血管内皮生长因子和内皮抑素在人腹膜组织的表达及其与腹膜毛细血管新生的关系

目的 检测血管内皮生长因子（VEGF）和血管内皮抑素（ES）在人腹膜组织表达,探讨两者与腹膜血管新生之间的关系。 方法 取健康对照者、尿毒症非透析患者以及腹透患者的腹膜标本,用反转录聚合酶链反应（RT-PCR）检测VEGF和ES mRNA的表达;组织免疫组化染色检测VEGF和ES蛋白质水平的表达;CD34染色计数腹膜组织毛细血管密度（MVD）。 结果 各组腹膜均有VEGF及ES表达;健康对照组、尿毒症非透析组、腹透组VEGF mRNA的相对表达量依次为0.47±0.01、0.62±0.02、0.74±0.02。VEGF免疫组化染色阳性区平均灰度值依次为95.673±2.01、117.126±2.07、140.184±2.25。ES免疫组化染色阳性区平均灰度值依次为94.902±2.38、113.380±2.33、145.489±3.05。尿毒症非透析组、腹透组VEGF mRNA和蛋白表达水平及ES蛋白表达水平表达均高于健康对照组,且腹透组升高更为明显,差异均具有统计学意义（均P < 0.05）。3组ES在mRNA水平表达量依次为0.42±0.02、0.43±0.03、0.43±0.02,各组表达差异无统计学意义（P > 0.05）。3组腹膜MVD依次为3.05±0.45、5.98±0.47、9.62±0.49,尿毒症非透析组、腹透组均高于健康对照组,且腹透组增高更为明显,差异均具有统计学意义（均P < 0.05）。 结论 腹膜透析患者腹膜组织VEGF mRNA和蛋白表达水平升高,ES蛋白表达水平也升高,这可能在长期透析所致腹膜组织新生毛细血管形成过程中发挥一定作用。     

重组人内皮抑素对尿毒症腹膜透析大鼠腹膜新生血管形成的影响

目的 研究重组人内皮抑素对尿毒症腹膜透析（PD）大鼠腹膜新生血管形成的影响。 方法 40只雄性SD大鼠,按随机数字表法分为正常对照组、肾衰竭非透析组、4.25%PD组、重组人内皮抑素10 mg/kg PD组、重组人内皮抑素40 mg/kg PD组,每组8只。对PD组规律PD 28 d。重组人内皮抑素干预组在行规律PD期间,隔天1次皮下注射重组人内皮抑素,至透析第28天结束。28 d后取各组大鼠新鲜腹膜组织,RT-PCR法检测腹膜组织血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF） mRNA表达;免疫组化染色检测VEGF、bFGF蛋白表达。CD34染色观察腹膜组织毛细血管密度（MVD）。 结果 各组大鼠腹膜组织均表达VEGF和bFGF,肾衰竭非透析组、4.25%PD组VEGF及bFGF mRNA、蛋白表达均显著高于正常对照组（均P < 0.05）;重组人内皮抑素10 mg/kg PD组、40 mg/kg PD组VEGF及bFGF mRNA、蛋白表达均显著低于4.25%PD组（均P < 0.05）。肾衰竭非透析组、4.25%PD组腹膜组织MVD均显著高于正常对照组（均P < 0.05）;重组人内皮抑素10 mg/kg、40 mg/kg PD组腹膜组织MVD均显著低于正常对照组（均P < 0.05）。 结论 重组人内皮抑素可以有效抑制PD大鼠腹膜新生血管的形成,下调VEGF、bFGF mRNA及蛋白表达可能是其抑制腹膜新生血管形成的机制之一。     

