肾小球滤过屏障超微结构改变与Alport综合征蛋白尿的关系

 目的:探讨肾小球滤过屏障超微结构改变与Alport综合征（AS）蛋白尿发生的关系。方法:AS患者35例,男24例,女11例,肾活检的年龄为1.17~24岁。根据尿蛋白结果将患者分为2组：无/间歇性蛋白尿组（13例）和持续性蛋白尿组（22例）。测量AS肾小球基底膜（GBM）变薄、增厚和致密层撕裂分层的长度,计算其各占GBM总长度的百分比;根据平均足突宽度（FPW）= π／4×（∑基底膜长度／∑足突个数）计算患者足突宽度。分析比较2组患者GBM变薄、增厚、致密层撕裂分层比例和平均FPW及其与AS蛋白尿的关系。结果:持续性蛋白尿组GBM增厚、致密层撕裂分层比例和平均FPW较无/间歇蛋白尿组高（均P<0.05）。平均FPW与GBM增厚、致密层撕裂分层及肾活检年龄均呈正相关（均P<0.01）。结论: AS患者GBM病变程度越重,足突融合越严重,蛋白尿越严重,提示AS基底膜异常有可能通过影响足突及裂孔膜的结构和功能导致蛋白尿发生。     

肾缺血再灌注大鼠蛋白尿的生成及NO的作用

目的:探讨肾缺血再灌注(I-R)损伤时排出尿蛋白的量和质的变化以及一氧化氮(NO)在其中的作用。方法:在肾I-R大鼠模型上,用考马斯亮蓝比色法测定尿蛋白含量,SDS-PAGE分析尿液中蛋白种类的改变,硝酸还原酶法测定肾组织NO含量。并观察硝普钠(SNP)、L-硝基精氨酸(L-NNA)和氨基胍(AG)对尿蛋白的影响。结果:肾I-R损伤导致大鼠产生明显蛋白尿(P＜0.01),而且出现了分子量大于白蛋白(66kD)的蛋白质,肾I-R后肾组织的NO的增多与尿蛋白排出量密切相关(r=0.704,P＜0.01),SNP使I-R大鼠尿蛋白排出增多,AG、L-NNA使I-R大鼠尿蛋白排出减少。结论:肾I-R导致肾小球滤过膜通透性增加及蛋白尿产生,NO是蛋白尿形成的重要因素之一。     

足细胞损伤与肾小球疾病

足细胞（podocyte），即肾小球脏层上皮细胞，它附着于肾小球基底膜（glomerular basement membrane，GBM）的外侧，连同GBM和毛细血管内皮细胞一起，构成肾小球血液滤过屏障。足细胞这一独特的解剖位置，使得其体内研究较为困难；又由于正常成年机体的肾脏足细胞是一种终末分化细胞，体外培养的原代细胞不能增殖，     

慢性代谢性酸中毒显著诱导大鼠系膜细胞的增殖

目的：研究慢性代谢性酸中毒对大鼠肾小球体积、系膜细胞增殖、基质表达的影响及分子机制。 方法： 采用0.28 mol/L NH4Cl喂饲大鼠构建大鼠慢性代谢性酸中毒模型。采用光镜结合图像分析软件观察和分析大鼠肾小球结构。从肾皮质分离大鼠肾小球，肾小球增殖细胞核抗原(PCAN)和p27的表达采用免疫组化和/或Western blotting检测。肾皮质纤维连接蛋白(FN)ｍRNA的表达采用荧光定量RT-PCR检测。分别采用［3H］-TdR掺入法和ELISA方法检测了慢性酸负荷对体外培养的大鼠系膜细胞增殖及FN合成的影响。 结果： 各时点实验组大鼠动脉血pH、［HCO3-］均显著低于对照组(P<0.01)。第3、7、14 d实验组大鼠肾重及肾/体重比值均显著大于对照组，而绝对体重与对照相比无显著差异；平均肾小球面积、肾小球丝球体面积、球内细胞总数以及系膜区细胞数均大于对照组（P<0.05），第14 d大鼠肾小球系膜区面积与肾小球丝球体面积比值高于对照组（P<0.05）；第3、7、14 d Western blotting检测实验组大鼠肾小球PCNA表达增加，p27表达下调，免疫组织化学检测显示肾小球内阳性PCNA细胞主要位于系膜区；第7 d、14 d大鼠肾皮质FN mRNA的表达显著高于对照组（P<0.01）。体外系膜细胞［3H］-TdR掺入量随酸负荷强度而增高，酸负荷24 h和48 h，系膜细胞上清中FN含量显著增高。 结论： 慢性代谢性酸中毒能够诱导大鼠肾小球肥大、系膜细胞增生及细胞外基质增多，其机制与系膜细胞周期调控蛋白P27的表达下调有关。本研究为慢性代谢性酸中毒参与慢性肾小球疾病的硬化提供了体内和体外证据。     

