照组相比,分流组大鼠左心室心肌组织MMP-8 mRNA及左、右心室心肌组织TIMP-1 mRNA水平均有升高趋势,右心室MMP-8 mRNA水平有下降趋势,但2组比较差异均无统计学意义(Pa＞0.05);左心室和右心室心肌组织中MMP-8/TIMP-1明显降低,右心室较左心室下降更明显.结论 MMP-8与TIMP-1通过影响胶原代谢,参与容量过负荷致慢性充血性心力衰竭的病理生理过程.     

奥卡西平对戊四氮致癫(癎)幼鼠海马胶质纤维酸性蛋白表达的影响

目的 探讨奥卡西平(OXC)对慢性癫(癎)幼鼠海马星形胶质细胞表达胶质纤维酸性蛋白(GFAP)的影响.方法 50只21日龄SD幼年雄性大鼠,随机分为5组:A组(阴性对照组)、B组(阳性对照组)、C组(OXC低剂量组)、D组(OXC中剂量组)、E组(OXC高剂量组),每组10只.A组每日腹腔注射等量9g·L-1盐水;B组腹腔注射戊四氮(PTZ)40 mg·kg-1·d-1;C～E组腹腔注射PTZ 40 mg·kg-1·d-1后分别予OXC 100 mg·kg-1、OXC 200 mg·kg-1、OXC 300 mg·kg-1灌胃.连续用药21 d,观察幼鼠体质量、行为学表现;采用免疫组织化学方法检测幼鼠海马GFAP阳性星形胶质细胞的表达;应用实时荧光定量PCR方法检测幼鼠海马组织中GFAP mRNA表达.结果 与A组相比,其他各组幼鼠均有癫(癎)发作,海马组织中均发现GFAP阳性细胞数量增多(P＜0.01),GFAP mRNA的表达增加(P＜0.01);与B组相比,C～E组幼鼠癫(癎)发作潜伏时间延长,发作级别低,点燃率低(Pa＜0.05),GFAP阳性细胞数量逐渐减少(P＜0.05),GFAP mRNA表达降低(P＜0.05);与其他各组相比,E组幼鼠体质量增长缓慢(P＜0.05).结论 OXC对PTZ点燃的慢性癫(癎)引起的脑损伤有保护作用,其程度与剂量有关,但大剂量OXC会抑制幼鼠生长;OXC的这种神经保护作用可能是通过抑制星形胶质细胞表达GFAP实现的.     

右心衰竭幼龄大鼠B型钠尿肽的变化及卡维地洛的干预作用

目的：通过研究右心衰竭幼龄大鼠血清B型钠尿肽（BNP）含量、右室心肌BNP蛋白和BNP mRNA 表达的变化及β受体阻滞剂卡维地洛的干预作用,探讨BNP在小儿右心衰竭的诊断和治疗中的意义。方法：51只Sprague Dawley 4周龄大鼠随机分为4周心衰组、6周心衰组、卡维地洛组、4周对照组和6周对照组。心衰组及卡维地洛组大鼠给予腹腔注射野百合碱（MCT）,两个对照组给予腹腔注射生理盐水。至4周形成右心衰竭模型,将4周心衰组和4周对照组幼龄大鼠处死观察心肌病理学变化,同时卡维地洛组开始给予卡维地洛灌胃共14 d,6周心衰组和6周对照组同时等量蒸馏水灌胃至6周。每组存活大鼠测血流动力学和相关生理指标, ELISA法检测血清中的BNP水平,免疫组化法和RT-PCR法检测右室心肌BNP蛋白和BNP mRNA的表达。结果：4周心衰组血清BNP浓度、右室心肌中BNP蛋白、BNP mRNA与4周对照组相比均明显升高(P<0.01),6周心衰组上述指标升高更为显著(P<0.01)。血清BNP、心肌BNP蛋白之间具有正相关关系(P<0.01)。卡维地洛组与6周心衰组比较血流动力学改善,右室肥厚减轻,血清BNP浓度、心肌中BNP蛋白和BNPmRNA表达均降低(P<0.05)。结论：右心衰竭时BNP可作为诊断和反映心衰严重程度的指标,卡维地洛对治疗压力负荷性右心衰竭有一定作用。［中国当代儿科杂志,2009,11（7）：571-576］     