内皮抑素在大鼠腹膜的表达及其与腹膜血管新生的关系

目的 研究大鼠腹膜血管内皮抑素（endostatin, ES）基因及蛋白表达与腹膜血管新生的关系。 方法 32只雄性SD大鼠,按随机数字表法分为正常组、肾衰竭非透析组（非腹透组）、1.5%腹膜透析组（1.5% PD组）、4.25%腹膜透析组（4.25% PD组）,每组8只。PD组经规律PD 28 d后,取各组大鼠新鲜腹膜组织,用RT-PCR检测ES mRNA表达;用组织免疫组化染色检测ES蛋白表达;以CD34染色观察腹膜组织毛细血管密度（MVD）。 结果 各组均有ES mRNA表达,正常组为0.47±0.05;非腹透组为0.45±0.04;1.5% PD组为0.46±0.04;4.25% PD组为0.47±0.03;各组表达差异无统计学意义。正常组ES蛋白表达积分0分;非腹透组积分2分;1.5%PD组积分4分;4.25%PD组呈高表达,积分9分。正常组MVD为3.13±1.13;非腹透组为5.13±1.14;1.5%PD组为9.00±1.51;4.25%PD组为10.75±1.83;组间差异均有统计学意义（P < 0.05）。 结论 尿毒症状态和非生理性腹透液刺激可使大鼠腹膜组织ES蛋白表达升高,其在长期透析所致腹膜组织毛细血管生成增多中可能发挥一定的作用。     

Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat model of peritoneal dialysis

Abstract

Background/Aims: The present study investigated whether Rho-kinase inhibition had a therapeutic role on the pathogenesis of peritoneal fibrosis and angiogenesis. Methods: A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. Those rats were treated with Rho-kinase inhibitor, fasudil. Immunofluorescence, Western blot and RT-PCR were used to detect the expression of TGF-β1, Collagen I, αSMA and VEGF in each group. Microvessel density (MVD) was measured by immunohistochemistry. Rho-kinase activity was determined by western immunoblotting. Results: Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil. Compared with PD group, the mRNA and protein expressions of TGF-β1, αSMA and Collagen I were significantly downregulated in fasudil treatment groups in a dose-dependent manner, and the expression of VEGF and peritoneal MVD was also significantly downregulated in fasudil treatment groups in a dose-dependent manner. Conclusion: The Rho-kinase was activated in the peritoneum of the peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can remarkably decrease peritoneal fibrosis and angiogenesis.     

Effect of fluvastatin on transforming growth factor beta 1 expression in peritoneal dialysis rats model

ObjectiveTo investigate the effect of fluvastatin on TGF-β1 expression in a rat model of peritoneal dialysis(PD). MethodsA rat model of PD was built by intraperitoneal injection of 2.5% or 4.25% peritoneal dialysate. SD rats were randomly divided into 7 groups: (1) Normal control group; (2)Saline control group: saline 100 ml/kg intraperitoneal injection(IP) each day; (3) Fluvastatin treatment group: fluvastatin intragastrically administration 10 mg/kg each day; (4) 2.5% PD group: 2.5% peritoneal dialysate IP 100 ml/kg everyday; (5)4.25% PD group: 4.25% peritoneal dialysate IP 100 ml/kg everyday; (6)2.5% PD plus fluvastatin treatment group: 2.5% peritoneal dialysate IP 100 ml/kg plus fluvastatin 10 mg/kg everyday; (7)4.25% PD plus fluvastatin treatment group: 4.25% peritoneal dialysate IP 100 ml/kg plus fluvastatin 10 mg/kg everyday. The rats were sacrificed at 6 weeks and peritoneal tissues were dissected. The expressions of TGF-β1 and FN were examined by RT-PCR and immunohistochemical analysis. Masson staining was used for histological examination. ResultsMasson staining showed that the peritoneum thickened in 2.5% and 4.25% PD group than in normal control group and saline control group. The fluvastatin treatment ameliorated the thickening of peritoneum induced by PD. RT-PCR and immunohistochemical analysis showed that the mRNA and protein expression of TGF- β1 and FN increased in 2.5% and 4.25% PD group than in normal and saline control group (all P＜0.05). The fluvastatin treatment ameliorated the increased expression of TGF-β1 and FN induced by PD. There was no statistically significant difference among normal control group, saline control group and fluvastatin treatment group in both peritoneal thickness and the expression of TGF-β1 and FN. ConclusionFluvastatin can reduce the increased expressions of TGF -β1 and FN in rat peritoneum and ameliorate the thickening of peritoneum induced by PD.     