Podocalyxin与糖尿病肾病的关系

足细胞标记蛋白(podocalyxin)作为足突顶端质膜的主要构成部分,是足突顶膜区主要的带负电荷的唾液酸蛋白,参与维持足细胞的正常结构和滤过屏障。糖尿病肾病早期以肾脏肥大和肾小球高滤过为特征。在肾小球足细胞的检测中,podocalyxin作为最常用的标记蛋白之一,对监测肾小球疾病的发生和发展起到极其重要的作用。深入研究podocalyxin对糖尿病肾小球病变的早期诊断及治疗有着重要的指导意义。     

儿童激素耐药肾病综合征相关致病基因及其临床检测策略

肾病综合征（NS）是因肾小球滤过屏障受损而引起的一绀临床综合征。肾小球滤过屏障由内皮细胞、基底膜和足细胞构成。多项研究表明,足细胞在肾小球滤过屏障中起关键作用,特别是足细胞相邻足突构成的裂隙膜（slitcliaphragm,SD）[1-4]。依据对激素治疗的反虚可将Ns分为激素敏感型（SSNS）和激素耐药型（SRNS）[5]。     

慢性阻塞性肺疾病大鼠肺泡巨噬细胞延迟整流钾通道的活性研究

目的：探讨慢性阻塞性肺疾病（COPD）模型大鼠肺泡巨噬细胞延迟整流钾通道（KV）活性变化。 方法： 随机将大鼠分为COPD模型组和对照组,采用香烟烟雾吸入法复制大鼠COPD模型。应用全细胞电压或电流膜片钳的方法，观察和比较正常对照大鼠与COPD模型大鼠肺泡巨噬细胞（AM）KV电流活性、膜电位和电容的差异。 结果： （1）COPD组支气管肺泡灌洗液（BALF）中单个核细胞总数及AM细胞数均显著高于对照组(P<0.01)；（2）COPD大鼠BALF中AM细胞Kv电流幅度［（520.5±38.7） pA，+50 mV,n=30］显著低于对照组［（713.6±44.4） pA，+50 mV,n=30，P<0.01］；（3）COPD组AM细胞电容［（101.6±7.6）pF, n=42］与对照组［（97.4±1.6）pF,n=67］无显著差异(P>0.05)。但模型组AM膜电位［（-24.6±4.5） mV，n=18］负值显著低于对照组［（-37.9±6.1） mV,n=34，P<0.01］。 结论： COPD大鼠肺泡AM细胞KV功能下调，细胞膜电位负值降低，兴奋性升高。该机制可能与AM细胞促进COPD发病的形成机制有关。     

