转化生长因子β1在大鼠纤维化腹膜组织中的表达及作用

目的:检测转化生长因子β1在腹膜透析大鼠腹膜内表达,并探讨其在腹膜纤维化中的意义。方法:实验于2005-06/2006-03在中南大学湘雅二医院肾内科实验室完成。①实验材料:雄性SD大鼠,体质量180～240g,由中南大学湘雅二医院动物实验中心提供。②实验方法:将28只大鼠按随机数字表随机分为4组,每组7只。正常对照组不予任何干预;生理盐水组腹腔注射20mL生理盐水;低糖透析液组腹腔注射20mL1.5%葡萄糖透析液;高糖透析液组腹腔注射20mL4.25%葡萄糖透析液,均为1次/d。4周后,向大鼠腹腔注射4.25%葡萄糖腹膜透析液20mL,4h后于大鼠右下腹缓慢插入带有多个侧孔的10号静脉留置针,缓慢低位引流腹透液,量取引流液。③实验评估:取大鼠壁层腹膜组织,以苏木素-伊红染色,镜下测量腹膜厚度,采用免疫组织化学方法检测大鼠腹膜中转化生长因子β1及纤连蛋白。结果:28只大鼠均进入结果分析。①高糖透析液组、低糖透析液组超滤量均明显低于正常对照组与生理盐水组,并且高糖透析液组超滤量明显少于低糖透析液组(P均<0.05)。②高糖透析液组腹膜明显增厚,表面粗糙,间皮细胞肿胀,脱落,间皮下有大量血管生成以及胶原纤维沉积,还可见单核细胞等炎症细胞浸润,与其他组比较,腹膜厚度明显增加(P<0.05)。③高糖透析液组转化生长因子β1、纤连蛋白表达量均明显高于其他组;低糖透析液组转化生长因子β1、纤连蛋白表达量均明显高于正常对照组与生理盐水组(P<0.05)。④大鼠腹膜组织转化生长因子β1蛋白与纤连蛋白表达量、腹膜厚度之间呈明显的正相关(r=0.86,0.83,P<0.05)。结论:葡萄糖透析液可诱导腹膜组织转化生长因子β1明显上调,腹膜转化生长因子β1高表达与腹膜透析腹膜纤维化密切相关。     

血红素加氧酶-1对高糖诱导大鼠腹膜间皮细胞转化生长因子β1和纤维连接蛋白表达的影响

目的研究血红素加氧酶-1（HO-1）对高糖作用下体外培养的大鼠腹膜间皮细胞（RPMC）转化生长因子β1（TGF-β1）和纤维连接蛋白（FN）表达的影响。方法将原代培养的第3代RPMC随机分为对照组、高糖组、钴原卟啉（CoPP）＋高糖组和CoPP组。同步培养72h后,以反转录聚合酶链反应（RT-PCR）法检测各组细胞TGF-β1和FNmRNA表达情况;酶联免疫吸附法（ELISA）检测细胞上清液中TGF-β1和FN的蛋白质水平。结果高糖组、CoPP＋高糖组和CoPP组的HO-1mRNA及蛋白表达水平均显著高于对照组,其中CoPP＋高糖组显著高于高糖组;高糖组和CoPP＋高糖组的FNmRNA及蛋白表达水平显著高于对照组及CoPP组;高糖组、CoPP＋高糖组TGF-β1mRNA及蛋白表达水平显著高于对照组及CoPP组,其中CoPP＋高糖组显著低于高糖组。结论 HO-1可抑制高糖诱导的RPMCTGF-β1和FN的表达,具有抗腹膜纤维化的作用。     

SARA、TGF-β/Smad信号通路与腹膜纤维化的基因治疗

长期腹膜透析可导致腹膜纤维化,其主要特征是间皮细胞剥落和细胞外基质（ECM）的异常积聚所致的腹膜增厚,使腹膜透析效率降低。腹膜纤维化的产生是多种因素作用的结果,多种促纤维化细胞因子具有重要的调节作用,其中作用最为关键的是转化生长因子-β1（TGF-β1）。最近的研究显示,     