可溶性Tie2融合蛋白对尿毒症腹膜透析大鼠血管新生的影响

目的 观察可溶性Tie2融合蛋白(sTie2/Fc)对尿毒症腹膜透析大鼠腹膜血管新生的影响.方法 48只雄性SD大鼠,按随机数字表法分为以下6组:正常对照组、假手术组、尿毒症非腹透组、4.25％腹透组、sTie2/Fc 2.5 μg/kg干预组、sTie2/Fc 5.0 μg/kg干预组.腹透组按照4.25％腹透液30...     

Effects of cyclooxygenase - 2 inhibitor on peritoneal function and angiogenesis in uremic peritoneal dialysis rats

Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on angiogenesis and peritoneal function of uremic peritoneal dialysis rats. Methods Forty - eight male SD rats were selected, and they were randomly divided into five groups: normal control group(n=8), sham operation group(n=8), uremia group(5/6 nephrectomy, n=8), PD group [4.25% PD solution, 2 weeks PD model(n=8) and 4 weeks PD model(n=8)], PD + celecoxib intervention group[treated by celecoxib(20 mg/kg) via oral gavage, n=8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures, functions, peritoneal tissue capillary density (microvessel density, MVD) and COX-2, vascular endothelial growth factor (VEGF) expression level, and the impacts of celecoxib on uremic peritoneal dialysis rats peritoneal angiogenesis and peritoneal function were study. Results With the conduct of the peritoneal dialysis, peritoneal thickness increased, the inflammatory cells infiltrated, peritoneal equilibration test (PET) showed that ultrafiltration volume decreased significantly (P＜0.05), the amount of glucose transport rate rised significantly (P＜0.05), but the celecoxib could improve net ultrafiltration volume (P＜0.05), and reduce the glucose transport rate (P＜0.05). The peritoneal tissue MVD and COX - 2, VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group (all P＜0.05), were significantly lower in PD + Celecoxib intervention group than that in uremia group (P＜0.05). The correlation analysis showed that the level of COX-2 protein expression with MVD, VEGF protein expression was positively correlated (both P＜0.05), the level of VEGF protein expression and MVD was positively correlated (P＜0.05). Conclusions In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised, and the capillaries production increased in peritoneal tissue. Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats. Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats, possibly through inhibition of COX-2 expression to reduce the production of VEGF.     

Effect of the JAK2/STAT3 signaling pathway on epithelial mesenchymal transition of the peritoneum in uremic peritoneal dialysis rats

Objective To investigate whether the JAK2/STAT3 signaling pathway is involved in the epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells in uremic peritoneal dialysis (PD) rats. Methods A total of 48 male Sprague-Dawley (SD) rats were randomly separated into six groups: normal control group (NC group, n=8), sham group (n=8), uremic group (n=8), PD group (n=8), S3I-201 control group (n=8) and S3I-201 group (n=8). Uremic model generated by 5/6 nephrectomy surgery in rats was established. The rats of PD group, S3I-201 control group and S3I-201 group received daily infusion of 4.25% glucose-based peritoneal dialysate fluid (3 ml/100 g) from PD catheters for 28 days. Rats of S3I-201 group were injected with STAT3 inhibitor S3I-201 (2.5 mg/kg) solution from the catheters every other day; the same dose of the solvent of S3I-201 was simultaneously given to S3I-201 control group rats. After PD for 28 days, peritoneal function, pathologic changes, and microvessel density (MVD) were evaluated. Creatinine, urea nitrogen and interleukin-6 (IL-6) concentration in blood and dialysate, and protein and mRNA levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3), E-cadherin, alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) in peritoneum were determined. Results Uremia and peritoneal dialysate could aggravate the peritoneal function and elevate peritoneal thickness and MVD. They could also increased the concentration of IL-6 in blood and dialysate and the expression levels of α-SMA, VEGF, p-JAK2 and p-STAT3 in peritoneum, while lowering E-cadherin expression in peritoneum. These manifestations were even more remarkable in PD group compared to those in uremic group. There was no statistical difference between the S3I-201 control group and the PD group as regards all the index (all P＞0.05). Compared with the S3I-201 control group, the rats treated with S3I-201 showed better peritoneal function. S3I-201 could reduce peritoneal thickness (P＜0.05), MVD (P＜0.05), the concentration of IL-6 in blood and dialysate, the mRNA and protein expression of α-SMA, VEGF, p-JAK2 and p-STAT3 (all P＜0.05), while enhance the mRNA and protein expression of E-cadherin (all P＜0.05). Conclusions After STAT3 is inhibited, the peritoneal thickness, MVD and IL-6 concentration in PD rats are decreased, and EMT is also inhibited, while peritoneal function is improved. The JAK2/STAT3 signaling pathway may thus be involved in the process of EMT of peritoneum in uremic peritoneal dialysis rats by regulating the expression of IL-6.     