大鼠足细胞损害后肾小球血管生成素的异常表达及其意义

 目的：探讨大鼠足细胞损害后，内源性血管生成素的异常变化及其在进行性肾小球硬化中的病理作用。方法: 选择柔红霉素诱导足细胞损害的大鼠模型作为研究对象，80只健康雄性Wistar大鼠，随机分为假手术(sham)组25只、单侧肾切除(UNx)组25只和UNx ＋柔红霉素（DRB）组30只。DRB组大鼠，摘除左肾后的第7、14 d，从尾静脉注射柔红霉素5 mg·kg-1各1次。然后，分别于造模后的第1、2、4、6、8周，随机取各组大鼠5只，收集24 h尿量，采血取肾，检测24 h尿蛋白定量（24hUPQ）、血肌酐（Scr）和尿素氮（BUN），用PAS染色、免疫组化、原位杂交和透射电镜技术进行病理形态学分析。结果: DRB组的24hUPQ、BUN、Scr显著高于相同时点的sham组和UNx组；肾小球硬化指数（GSI）随病变的进展逐步升高。免疫组化和原位杂交显示，DRB组的肾小球表达Ang1 mRNA和Ang1蛋白下调，表达Ang2 mRNA和Ang2蛋白上调。电镜显示，DRB组逐步出现严重的足细胞损害。Sham组和UNx组的肾小球没有病理改变。DRB组的Ang1 mRNA表达与Ang2 mRNA表达呈负相关；Ang1蛋白表达与Ang1 mRNA表达呈正相关，与Ang2蛋白表达、四型胶原（CoIV）蛋白表达、GSI 、24hUPQ、Bun、Scr呈负相关； Ang2蛋白表达与Ang2 mRNA表达、CoIV蛋白表达、GSI 、24hUPQ、BUN 、Scr之间呈正相关。结论: 足细胞损伤可能是导致肾小球内Ang1和Ang2表达失衡的主要原因，Ang1表达下调，失去对Ang2的抑制，使Ang2表达上调，并介导肾小球滤过膜通透性增高和肾小球硬化的形成。     

银杏叶提取物对2型糖尿病大鼠肾脏结构和功能的影响

目的：研究银杏叶提取物（GBE）对2型糖尿病（T2DM）大鼠肾脏结构和功能的影响。方法：SD大鼠随机分为正常对照组、高脂组、糖尿病组（高脂饮食+STZ造模）及糖尿病GBE治疗组（GBE 8 mg·kg-1·d-1），8周后处死大鼠,检测体重、肾重、尿量、24 h尿蛋白和N-乙酰-β-氨基葡萄糖苷酶(NAG)水平；电镜观察肾脏超微结构；RT-PCR法测定基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶组织抑制因子-1（TIMP-1）、Ⅳ型胶原的基因表达水平。结果：糖尿病组大鼠肾皮质TIMP-1、Ⅳ型胶原mRNA表达高于正常对照组，MMP-9 mRNA表达低于正常对照组，肾重指数、尿量、24 h 尿蛋白、NAG均高于对照组。电镜下见肾小球基底膜增厚，厚薄不均匀，足细胞突起肿胀，变短，并可见足突融合，球囊壁层细胞内线粒体扩张，肾小球内胶原纤维增多。而糖尿病GBE治疗组肾小球基底膜及足细胞病变明显较轻，肾皮质MMP-9表达高于糖尿病组，Ⅳ型胶原mRNA表达低于糖尿病组，尿量、24 h尿蛋白、NAG均低于糖尿病组。TIMP-1 mRNA表达无明显差异。结论：GBE可改善2型糖尿病大鼠肾脏的结构和功能，其作用机制与降低TIMP-1、Ⅳ型胶原mRNA表达，升高MMP-9 mRNA表达，阻止ECM的堆积有关。     