贝那普利对腹膜透析大鼠腹膜纤维化的影响

背景:已经证实血管紧张素转换酶抑制剂可延缓多种器官的纤维化.在慢性肾病中能降低蛋白尿,延缓肾硬化;在肝硬化中能改善肝脏微循环,抑制肝纤维化.但在腹膜透析中的腹膜纤维化是否具有相同的作用?作者未查及此类报道.目的:提出血管紧张素转换酶抑制剂贝那普利可以抑制腹膜透析治疗中腹膜纤维化的假设,并在实验过程中与正常组、模型组、阴性对照组比较.方法:将40只大鼠按随机数字表分为4组,每组10只:正常对照组不予任何干预:生理盐水组腹腔注射生理盐水;腹膜透析组腹腔注射20 mL 42.5 g/L葡萄糖透析液;腹膜透析合并用药组在腹腔注射42.5 g/L葡萄糖腹膜透析液20 mL同时口朋贝那普利片20 mg/(kg·d).腹腔注射均为1次/d,疗程4周.4周后,测量超虑量;取大鼠壁层腹膜组织,VG法染色光学显微镜观察腹膜厚度.结果与结论:40只大鼠中腹膜透析组2只死于腹膜炎,腹膜透析合并用药组1只不明原因死亡,共37只进入结果分析.与正常对照组、生理盐水组比较,腹膜透析组、腹膜透析合并用药组超滤量均显著下降(P均<0.05):与腹膜透析合并用药组比较,腹膜透析组超滤量明显减少(P<0.05).与正常对照组、生理盐水组、腹膜透析合并用药组比较,腹膜透析组腹膜厚度显著增加(P<0.05);腹膜透析合并用药组腹膜厚度较正常对照组明显增加(P<0.05).在大鼠维持性腹膜透析过程中,朋用贝那普利能有效保护腹膜超滤功能,减轻腹膜纤维化程度.     

高糖透析液对大鼠腹膜结缔组织生长因子表达的作用

目的探讨腹膜透析液对大鼠腹膜结缔组织生长因子（CTGF）的表达及细胞外基质（ECM）合成的影响。方法将中南大学湘雅二医院动物实验中心提供的SD大鼠随机分为4组：正常对照组（Con）、生理盐水组（NS）、低糖透析液组（LG）、高糖透析液组（HG）。4周后,评价腹膜的功能。VG染色镜下测量腹膜胶原组织厚度。免疫组织化学方法检测CTGF、TGF-β1及纤连蛋白（FN）蛋白质的表达。采用RT-PCR检测大鼠腹膜组织中CTGF和TGF-β1mRNA的表达。结果LG、HG组与Con、NS组相比较,超滤量均显著下降（P〈0.05）;HG组与LG组比较,其超滤量明显减少（P〈0.05）。D/Pcr的比较：HG组比Con、NS组升高（P〈0.05）;D/DO的比较：HG组比Con、NS组明显下降（P〈0.05）,LG组比Con组低（P〈0.05）。HG组腹膜胶原厚度比与其余各组均增厚（P〈0.05）;LG组比Con组增厚（P〈0.05）;HG组CTGF、TGF-β1、FN蛋白表达水平显著高于其他各组（P〈0.05）;LG组显著高于Con、NS组（P〈0.05）。在Con及NS组中,TGF-β1、CTGFmRNA呈低水平表达,TGF-β1、CTGFmRNA在HG组中表达最高（P〈0.05）。结论腹膜透析液尤其是高糖腹膜透析液,能明显诱导大鼠腹膜CTGF的表达增强,并促使腹膜纤维化发生。     