血管生成素2与腹膜透析时腹膜血管新生的关系

目的 观察血管生成素2（Angpt-2）和腹膜透析（腹透）时腹膜血管新生的关系。 方法 5/6肾切除制作尿毒症大鼠模型,成模后在腹腔内植入腹透管,根据大鼠体质量每天经腹透管注入定量腹透液（4.25%,Dineal）。按腹透时间分为未腹透组、腹透10 d组、28 d组及56 d组。假手术非尿毒症非透析大鼠为对照组。大网膜抗CD31免疫组化染色后作血管计数,观察腹膜血管新生。用实时定量PCR和Western 印迹分别检测腹膜Angpt-2和血管内皮生长因子（VEGF）表达量变化,同时检测腹膜血管数和Angpt-2、VEGF表达量的关系。 结果 未腹透组、腹透10 d、28 d及56 d组腹膜血管数显著高于对照组[（5±3）、（10±5）、（17±5）及（19±4）比（1±1） 个/HP,均P < 0.05]。腹透28 d组腹膜血管数显著高于腹透10 d组（P < 0.05）,但与56 d组差异无统计学意义。未腹透组或腹透各组腹膜Angpt-2和VEGF表达显著高于对照组（均P < 0.01）,而Angpt-2和VEGF表达量并未随透析时间延长而增加。Angpt-2和VEGF表达量和腹膜血管数呈正相关（r = 0.7756,P < 0.01;r = 0.5223,P < 0.05）。 结论 尿毒症状态和腹透促进腹膜血管新生。腹膜Angpt-2表达增加和腹膜血管新生呈正相关。Angpt-2将可能成为治疗腹膜血管新生的另一靶点     

Immunopathological changes in a uraemic rat model for peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Both the uraemic state of these patients and chronic exposure to PD fluid are associated with the development of functional and structural alterations of the peritoneal membrane. In a well-established chronic PD rat model, we compared rats with normal renal function with subtotal nephrectomized rats that developed uraemia. METHODS: Uraemic and control rats received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters during a 6 week period. Uraemic and control rats receiving no PD fluid served as controls. Parameters relevant for peritoneal defence and serosal healing responses were analyzed. RESULTS: Uraemic animals were characterized by 2-3-fold increased serum urea and creatinine levels, accompanied by a significantly reduced haematocrit. Uraemia (without PD fluid exposure) induced new blood vessels in different peritoneal tissues, accompanied by increased accumulation of advanced glycation end products (AGEs) and elevated levels of angiogenic factors such as vascular endothelial growth factor and monocyte chemoattractant protein-1 (MCP-1) in peritoneal lavage fluid. A much stronger peritoneal response was observed upon PD fluid exposure in non-uraemic rats. This included the induction of angiogenesis and fibrosis in various peritoneal tissues, accumulation of AGEs, immunological activation of the omentum, damage to the mesothelial cell layer, focal formation of granulation tissues and increased MCP-1 and hyaluronan levels in peritoneal lavage fluid. Finally, chronic PD fluid instillation in uraemic rats did not induce an additional peritoneal response compared to PD fluid exposure in non-uraemic rats, except for the degree of AGE accumulation. CONCLUSIONS: Both uraemia and PD fluid exposure result in pathological alterations of the peritoneum. However, uraemia did not induce major additive effects to PD fluid-induced injury. These results substantially contribute to the understanding of the pathobiology of the peritoneum under PD conditions.     