巢蛋白在阿霉素肾病模型大鼠肾组织中表达及霉酚酸酯的干预作用

背景：研究证明,足细胞损伤是产生肾小球性蛋白尿的重要机制。而关于足细胞内众多骨架蛋白如何互相调节维持足细胞特有的形态目前尚未完全了解,足细胞骨架的构建和重塑也成为蛋白尿发生机制的研究热点。 目的：构建阿霉素微小病变肾病大鼠模型,以霉酚酸酯进行干预,检测大鼠肾组织中巢蛋白(nestin)的表达。 方法：纳入雄性Wistar大鼠36只,随机均分为肾病模型组、霉酚酸酯组、正常组(n=12)。肾病模型组、霉酚酸酯组大鼠一次性尾静脉注射阿霉素进行造模,正常组尾静脉注射等量生理盐水。霉酚酸酯组大鼠于造模次日给予霉酚酸酯灌胃,20 mg/(kg•d),1次/d;其他两组大鼠每日给予等量生理盐水。各组分别于造模后14,21,28 d各处死4只大鼠,取肾皮质进行苏木精-伊红染色和免疫组化染色,观察大鼠肾组织病理学改变以及nestin表达情况。 结果与结论：正常组大鼠肾小球滤过膜结构完整,上皮细胞足突清晰;肾病模型组大鼠肾小球上皮细胞足突广泛融合,基底膜正常;霉酚酸酯组大鼠肾小球上皮细胞足突部分融合,但病变较轻。免疫组化结果提示从造模第14天开始,肾病模型组和霉酚酸酯组大鼠nestin表达明显增加,与正常组比较差异有显著性意义(P < 0.05);霉酚酸酯组大鼠nestin表达低于肾病模型组,差异有显著性意义(P < 0.05)。提示肾小球足细胞损伤时,足细胞内nestin表达增多,随病情加重而表达增高。霉酚酸酯可以减轻足细胞损伤,下调nestin的表达,维持足细胞的正常结构,达到延缓肾脏损害的目的。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程      

Glomerular anionic site distribution in nonproteinuric rats. A computer-assisted morphometric analysis.

The cationic ultrastructural tracer polyethyleneimine (PEI: pI approximately equal to 11.0), binds electrophysically to uniformly spaced discrete electron-dense anionic sites present in the laminae rarae of the rat glomerular basement membrane (GBM), mesangial reflections of the GBM, Bowman's capsule, and tubular basement membranes when administered intravenously. Computer-assisted morphometric analysis of glomerular anionic sites reveals that the maximum concentration of stainable lamina rara externa (lre) sites (21/10,000 A GBM) occurs 60 minutes after PEI injection with a site-site interspacing of 460 A. Lamina rara interna (lri) sites similarly demonstrate a maximum concentration (20/10,000 A GBM) at 60 minutes with a periodicity of 497 A. The concentration and distribution of anionic sites within the lri was irregular in pattern and markedly decreased in number, while the lre possesses an electrical field that is highly regular at all time intervals analyzed (15, 30, 60, 120, 180, 240, and 300 minutes). Immersion and perfusion of renal tissue with PEI reveals additional heavy staining of the epithelial and endothelial cell sialoprotein coatings. PEI appears to bind to glomerular anionic sites reversibly: ie, between 60 and 180 minutes the concentration of stained sites decreases. At 300 minutes, the interspacing once again approaches the 60-minute concentration. This suggests a dynamic turnover or dissociation followed by a reassociation of glomerular negatively charged PEI binding sites. In contrast, morphometric analysis of anionic sites stained with lysozyme and protamine sulfate reveals interspacings of 642 A and 585 A, respectively; in addition, these tracers produce major glomerular ultrastructural alterations and induce transient proteinuria. PEI does not induce proteinuria in rats, nor does it produce glomerular morphologic alterations when ten times the tracer dosage is administered intravenously. These findings indicate that the choice of ultrastructural charge tracer, the method of administering the tracer, and the time selected for analysis of tissue after administration of tracer significantly influences results. Morphometric analysis of the distribution of glomerular anionic sites in nonproteinuric rats provides a method of evaluating quantitative alterations of the glomerular charge barrier in renal disease models.     