晚期氧化蛋白产物通过活性氧诱导人腹膜间皮细胞TGF-β1的表达

目的探讨晚期氧化蛋白产物（AOPP）诱导体外培养的人腹膜间皮细胞（HPMCs）对转化生长因子（TGF-β1）表达的影响及内源性活性氧（ROS）在此过程中的调节机制。方法体外制备AOPP-HSA模型，原代培养人腹膜间皮细胞。采用ELISA法检测TGF-β1蛋白水平，采用RT-PCR半定量分析HPYCs中TGF-β1 mRNA的基因表达水平，同时应用流式细胞仪检测细胞内活性氧的水平。结果AOPP-HSA能显著诱导人腹膜间皮细胞TGF-β1的分泌与基因表达，同时增加细胞内ROS的生成，呈时间与剂量依赖关系（P〈0．01），不同浓度的抗氧化剂维生素E和N-乙酰半胱胺酸预处理细胞，可明显地降低细胞内ROS的生成量，同时显著地抑制AOPP-HSA诱导人腹膜间皮细胞TGF-β1的分泌与基因表达，呈剂量依赖关系（P〈0．01），其中维生素E（50μmol／L）组和NAC（10mmol／L）组抑制更加显著。结论体外制备的AOPP可显著诱导人腹膜间皮细胞TGF-β1的分泌与基因表达，部分可能通过内源性ROS介导细胞内信号转导途径调节此过程，抗氧化剂维生素E和N-乙酰半胱胺酸可显著降低细胞ROS的生成量和显著抑制TGF-β1的分泌与基因表达。此研究揭示抗氧化剂在防治腹膜纤维化发生过程也许是一种可行的治疗策略。     

辛伐他汀对炎症状态下人腹膜间皮细胞促纤维化细胞生长因子TGF-β1和CTGF表达的影响

目的探讨辛伐他汀对体外培养的人腹膜间皮细胞在肿瘤坏死因子-a（tumor necrosis factor-a,TNF-a）诱导后转化细胞因子-β1（transforming growth factor-β1,TGF-β1）和结缔组织生长因子（connective tissue growth factor,CTGF）表达的影响。方法胰蛋白酶消化法从人腹膜组织中分离间皮细胞进行原代培养并传代,分为五组（每组设3个样本）：空白对照组（完全培养液）、单纯TNF-a（1000ng/L）诱导组和TNF-a（1000ng/L）诱导加低、中、高剂量辛伐他汀（2.5、5和10μmol/L）组。采用MTT（单四唑）检测各组间皮细胞的活性;半定量RT-PCR检测细胞内TGF-β1和CTGFmRNA表达;ELISA检测细胞上清液中TGF-β1和CTGF的蛋白质水平,细胞沉淀用BCA蛋白检测方法测定细胞蛋白质含量,用以校正ELISA结果。结果辛伐他汀能显著改善TNF-a诱导后人腹膜间皮细胞的活性（P〈0.05）,并能显著降低TNF-a诱导后人腹膜间皮细胞TGF-β1和CTGF的表达（P〈0.05）,两者在蛋白质和基因水平均呈剂量依赖关系。结论辛伐他汀能抑制炎症状态下人腹膜间皮细胞TGF-β1和CTGF的表达。     

反义基因对大鼠纤维化肝脏TGF—β受体表达的调节

探讨反义ＴＧＦ－βＲＮＡ调节其受体表达及防治肝纤维化的机制。方法本实验将反义ＴＧＦ－β１基因导入ＣＣｌ４诱导的大鼠纤维化肝脏，用原位杂交方法观察ＴＧＦ－β受体的表达。结果发现纤维化肝脏ＴＧＦ－βⅠ型受体主要分布于汇管区周围及纤维间隔内和散在分布于肝实质内，Ⅱ型受体则主要分布于肝脏实质肝细胞和纤维间隔及汇管区，且均较正常组明显。经转基因处理后大鼠纤维化肝脏Ⅰ、Ⅱ型受体的分布未发生改变，但阳性反应明显减弱，阳性细胞数量明显降低，且肝脏纤维间隔也明显减少，其中Ⅱ型受体阳性的肝细胞数量减少极为明显。结论反义ＴＧＦ－β１基因能下调其Ⅰ、Ⅱ型受体的表达，以阻止贮脂细胞的活化和肝细胞的凋亡，从而减缓肝纤维化的发展。     