The abnormal expressions of tristetraprolin and vascular endothelial growth factor family which participate in ultrafiltration failure

Objective To observe the expression of tristetraprolin (TTP) and vascular endothelial growth factor (VEGF) family, to test and verify whether lymphangiogenesis was involved in the occurrence of ultrafiltration failure (UFF) as well as angiogenesis. Methods Forty male SD rats of clean grade were selected (180-200 g). These rats were divided into five groups randomly: normal group (n=8), sham operation group (n=8), uremia group (n=8), peritoneal dialysis (PD) 2-week group (n=8), PD 4-week group (n=8). The uremic rats model was established by 5/6 nephrectomy, and of which the PD rats model was established on the basis. The rats of PD2-week group and PD4-week group were given regular PD with 4.25% peritoneal dialysis fluid in dose of 3 ml/100 g body weight. PD2-week group received peritoneal dialysis for 2 weeks, PD4-week group for 4 weeks. Before the rats were sacrificed, peritoneal equilibration test (PET) was applied to calculate the mass transfer of glucose and peritoneal ultrafiltration volume. The protein expressions of VEGF, VEGF–C in each group of rats’ parietal peritoneum were detected by immunohistochemical staining. Microvessel density (MVD) and lymphatic vessel density (LVD) of peritoneal tissue were marked and quantified with anti-CD31 antibody, anti-LYVE-1 antibody. RT-PCR was applied to detect the mRNA expressions of VEGF-A, VEGF-B, VEGF-C, VEGF-D, TTP. Western blotting was used to detect the protein expression of TTP. Results (1)PET revealed that, compared with normal group, the mass transport of glucose and the peritoneal ultrafiltration volume of both PD 2-week group and PD 4-week group elevated (P＜0.05); and compared with PD 2-week group, PD 4-week group’s elevated (P＜0.05). (2) Compared with normal group, the protein expression of CD31, LYVE-1, the count of MVD and LVD were increased in uremia group and PD4-week group (P＜0.05). Those of PD4-week groups likewise were increased compared to uremia group (P＜0.05). (3) Compared with normal group, the mRNA expressions of VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D were significantly increased in uremia group (P＜0.05); Compared with uremia group, the expressions in PD4-week group were significantly increased (P＜0.05). Compared with normal group, the mRNA and protein expressions of VEGF, VEGF-C were increased in PD 2-week group (P＜0.05); Compared with PD 2-week group, the expressions were increased in PD 4-week group (P＜0.05). (4) Compared with normal group, the expressions of TTP protein was decreased in uremia group and PD 2-week group (P＜0.05). Compared with uremia and PD2-week group, the expressions of TTP protein was significantly decreased in PD4-week group (P＜0.05). Conclusions High glucose peritoneal dialysis fluid and uremic circumstance result in the expression changes of TTP and VEGF family in a PD time-dependent manner. High glucose peritoneal dialysis liquid gives rise to angiogenesis and lymphangiogenesis, both of which lead to UFF.     