Anionic sites in the human kidney: ex vivo perfusion studies

Heparan sulfate-proteoglycan (HS-PG) anionic sites located in the glomerular basement membrane (GBM) are thought to contribute to glomerular permselectivity in man. The number and distribution of HS-PG anionic sites in the GBM and mesangial matrix of seven normal human kidneys and three kidneys from children with congenital nephrotic syndrome (CNS) were evaluated by ex vivo perfusion of polyethyleneimine (PEI; Mr 40,000 to 60,000). In the normal kidneys lamina rara externa (LRE) anionic sites (21.8 +/- 2.4 per 1000-nm actual GBM length) were well labeled and similar to those obtained by immersion staining of fixed tissue with Mr 1200 PEI. Lamina rara interna (LRI) anionic site number (22.0 +/- 2.6 per 1000-nm GBM) and appearance were better demonstrated by PEI perfusion than by the immersion technique. PEI perfusion also demonstrated regularly arranged (60 to 120 nm apart) mesangial matrix anionic sites (20- to 30-nm diameter) at 4.09 +/- 0.59 x 10(3) sites per nm2 matrix. PEI perfusion of three kidneys from children with CNS demonstrated decreased (16.3 +/- 1.9 per 1000-nm GBM) LRE anionic sites and normal LRI anionic sites (22.0 +/- 3.5 per 1000-nm GBM). Mesangial volume was increased, and mesangial anionic sites were less frequent (3.24 +/- 0.42 x 10(3) per nm2 matrix) and irregular in size in the children with CNS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-dependent movement of cationic molecules across the glomerular wall

Different concentrations of the polycation polyethyleneimine (PEI) were administered by single intravenous injections or by constant vascular perfusion to the kidneys of Sprague-Dawley rats. At a fixed time interval after administration of PEI, the kidneys were fixed and the distribution of PEI in the glomerular wall was evaluated by electron microscopy. At the lower concentrations (e.g., 0.005%), PEI bound only to the glomerular endothelial glycocalyx and preferentially to microvillous projections on this endothelium. At higher concentrations (e.g., 0.05%), PEI also bound to discrete anionic sites in the lamina rara interna (LRI) but was rarely seen in the lamina rara externa (LRE). As the concentration of PEI was further increased (e.g., 0.5%), PEI moved deeper into the glomerular basement membrane (GBM) and bound extensively to discrete anionic sites in the lamina rara externa. Although anionic sites in the LRI and LRE appeared nearly saturated following infusion of 0.5% PEI, this cationic molecule was rarely seen to cross filtration slits and pass into the urinary space. At still higher concentrations (e.g., 2%), however, PEI moved freely across the filtration slits, bound extensively to the glomerular epithelial glycocalyx, and induced a narrowing of the filtration slits. When PEI was mechanically perfused through the kidney vasculature for 3 minutes, PEI binding to the epithelial glycocalyx caused very extensive adherence of adjacent podocyte processes and the narrowing and loss of filtration slits. Also in these latter samples, discrete anionic sites in the LRE were no longer apparent and a dense band of PEI was seen under the foot processes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in glomerular heparan sulfate in puromycin aminonucleoside nephrosis.

Changes in glomerular anionic sites in puromycin aminonucleoside nephrosis (PAN) in the rat are controversial. The authors examined glomerular anionic sites in PAN by in vivo staining with polyethyleneimine (PEI). They also quantitated and characterized glomerular heparan sulfate (HS), which is known to be a major glomerular polyanion in PAN, using in vivo incorporation of 35S-sulfate. PAN rats had a mean protein excretion of 96 +/- 23 mg per 24 hours. Staining of anionic sites with PEI showed 15.3 +/- 2.8 sites per 1000-nm length of glomerular basement membrane in controls, 13.7 +/- 1.9 sites in PAN rats (P greater than 0.05), and 50% of rats with early PAN had absent staining. Total 35S-sulfate incorporation was similar in both the controls and established PAN rats (2900 +/- 150 dpm/mg dry wt of glomeruli versus 3005 +/- 260, P greater than 0.05) but decreased in early PAN rats (2025 +/- 148). The percentage of 35S-sulfate incorporated into chondroitin sulfate was similar in all three groups of animals. HS uronic acid was also similar (1.8 +/- 0.2 g/mg dry wt of glomeruli versus 1.7 +/- 0.3, P greater than 0.05) but decreased in early PAN (1.1 +/- 0.2). The distribution of 35S-sulfate activity within the HS subfractions was examined by ion-exchange chromatography and showed a shift in percent present from 1.0 M to 1.25 M fraction in established and early PAN animals (control 1.0 M 37% +/- 3.2% versus PAN 19% +/- 3.4%, P less than 0.01, and 1.25 M 36% +/- 2.9% versus 53% +/- 2.9%, P less than 0.01). These results demonstrate that glomerular heparan sulfate is unchanged in established PAN but decreased in early PAN. SO4 incorporation is unchanged in established PAN and diminished in early PAN. Thus, early in PAN HS synthesis is impaired, but in established PAN the HS is normal, and changes in glomerular HS cannot explain the increased permeability.     