川芎嗪防治腹膜纤维化作用的实验研究

目的探讨川芎嗪对实验性大鼠腹膜纤维化病变的影响和可能的机制。方法采用4.25%含糖透析液 脂多糖致腹膜纤维化模型。将大鼠随机分成3组:对照组、模型组、川芎嗪组,川芎嗪组在造模同时每日腹腔内注射川芎嗪40mg/kg。30天后处死各组大鼠,留取腹膜组织做HE及Masson染色,并留取血液和腹膜透析液做ELISA法测转化生长因子β。结果川芎嗪组的壁层腹膜厚度比模型组明显减轻,转化生长因子-β的浓度也明显下降。结论川芎嗪能有效的防治腹膜纤维化的进程。     

福辛普利对糖尿病大鼠肾皮质TGF-β1 mRNA表达的影响及意义

目的探讨福辛普利对糖尿病大鼠肾脏TGF-β1 mRNA表达的影响及其意义。方法采用链脲佐菌素(STZ)腹腔注射法建立糖尿病动物模型。结果与糖尿病组相比,福辛普利干预组的血糖、24 h尿蛋白排泄量、肾重指数显著减少、体重显著增加,差异有显著意义(P<0.01),并能使肾组织的病理改变明显减轻。结论福辛普利能减少糖尿病大鼠的尿蛋白排泄量,一定程度上降低血糖,抑制肾脏肥大、减轻肾脏的纤维化硬化程度。     

Effects of Smad7 overexpression on peritoneal inflammation in a rat peritoneal dialysis model.

OBJECTIVE: Transforming growth factor-beta (TGF-beta) has been shown to play a role in peritoneal complications due to long-term peritoneal dialysis (PD). In this study, we examined the effects of the TGF-beta signaling pathway on peritoneal inflammation associated with PD in rats by over-expressing Smad7, an inhibitor of TGF-beta/Smad signaling. METHODS: Peritoneal inflammation was induced in male Sprague-Dawley rats by intraperitoneal injections of 4.25% glucose dialysate (100 mg/kg body weight) daily for 4 weeks, with the addition of lipopolysaccharides (0.6 mg/kg body weight) on days 8, 10, 12, 22, 24, and 26. Peritoneal Smad7 gene transfer was achieved using an ultrasound microbubble mediated, doxycycline regulated, Smad7-expressing plasmid on day 0 and day 14 after initiation of PD. An empty vector was used as control. All rats were sacrificed after 4 weeks of PD. Peritoneal inflammatory response, including infiltration of total leukocytes (OX-1 positive) and macrophages (ED-1 positive) and expression of interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha), was examined by immunofluorescence and RT-PCR. RESULTS: After PD, peritoneal inflammation developed in control animals, as demonstrated by an increase in the number of OX-1-positive and ED-1-positive cells and upregulation of IL-1beta and TNF-alpha mRNA and protein expression. In contrast, in animals treated with Smad7 gene transfer, IL-1beta and TNF-alpha expression and OX-1-positive and ED-1-positive cell infiltration were significantly inhibited. Furthermore, prevention of peritoneal inflammation by overexpression of Smad7 was associated with inhibition of phosphorylation of Smad2/3, a downstream of the TGF-beta signaling pathway, as well as TGF-beta1 expression. CONCLUSION: Overexpression of Smad7 suppresses peritoneal inflammation induced by high glucose and lipopolysaccharides. The ability of Smad7 gene transfer to inhibit peritoneal inflammation indicates that targeting TGF-beta/Smad signaling may represent a new therapeutic strategy for the treatment of peritoneal complications associated with PD.     