缝隙连接蛋白43在扩张型心肌病大鼠心肌中的表达及其与左室射血分数的相关性

目的探讨缝隙连接蛋白43(Cx43)在扩张型心肌病(DCM)模型大鼠左侧心室肌的表达及其与左心室射血分数(LVEF)的相关性。方法应用多柔比星腹腔注射建立DCM大鼠模型;分别于造模成功当时(8周末)、造模4周后(12周末)检测正常对照组、DCM组的LVEF,留取左侧心室肌检测Cx43 mRNA表达和免疫组化观察Cx43的分布。结果与对照组比较,DCM组在8周末、12周末Cx43 mRNA、Cx43平均灰度值及LVEF均明显下降,12周末下降最明显,差异均有统计学意义(P均0.05)。Cx43 mRNA、平均灰度值与LVEF呈正相关(r=0.91、0.89,P均0.01)。结论 DCM大鼠心肌Cx43表达明显减少且分布紊乱,Cx43可能参与了DCM的病理过程。     

高脂饮食对幼鼠生长及胰岛素样生长因子表达的影响

目的研究高脂饮食对幼鼠生长及胰岛素样生长因子(IGF-I)表达的影响,闸明血清和肝脏组织IGF-I代谢紊乱与非酒精性脂肪性肝病(NAFLD)幼鼠生长迟缓的关系。方法 21日龄SD雄性大鼠40只,随机分成正常(N)组、高脂(HF)组。高脂饮食成功诱导NAFLD幼鼠造模成功后,测定血清IGF-I及胰岛素样生长因子结合蛋白-3(IGFBP-3)水平,采用RT-PCR与Western-blot检测肝脏IGF-I和IGFBP3的mRNA和蛋白表达。结果5周高脂饲料喂养后,高脂组幼鼠肝脏符合典型的NAFLD病理特征;与正常组相比,高脂组血清总胆固醇(TC)、血清高敏C反应蛋白、血清ALT及肝组织三酰甘油(TG)含量均显著升高(P均<0.01)。高脂组幼鼠体质量、鼻-尾长度较正常组增长缓慢(P<0.01)。胫骨长度和股骨长度两组差异无统计学意义;高脂组股骨的骨密度和骨矿含量均低于正常组(P均<0.05)。高脂组幼鼠血清IGF-I和IGFBP-3均较正常组表达显著下降(P均<0.01);血清生长激素(GH)两组差异无统计学意义(P>0.05);高脂组肝脏组织IGF-I和IGFBP3 mRNA和蛋白表达水平与血清学结果一致。结...     

钙调神经磷酸酶信号通路介导大鼠慢性缺氧致右心室心肌凋亡的机制

目的研究钙调神经磷酸酶(CaN)介导慢性缺氧致右心室心肌凋亡的作用机制。方法SD大鼠30只分为慢性缺氧组、环孢素处理组(CsA,10 mg.kg-1.d-1,腹腔注射)及正常对照组。慢性缺氧组、CsA处理组大鼠均置于缺氧仓内连续缺氧21 d(95～105 mL.L-1O2),正常处理组常温常压常氧饲养21 d。3组大鼠均取右心室,行右心室心肌组织石蜡切片,观察心脏形态学,Western blot及RT-PCR检测各组右心室心肌凋亡指数(AI)、CaNβ亚基(CnAβ)蛋白及mRNA、凋亡蛋白Bcl-2蛋白及mRNA和激活T细胞核因子3(NFAT3)蛋白水平。结果1.缺氧21 d后,CsA处理组大鼠凋亡指数(AI)显著高于慢性缺氧组(P<0.01),且慢性缺氧组AI显著高于正常对照组(P<0.01)。2.慢性缺氧组大鼠右心室心肌CnAβ蛋白及mRNA表达、NFAT3蛋白水平均高于正常对照组及CsA处理组(Pa<0.01)。3.CsA处理组凋亡蛋白Bcl-2蛋白和mRNA表达水平均显著低于慢性缺氧组(Pa<0.01),且慢性缺氧组凋亡蛋白Bcl-2 mRNA表达和蛋白水平也均显著低于正常对照组(Pa<0.05)。...     