Changes in thickness and anionic sites of the glomerular basement membrane after subtotal nephrectomy in the rat.

Rats progressively develop proteinuria and glomerular sclerosis with age. These physiologic and histologic changes are accelerated by subtotal renal mass ablation. Alterations in the glomerular basement membrane (GBM), such as thickening and decreased anionic site density, occur during senescence. This study examines the ultrastructural alterations of the GBM affecting remnant glomeruli. Six week-old male Wistar rats underwent a subtotal nephrectomy (70%) and were compared with sham operated rats. Rats were fed a standard diet, and physiologic measurements were performed every 3 weeks. Rats were killed 6 and 12 weeks after surgery. Anionic sites were labeled by polyethyleneimine perfusion before killing. Kidneys were processed for light and electron microscopy. Nephrectomized rats had higher protein-uria than the controls and developed glomerular sclerosis. The GBM of nephrectomized rats were significantly thinner and anionic sites were less numerous 12 weeks after nephrectomy, especially in the lamina densa (LD) of the GBM. The number and distribution of anionic sites were similar to those observed in sham operated rats killed 6 weeks after surgery. These results indicate that glomerular sclerosis and GBM thickening are unrelated phenomena. They also suggest that the number and density of anionic sites in LD are not a prominent factor for increasing proteinuria after subtotal nephrectomy.     

Glomerular basement membrane anionic charge site changes early in aminonucleoside nephrosis.

Alterations of glomerular basement membrane (GBM) anionic (charge sites, CSs) in the development of proteinuria in a model of idiopathic nephrotic syndrome in man (puromycin aminonucleoside nephrotic syndrome [PAN] in the rat) were assessed quantitatively and sequentially early after disease induction. GBM CSs (known to consist mainly of heparan sulfate-rich proteoglycans) were stained in vivo and, in a separate group of animals by an in vitro method, with the cationic marker polyethyleneimine (PEI) studied by electron microscopic examination. Four hours after administration of PAN, there was a significant decrease in GBM lamina rara externa CSs: 18 +/- 0.7 versus 22.0 +/- 2.2 per 1000 nm GBM in controls by PEI injection and 17.2 +/- 2.7 versus 21.1 +/- 1.6 per 1000 nm GBM in controls by PEI in vitro staining. This CS alteration coincided with changes in glomerular epithelial cell morphologic characteristics (increased cytoplasmic organelles and rough endoplasmic reticulum) and preceded the detection of foot process broadening (at 24 hours) and increased urinary albuminuria (suggested at 12-24 hours, statistically significant at 36-48 hours). These results suggest that GBM CS-heparan sulfate proteoglycan alterations consisting of either decreased number and/or less anionic charge occur early in PAN and support a role for glomerular epithelial cell maintenance of GBM CS for normal glomerular function.     