音猬因子调控BMSCs表达和分泌VEGF及bFGF的实验研究

目的音猬因子(Sonic hedgehog,Shh)介导的信号参与调控血管生成的重要环节。研究不同浓度的重组Shh-N(recombinant Shh N-termitant,rShh-N)对BMSCs表达和分泌VEGF和bFGF的影响。方法取健康3日龄SD大鼠骨髓分离培养BMSCs,体外扩增至第3代,分别用含0、10、100、200 ng/mL rShh-N的L-DMEM培养BMSCs,作为A、B、C、D组。培养12、24、48、72 h后行ELISA法检测各组上清液中VEGF和bFGF的浓度,实时荧光定量PCR法检测各组VEGF和bFGF mRNA的表达水平。结果在基因表达水平上,D组各时间点的VEGF和bFGF mRNA表达量均明显高于A组(P<0.05),且在12、48 h表达量高于24、72 h(P<0.01);C组在各时间点均促进bFGF mRNA表达(P<0.05),在24～72 h促进VEGF mRNA表达(P<0.05),且在72 h时表达量均最高(P<0.01);B组在12 h抑制VEGF mRNA表达(P<0.05),48 h和72 h表现出促进作用(P<0.05),在12～48 h明显促进bFGF mRNA表达(P<0.05),且在48 h时的表达量最高(P<0.01)。在蛋白水平上,D组各时间点VEGF和bFGF分泌量均高于A组(P<0.01);C组在24～72 h VEGF和bFGF分泌量明显多于A组(P<0.05);B组在12 h和48 h抑制VEGF的分泌(P<0.05),24 h增加其分泌作用(P<0.05),而在24 h和48 h促进bFGF的分泌(P<0.05)。各组在48 h和72 h时的VEGF和bFGF分泌量明显多于12 h和24 h(P<0.05)。结论 rShh-N可促进BMSCs表达和分泌VEGF和bFGF,为进一步探讨rShh-N和MSCs联合应用于治疗缺血性相关疾病以及促进骨修复重建的可行性提供了实验依据。     

Peritoneal morphologic changes in a peritoneal dialysis rat model correlate with angiopoietin/Tie-2

The angiopoietin/Tie-2 system plays an important role in the initiation of angiogenesis. However, the role of angiopoietin/Tie-2 in peritoneal angiogenesis and fibrosis is unclear. In our study we investigated the peritoneal morphologic changes in a uremic peritoneal dialysis (PD) rat model, focusing on the relationship between angiopoietin/Tie-2 and peritoneal angiogenesis. We subjected uremic (subtotal nephrectomy) rats to dialysis, using a standard PD solution, for 10 days, 28 days, or 56 days, and compared them with uremic rats that had not undergone dialysis and control rats. Functional [dialysate-to-plasma (D/P) creatinine; ultrafiltration (UF)] and structural (vessel density and thickness of the submesothelial extracellular matrix) changes of the peritoneum were quantified. Levels of angiopoietin (Ang)-1, Ang-2, Tie-2 and vascular endothelial growth factor (VEGF) were examined in the peritoneum by real-time quantitative polymerase chain reaction (PCR) and related to angiogenesis. The uremic group that had not undergone dialysis was characterized by increased vessel density in the peritoneum compared with that of the control, which correlated with decreased UF and increased D/P creatinine. Progressive angiogenesis and fibrosis were found in the PD groups when compared with the uremic non-dialyzed or control group, accompanied by an increased D/P creatinine that occurred in the PD group after 56 days, while UF decreased. Furthermore, Ang-2 and VEGF levels increased, while Tie-2 level decreased significantly in the uremic non-dialyzed group compare with the control. This tendency was more obvious in the PD groups than in the uremic non-dialyzed or control group, but no difference was found among the PD groups. Both VEGF and Ang-2 correlated positively with vessel density, while Tie-2 correlated negatively. We confirmed angiogenesis and fibrosis changes of the peritoneum as a result of uremic status and PD therapy in the uremic PD rat model. An increased level of Ang-2 and a reduced level of Tie-2 in conditions of uremia and PD therapy correlated with peritoneal angiogenesis and functional deterioration.     

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

Rational: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. Objectives: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. Main findings: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-β were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. Principal conclusions: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-β in dialysate may be one of the possible underlying mechanisms.     