长期腹膜透析患者腹膜保护策略

<正>长期腹膜透析可导致腹膜结构和功能损伤,小分子溶质转运和液体吸收增加,最终引起腹膜超滤失败,甚至发生包裹性腹膜硬化症(encapsulating     

Physiology of the peritoneum. Implications for peritoneal dialysis

Solute and water transport from blood to peritoneal cavity occur by diffusion and osmotic ultrafiltration, whereas absorption to blood via lymphatics negatively affects these two processes. This article delineates the physiology of peritoneal membrane and numerous factors that influence mass transport during peritoneal dialysis, thereby affecting its therapeutic efficacy. Benefits and limitations of continuous ambulatory peritoneal dialysis (CAPD) are discussed and compared to those of hemodialysis. Survival on CAPD, its complications and imperfections are reviewed in light of the widespread acceptance of the procedure.     

Effect of fluid supplementation and modality on peritoneal permeability characteristics in a rat peritoneal dialysis model.

OBJECTIVE: Hemoconcentration may influence peritoneal permeability parameters in anesthetized animals without fluid supplementation. Therefore, the aim of this study was to investigate the effects of fluid supplementation on peritoneal permeability in an acute peritoneal dialysis model in anesthetized rats. DESIGN: To study the effect of fluid supplementation on peritoneal permeability characteristics, 24 anesthetized male Wistar rats were investigated in 3 groups during a 4-hour standardized peritoneal permeability analysis with a 3.86% glucose dialysis solution (SPARa).The groups included a control group with no fluid supplementation (None, n = 8), a group with continuous subcutaneous infusion of 0.9% NaCl 3 mL/hr (SC, n = 9), and a group with continuous intravenous infusion of 0.9% NaCl 3 mL/hr (IV, n = 7). Inflow, sampling, and outflow of the dialysate during the SPARa occurred via a cannula inserted intraperitoneally in the lower left quadrant of the abdomen. Blood was drawn at the end of the dwell. Baseline blood samples were obtained from six separate untreated rats. RESULTS: Plasma osmolality was significantly lower in the IV group (334+/-1.4 mOsm/kg) compared to the None group (348+/-0.7 mOsm/kg, p < 0.01), and not different from the SC group (335+/-6.4 mOsm/kg), but higher than baseline (314+/-5.3 mOsm/kg, p < 0.001). Urine production during the dwell was not different among the groups: None 10.6+/-5.3 mL; SC 8.0+/-6.0 mL; and IV 10.5+/-5.6 mL. Transcapillary ultrafiltration after 4 hours was significantly higher in the IV group (p < 0.05) compared to the other two groups. Net ultrafiltration and effective lymphatic absorption were similar in all groups. Mass transfer area coefficient of urea (MTACurea) was significantly greater in the IV group (155+/-23.2 microL/minute, p < 0.003), but not different between the None (118+/-16.2 microL/min) and SC (123+/-25.9 microL/min) groups. Correcting these for the baseline plasma concentration resulted in higher values, but the IV data remained greater than the SC and None groups (p < 0.01).The glucose absorption, albumin, and IgG clearances and the sieving of sodium were alike in all groups. CONCLUSION: It can be concluded that IV fluid supplementation is more effective in preventing dehydration than SC supplementation, and it enhanced some peritoneal permeability characteristics in anesthetized rats during a 4-hour investigation. It is therefore important to standardize fluid supplementation in experiments with anesthetized animals.     