肝细胞生长因子对大鼠局灶性脑缺血/再灌注损伤的保护作用

目的:研究肝细胞生长因子(HGF)对大鼠局灶性脑缺血/再灌注损伤的影响。方法:Sprague-Dawley大鼠随机分为3组,即假手术组(Sham组),脑缺血/再灌注组(I/R组),HGF处理组(HGF +I/R组)。采用线栓法制备大鼠大脑中动脉闭塞模型。再灌注24h后,进行神经功能评分,测定脑梗死灶体积,检测超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:I/R组大鼠出现不同程度的神经功能障碍,缺血侧脑组织见较大的梗死灶(231.15±22.79 mm3),脑组织SOD活性(83.10±17.16 U/mgPro)明显降低、MDA含量(11.86±2.91μmol/gPro)显著增高(与Sham组比较,P0.01)。与I/R组比较,HGF+I/R组神经功能障碍明显改善、梗死灶体积(196.64±25.28 mm3)明显减小(P0.05),SOD活性(109.91±23.93U/mgPro)显著升高(P0.05)、MDA含量(7.49±2.27μmol/gPro)明显降低(P0.01)。结论:HGF对大鼠局灶性脑缺血/再灌注损伤具有保护作用,其机制可能与增强自由基清除能力,抑制脂质过氧化反应有关。     

X线照射增加大鼠心肌对缺血/再灌注损伤的敏感性*

 目的：观察胸部X线放射治疗大鼠对心肌缺血/再灌注损伤的敏感性。方法：用胸部单次照射X线20 Gy构建放射性心脏损伤模型,采用完全随机分组方法将Wistar大鼠分为假损伤组、损伤组、假损伤+假手术组、假损伤+缺血/再灌注组、损伤+假手术组和损伤+缺血/再灌注组,于创伤后2周行心肌缺血/再灌注。通过BL-410生物信号记录分析系统记录各组大鼠左心室发展压（LVDP）、左心室压力上升的最大速率（+dp/dtmax）和左心室压力下降的最大速率（-dp/dtmax）;采用ELISA方法检测大鼠血清心肌肌钙蛋白I（cTnI）和肌酸激酶同工酶（CK-MB）;用BI2000图像分析软件测定心肌梗死面积占总面积的百分比。结果：损伤+缺血/再灌注组离体心功能明显低于假损伤+缺血/再灌注组（P＜0.01）,损伤+缺血/再灌注组血清cTnI和CK-MB水平显著高于假损伤+缺血/再灌注组（P＜0.01）,损伤+缺血/再灌注组心肌梗死面积显著大于假损伤+缺血/再灌注组（P＜0.01）。结论:X线照射增加大鼠心肌对缺血/再灌注损伤的敏感性。     

Role of glomerular epithelial cell injury in the pathogenesis of glomerular scarring in the rat remnant kidney model.

We investigated the roles of glomerular epithelial cell (GEC) pathology and dysfunction in the pathogenesis of glomerular scarring and attempted to separate them from direct hypertensive injury in the 5/6 nephrectomy (RK) model of glomerular injury. Male WKY rats weighing 200 g were studied 6 weeks after RK, when approximately one-half had developed systemic hypertension (systolic blood pressure > or = 150 mm Hg) (HT), and one-half were normotensive (NT). The incidence of glomerular necrosis and scarring was greatest in the HT rats (P = 0.0259), and vascular necrosis was only seen in 4 of 11 HT rats. The RK group had increased glomerular diameters (HT, 174 mu mean; NT, 171 mu; sham, 142 mu; P = 0.0014 by analysis of variance). There was foot process effacement in the HT and NT groups (HT, 104 filtration slits/100 mu glomerular basement membrane; NT, 112 mu; sham, 143 mu; P < 0.005 by analysis of variance), but GEC separation from the glomerular basement membrane was not significant in either HT or NT rats. GEC function was determined from protamine-heparin aggregate disappearance curves, and the curves, representing GEC endocytosis, were not different in either HT or NT groups compared with the sham-operated groups. These findings suggest that GEC function is preserved in RK, and the changes in glomerular size and GEC morphology are nonlethal and adaptive. The morphological appearance of the acute glomerular and vascular lesions and their presence only in HT animals is consistent with a hypertensive pathogenesis. The glomerular sclerosis seen in both HT and NT may result from either resolution of acute lesions with scarring and/or adaptive changes in glomerular structure and cellular functions other than the GEC clearance function we studied.