瑞舒伐他汀对右心衰竭幼鼠右心功能的影响

目的观察瑞舒伐他汀对野百合碱致右心衰竭SD幼鼠血流动力学及心肺病理的影响。方法清洁级SD雄性幼鼠140只,体质量90~100 g,随机分为4组,G1、G2、G3及G0对照组,每组各35只幼鼠,G1、G2、G3组幼鼠按50 mg/kg剂量,一次性腹腔注射野百合碱(MCT)溶液,G0组予等体积生理盐水一次性腹腔注射,同时G2组予瑞舒伐他汀片5mg/(kg.d)灌胃,G3组从第5周始予瑞舒伐他汀片5mg/(kg.d)灌胃。注射MCT后每2周选取5只幼鼠,采用彩色多普勒超声仪测定幼鼠右室横径、三尖瓣反流速度及肺动脉压力,随后处死大鼠,取心脏、肺组织做病理切片对比观察。结果除第2周外,第4、第6周时各组幼鼠的右室横径、三尖瓣反流速度、肺动脉压力的差异均有统计学意义(P<0.01)。G1组幼鼠心肺组织病理切片可见中小动脉中膜明显增厚和小动脉肌化,部分肺组织远端小动脉闭塞,肺泡内可见心衰细胞,右室心肌细胞肥大伴纤维组织增生,炎细胞浸润明显。G2、G3组与G1组幼鼠相比病理变化较轻,其中G2组接近正常。结论瑞舒伐他汀可减缓幼鼠肺动脉高压致右心衰竭的进展过程。     

黄芪对扩张型心肌病大鼠心肌缝隙连接蛋白43表达的影响

目的探讨黄芪对扩张型心肌病(DCM)大鼠心肌缝隙连接蛋白43(Cx43)表达的影响。方法应用多柔比星腹腔注射建立DCM大鼠模型;模型组大鼠按照不同的给药方法随机分为黄芪组和模型对照组,黄芪组应用黄芪颗粒加双蒸馏水灌胃,模型对照组和正常对照组用定量的双蒸馏水灌胃,三组均1次/d灌胃4周。12周末超声测量各组大鼠心脏左心室射血分数(LVEF),逆转录聚合酶链反应法检测Cx43 m RNA,采用免疫组化方法观察Cx43分布。结果与模型对照组比较,黄芪组大鼠心肌Cx43m RNA、Cx43平均灰度值、LVEF均增高,差异均有统计学意义(P均0.05);黄芪组较模型对照组心肌Cx43的分布紊乱有改善。结论黄芪能改善DCM大鼠心肌Cx43表达和分布,并能改善其心功能。     

Cardiac atrial natriuretic peptide in monocrotaline-induced pulmonary hypertensive rats

To determine the time course and potential triggers for synthesis of atrial natriuretic peptide (ANP) in right ventricle during the development of right ventricular hypertrophy (RVH), we measured mean right atrial pressure, right ventricular systolic pressure (RVSP), immunoreactive ANP (iANP) concentrations in plasma, and cardiac iANP concentrations and contents of monocrotaline (MCT)-induced pulmonary hypertensive rats treated with a subcutaneous injection of MCT (40 mg/kg). Following the development of RVH and pulmonary hypertension, iANP concentrations in plasma and iANP concentrations and contents in ventricular tissues increased with time. At the third week after treatment, iANP concentrations in MCT rats increased 6-fold in plasma, 57-fold in the right ventricular free wall, 20-fold in the ventricular septum and 10-fold in the left ventricular free wall compared with those in controls. At the third week, iANP contents of total ventricular tissues in MCT and control rats were 29% and 0.8%, respectively, of the corresponding atrial contents. The iANP concentrations and contents of right ventricular free walls in MCT rats were greater than those of any other parts of ventricular tissues. The iANP concentrations in right ventricular free walls were very closely related to RVSP (r = 0.93, P < 0.001). In MCT rats, iANP concentrations in right atrial tissues decreased with time. This study shows that ventricular ANP contributes to the amount of ANP stored within the heart in MCT rats and that pressure overload may be one of the triggers for ANP synthesis in the right ventricle.     