褪黑素对子宫内膜异位症大鼠细胞因子及NK细胞活性的作用

目的:观察褪黑素对大鼠子宫内膜异位症模型细胞因子及自然杀伤(NK)细胞活性的影响。方法:采用手术移植法制备大鼠子宫内膜异位症模型,大鼠随机分为正常对照组、模型对照组和褪黑素高、低剂量组,测定大鼠的血清TNF-α、IL-6、IL-8及脾脏NK细胞活性。结果:褪黑素治疗组与模型组相比血清TNF-α、IL-6、IL-8活性明显降低,脾脏NK细胞活性显著增高。结论:褪黑素对子宫内膜异位症大鼠具有治疗作用,其作用机制可能与其抑制TNF-α、IL-6、IL-8以及增强脾脏NK细胞活性有关。     

腹腔注射法建立一氧化碳中毒迟发性脑病大鼠模型

目的探索建立一氧化碳(CO)中毒迟发性脑病(DNS)大鼠模型的可靠方法。方法成年Wistar大鼠随机分成4个实验组(每组n=10)和1个对照组(n=4),实验组分别按50、100、150和200 mL/kg腹腔内注射CO,对照组按200 mL/kg腹腔内注射空气。中毒后不同时间断尾取血,分光光度法检测碳氧血红蛋白(HbCO)变化。迷宫实验评估动物的智力状态,以正确上安全岛少于3次为DNS。TUNEL法原位检测大脑皮质、海马区细胞凋亡情况。结果各实验组注射CO后,大鼠呈现典型CO中毒表现,HbCO与CO注射剂量呈显著正相关(r=0.77,P<0.05)。50 mL/kg组和对照组无明显DNS表现;100 mL/kg组和150 mL/kg组大多数动物中毒后存活,约半数存活动物出现DNS表现,脑组织细胞凋亡率显著高于对照组。200 mL/kg组大多数动物中毒后死亡,存活动物DNS发生率和脑细胞凋亡数与100 mL/kg组和150 mL/kg组无显著差异。结论按100～150 mL/kg腹腔注射CO可有效建立DNS大鼠模型,具有简便、可靠、重复性好的特点,是一种非常理想的造模方法。     

S-adenosyl-L-methionine attenuates oxidative stress and hepatic stellate cell activation in an ethanol-LPS-induced fibrotic rat model

Previous studies report S-adenosyl-L-methionine (SAMe) can exert hepatoprotective effects. At present, the role of SAMe in affecting the activation and/or proliferation of hepatic stellate cells (HSCs) during alcohol-induced fibrotic disease progression is poorly understood. In the human disease state, chronic ethanol intake increases hepatic exposure to LPS and magnifies the hepatic insult leading to fibrosis and cirrhosis. In this study, we developed a "2-hit" ethanol-LPS fibrotic liver rat model with which to investigate the effects of SAMe as a hepatic antifibrotic treatment. Male rats were maintained on liquid diets containing either ethanol or isocalorically matched controls for 8 weeks. Animals received ethanol alone (E), ethanol concomitant with twice weekly LPS injections (EL), or ethanol, LPS, and daily SAMe injections. When using this model, SAMe-treated animals demonstrated significantly decreased fibrosis, oxidative stress, steatosis, and improved liver function versus the EL group. In addition, the EL group showed increased HSC activation, an effect that was abrogated by the addition of SAMe. Analysis of the transforming growth factor-beta (TGF-beta) signaling pathways demonstrated increased hepatic TGF-beta and Smad3 messenger RNA expression in the E and EL groups, which was inhibited in the presence of SAMe. Conversely, SAMe led to increased Smad7 (an inhibitor of TGF-beta signaling) messenger RNA expression. These data demonstrate chronic ethanol feeding combined with LPS induces liver fibrosis, and the addition of SAMe significantly reduces hepatic injury and fibrosis through inhibition of oxidative stress and HSC activation.     