幼鼠慢性压力负荷性心力衰竭中心肌细胞凋亡的变化及卡维地洛的防治作用

目的　观察幼鼠心脏后负荷过高的慢性心力衰竭 (CHF)发展中心肌细胞凋亡变化及卡维地洛的防治作用。方法　采用腹主动脉缩窄术建立幼鼠CHF模型 ,术后 4周随机分 3组 :假手术对照组、CHF组、卡维地洛预防组。卡维地洛直接灌胃给药 ,8周后行血流动力学、心肌病理分析、心肌细胞凋亡及其相关基因Bcl 2、P53 蛋白表达水平。结果　与假手术组比较 ,CHF组左室收缩压 (LVSP)、左室舒张末压 (LVEDP)、左、右心室相对重量 (LVRW ,RVRW )、凋亡指数 (AI)、P53 基因蛋白表达水平显著升高 (P <0 .0 1) ,左室内压最大收缩率( +dp/dtmax)、左室内压最大舒张率 ( -dp/dtmax)、Bcl 2基因蛋白表达水平均显著降低 (P均 <0 .0 1)。与CHF组比较 ,卡维地洛组LVSP、LVEDP、LVRW、RVRW、AI、P53 基因蛋白表达水平下降 ,+dp/dtmax、-dp/dtmax、Bcl 2基因蛋白表达水平显著升高 (P <0 .0 1)。结论　心肌细胞凋亡在CHF发展过程中起重要作用。卡维地洛可降低心肌细胞凋亡发生及相关基因Bcl 2、P53 异常表达     

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??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.     

Expression of Connexin 43 in the hearts of rat embryos exposed to nitrofen and effects of vitamin A on it

Rats with experimental congenital diaphragmatic hernia (CDH) have heart hypoplasia and conotruncal and great vessel malformations that are likely related to disturbed neural crest developmental control. Neural crest cells communicate through intercellular gap junctions whose main protein is Connexin 43 (Cx43). The migration and participation of neural crest cells in heart development is likely influenced by this protein which might be also directly involved in myocardial development. Vitamin A is beneficial for heart hypoplasia in CDH rats. The aims of this study were to examine the status of Cx43 in the heart of embryonal rats exposed to nitrofen and to assess if vitamin A reverts these effects. Pregnant rats received either 100 mg nitrofen or olive oil on E9.5. Each group was divided into two subgroups according to the subsequent treatment with intragastric vitamin A (15,000 i.u.) or vehicle on E10.5 and E11.5. The pups were recovered on E13, E15, and E21 and the hearts were dissected out and pooled. Cx43 mRNA expression was determined by quantitative real-time PCR. Comparisons among groups were made with ANOVA and Bonferroni post hoc tests with a threshold of significance of P<0.05. In control rats Cx43 mRNA was minimally expressed on E13 and E15 and fully expressed on E21. Nitrofen significantly increased Cx43 mRNA on E15. Additional treatment with vitamin A tended to moderate this increase on E15. Cx43 was overexpressed in the hearts of nitrofen-exposed embryonal rats on day E15 of gestation. Vitamin A tended to normalize this expression. The mechanism of action of Cx43 deserves further investigation.     

Value of prostaglandin E1 in cardiac malformations in the newborn infant

Prostaglandin E1 (PGE1) was administered to increase ductus patency in 26 neonates who present a cyanotic heart disease with right ventricular obstruction (1st group, 13 cases) or congestive heart failure with left ventricular outflow obstruction (2nd group, 13 cases). Clinical improvement occurred in all but the oldest infant in the first group. The efficacy of PGE1 is inconstant in the second group, but medical status was very poor before treatment. We could usually reduce the dose of PGE1 but in no case we could stop the drug before surgery. Surgery could be delayed several hours or days to get an hemodynamic and biologic satisfactory condition and even a few weeks until the infants and their pulmonary arteries had grown (1st group). Side effects are common but relatively minor.     

卡托普利联合经鼻持续呼吸道正压给氧治疗左向右分流型先天性心脏病并肺炎心力衰竭的疗效

目的探讨卡托普利联合经鼻持续呼吸道正压(CPAP)给氧治疗左向右分流型先天性心脏病(先心病)并肺炎心力衰竭(心衰)的疗效。方法将在本院儿科住院治疗的左向右分流型先心病并肺炎心衰患儿108例,随机分为对照组、观察组、CPAP组3组,3组基础治疗相同,对照组采用(面罩或鼻导管)普通给氧,CPAP组采用经鼻CPAP,观察组在CPAP组基础上加用卡托普利治疗。结果观察组与CPAP组肺部啰音消失时间比较差异有统计学意义(P<0.01),气促呼吸困难消失、心率正常、肝脏回缩时间比较差异亦均有统计学意义(Pa<0.05);观察组与对照组气促呼吸困难消失、心率正常、肝脏回缩、肺部啰音消失时间比较差异均有统计学意义(Pa<0.01);CPAP组与对照组气促呼吸困难消失、心率正常、肝脏回缩、肺部啰音消失时间比较差异均有统计学意义(Pa<0.05)。观察组血浆氨基末端脑利钠肽前体水平降低均明显优于CPAP组和对照组(Pa<0.01),CPAP组和对照组比较其血浆氨基末端脑利钠肽前体水平降低无明显差异性。结论卡托普利联合经鼻CPAP治疗左向右分流型先心病并肺炎心衰时可产生有益的血流动力学效应,减少左向右分流量,快速缓解心衰症状,延缓心室重塑,降低患儿病死率,改善预后。     

雷公藤甲素对实验性肺动脉高压肺脏基质金属蛋白酶MMP2和MMP9的影响

目的：雷公藤甲素能缓解实验性大鼠肺动脉高压,该实验观察雷公藤甲素对肺动脉高压血管重构模型的影响并探讨与基质金属蛋白酶的关系。方法：60只SD大鼠随机分为6组：①正常对照组;②模型组;③连续治疗组;④连续治疗组的安慰剂对照组;⑤延迟治疗组;⑥延迟治疗组的安慰剂对照组。术后5周通过心导管术测得血液动力学指标,并用弹力纤维染色观察肺小动脉的病理学变化。用免疫组织化学染色显示MMP2 和MMP9在肺血管上的阳性分布和半定量,荧光定量PCR（FS-PCR）行肺组织MMP2和MMP9的定量。结果:平均肺动脉压(m PAP） 为38.10±1.20 vs 16.70±1.16 mmHg和心室重量变化［RV/(LV+S)%］为（62.45±5.28）% vs （22.76±3.01）%及血管阻塞积分(VOS） 1.736±0.080 vs 0.000±0.000,②组较①组明显增高(P<0.01);MMP2和MMP9的表达量在肺血管壁(MMP2为 1.48±0.35 vs 0.00±0.00; MMP9 1.95±0.22 vs 0.00±0.00)和肺组织(MMP2 0.85±0.67 vs 5.50±0.67. MMP9 0.85±0.67 vs 4.95±0.69)均显示②组较①组明显增高（P<0.05）;雷公藤甲素连续治疗组和延迟治疗组各指标均较模型组和各自的安慰剂组减低,且连续治疗效果更好（mPAP 20.80±1.03 vs 26.20±1.03 mmHg,P<0.05）。结论: 雷公藤甲素能延缓大鼠左肺切除加野百合碱注射诱导的肺动脉高压和右心室肥厚,并能抑制新生内膜形成,可能与抑制MMPs的活性增高有关。［中国当代儿科杂志,2007,9（5）：479-483］     

心力衰竭幼鼠心肌结缔组织生长因子的表达及药物干预研究

目的研究心力衰竭(heartfailure,HF;简称心衰)幼鼠心肌结缔组织生长因子(connectivetissuegrowthfactor,CTGF)表达及苯那普利的调节作用。方法采用腹主动脉缩窄术建立幼鼠HF模型,术后6周经高频超声筛查将符合心衰标准的幼鼠随机分为HF组和苯那普利治疗组,另设假手术组。苯那普利治疗组灌胃给药4周,术后10周时行高频超声、心肌重量分析、免疫组化和逆转录-聚合酶链反应分别检测心肌功能、心室重构程度、心肌CTGF表达。结果10周时于3组中各随机抓取15只幼鼠进行检测。与假手术组比较,HF组左室舒张末期内径(LYEDD)、左室收缩末期内径(LVESD)、室间隔舒张末期内径(IVSTd)、室间隔收缩末期内径(IVSTs)、左室后壁舒张末期厚度(LVPWTd)、左室后壁收缩末期厚度(LVPWTs)、左心室相对质量(LVRW)、右心室相对质量(RVRW)均升高(P<0.01),而短轴缩短率(FS)、射血分数(EF)降低(P<0.01).CTGF免疫阳性细胞增多,CTGFmRNA表达亦高[(0.609±0.065)vs(0.117±0.011),P<0.01]。苯那普利组与HF组相比LVESD,IVSTd,IVSTs,LVPWTd,LVPWTs,LVRW,RVRW降低(P<0.01),FS、EF升高(P<0.01),CTGF免疫阳性细胞减少,CTGFmRNA表达下降[(0.441±0.053)vs(0.609±0.065),P<0.01]。结论HF幼鼠心肌CTGF表达明显上调,苯那普利可部分抑制HF心肌CTGF的表达,从而抑制HF时心室重构的发生,改善心脏功能。