羧甲基壳聚糖冲洗液预防大鼠术后腹膜粘连

背景：开腹手术后常造成腹膜粘连,给患者带来极大的痛苦,至今仍没有发现一种有效的药物或方法能够完全预防腹膜粘连,羧甲基壳聚糖是具有优良生物相容性和生物降解性,是理想的预防腹腔粘连的生物材料。目的：研究羧甲基壳聚糖防粘连冲洗液预防大鼠术后腹膜粘连的效果,探讨其防粘连的作用机制。 方法：取56只成年雄性Wistar大鼠建立盲肠刮伤/腹壁缺损的动物手术模型,随机分为4组,分别以生理盐水、医用透明质酸、医用几丁糖和羧甲基壳聚糖防粘连冲洗液涂布于盲肠刮伤面及腹壁缺损处。术后2,3周进行粘连分级和病理组织观察,同时测定转化生长因子β1表达、血液中白细胞数量及羟脯氨酸含量。 结果与结论：透明质酸组、几丁糖组粘连分级评分结果优于生理盐水组（P 〈0.05）,羧甲基壳聚糖组粘连分级评分结果明显优于生理盐水组（P 〈0.01）。血常规、苏木精-伊红染色和转化生长因子β1免疫组织化学染色结果显示,羧甲基壳聚糖防粘连冲洗液与医用透明质酸和医用几丁糖一样具有较好的组织相容性,可通过降低转化生长因子β1的表达、减少羟脯氨酸的合成,抑制腹腔粘连发生的程度和范围。     

Effect of glucose degradation products on the peritoneal membrane in a chronic inflammatory infusion model of peritoneal dialysis in the rat.

BACKGROUND: Long-term use of the peritoneal membrane as a dialyzing membrane is hampered by its eventual deterioration. One of the contributing factors is glucose degradation products (GDPs) in the dialysis solution. In this study, we evaluated the effect of a low GDP solution on peritoneal permeability, the structural stability of the peritoneal membrane, and vascular endothelial growth factor (VEGF) production in a chronic inflammatory infusion model of peritoneal dialysis (PD) in the rat. METHODS: Male Sprague-Dawley rats were divided into 3 groups: a conventional solution group (group C, n = 12), a test solution group (group T, n = 12), and a normal control group (group NC, n = 8). Group T rats were infused with low GDP solution (2.3% glucose solution with two compartments), and group C rats with conventional dialysis solution (2.3% glucose solution), adjusted to pH 7.0 before each exchange. Animals were infused through a permanent catheter with 25 mL of dialysis solution. In both groups, peritoneal inflammation was induced by infusing dialysis solution supplemented with lipopolysaccharide on days 8, 9, and 10 after starting dialysate infusion. Peritoneal membrane function was assessed before and 6 weeks after initiating dialysis using the 1-hour peritoneal equilibration test (PET) employing 4.25% glucose solution. Both VEGF and transforming growth factor beta1 (TGFbeta1) in the dialysate effluent were measured by ELISA. The number of vessels in the omentum was counted after staining with anti-von Willebrand factor, and the thickness of submesothelial matrix of the trichrome-stained parietal peritoneum was measured. Peritoneal tissue was analyzed for VEGF protein using immunohistochemistry. RESULTS: At the end of 6 weeks, the rate of glucose transport (D/D0, where D is glucose concentration in the dialysate and D0 is glucose concentration in the dialysis solution before it is infused into the peritoneal cavity) was higher in group T (p < 0.05) than in group C. Dialysate-to-plasma ratio (D/P) of protein was lower in group T (p < 0.05) than in group C; D/P(urea), D/P(sodium), and drain volumes did not differ significantly between groups C and T. Dialysate VEGF and TGFbeta levels were lower in group T (p < 0.05) than in group C. Immunohistochemical studies also revealed less VEGF in the peritoneal membranes of group T. There were significantly more peritoneal blood vessels in group C (p < 0.05) than in group T, but the thickness of submesothelial matrix of the parietal peritoneum was not different between the two groups. The VEGF levels in the dialysate effluent correlated positively with the number of blood vessels per field (r = 0.622, p < 0.005). CONCLUSION: Using a chronic inflammatory infusion model of PD in the rat, we show that dialysis with GDP-containing PD fluid is associated with increased VEGF production and peritoneal vascularization. Use of low GDP solutions may therefore be beneficial in maintaining the function and structure of the peritoneal membrane during long-term PD.