腹膜透析对人腹膜形态结构的影响

目的 探讨腹膜透析（腹透）对人腹膜，重点在间皮层形态结构的影响及其意义。方法 采用光镜，扫描电镜和透射电镜对10例正常对照者，12例尿毒症非透析患者以及10例腹透患者的腹膜活检标本进行形态学观察。结果 尿毒症非透析患者腹膜的结构与正常对照者相似，而腹透患者的腹膜形态结构随着透析时间而呈进行性改变。主要表现为间质细胞表面微绒毛减少，消失，间皮细胞从基底膜脱落直至完全消失，最后只剩下裸露的纤维结缔组织。结论 腹膜透析可引起腹膜的形态学明显改变，这可能是长期腹膜透析引起腹膜衰竭的原因之一。进一步深入研究腹膜结构与功能间关系能为人们了解长期腹透对腹膜影响的病理生理机制并进而寻找保护腹膜的手段提供理论依据。     

Peritoneal mesothelial cell biology in peritoneal dialysis

SUMMARY: Progressive peritoneal membrane hyperpermeability, ultrafiltration failure, and peritoneal fibrosis have been observed in long-term peritoneal dialysis (PD) patients, and these alterations in peritoneal structure and function may be responsible for the poor technique survival in PD. While frequent and/or severe peritonitis can result in alterations of the peritoneum, continuous exposure of the peritoneum to PD solutions may also adversely affect peritoneal structure and function. Peritoneal mesothelial cells (PMC) are directly and continuously exposed to unphysiological components of PD solution. Low pH, lactate, hyperosmolality, and glucose degradation products (GDP) reduce PMC viability and proliferation. High glucose, GDP, and advanced glycation end products (AGE) upregulate vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, plasminogen activator inhibitor (PAI)-1, and extracellular matrix protein expression by PMC, and may thus lead to peritoneal hyperpermeability, ultrafiltration failure, and peritoneal fibrosis, as observed in long-term PD. Activation of diacylglycerol (DAG)-protein kinase C (PKC) and generation of reactive oxygen species (ROS) are important upstream signalling events in high glucose-induced PMC activation. Thus, strategies to inhibit high glucose-induced PKC activation and ROS generation and the use of new PD solutions with non-glucose osmotic agents, pH neutral solutions, or solutions containing low GDP may allow better preservation of the structural and functional integrity of the peritoneal membrane during long-term PD.     

血管内皮生长因子在卵巢过度刺激综合征发病机理中的作用

目的探讨血管内皮生长因子(VEGF)在卵巢过度刺激综合征(OHSS)大鼠模型发病机理中的作用。方法OHSS组、控制性超排卵(COH)组和对照组每组6只未成年雌性大鼠。采用酶联免疫吸附试验方法测定大鼠血清和腹腔冲洗液VEGF水平;免疫组织化学方法和逆转录聚合酶链反应技术检测卵巢组织VEGF蛋白及其mRNA的表达。结果OHSS组、COH组和对照组大鼠的血清VEGF水平分别为(76.17±18.19)、(50.68±12.83)和(53.68±13.09)ng/L;其中,OHSS组的VEGF水平显著高于COH组和对照组(P<0.05),而COH组和对照组比较无显著性差异。OHSS组、COH组和对照组大鼠腹腔冲洗液VEGF水平分别为(17.12±1.71)(、9.38±5.88)和(6.68±1.86)ng/L;其中,OHSS组的VEGF水平显著高于COH组和对照组(P<0.05),而COH组和对照组比较无显著性差异(P>0.05)。OHSS组大鼠卵巢组织VEGF蛋白表达的平均灰度(97.23±7.26)显著高于对照组(78.55±8.48)和COH组(87.35±7.32)(P<0.05);COH组与对照组比较无显著性差异。OHSS组大鼠卵巢组织VEGF mRNA表达的灰度比(1.23±0.23)显著高于对照组(0.68±0.13)和COH组(0.92±0.07)(P<0.01),COH组也显著高于对照组(P<0.05)。结论VEGF在OHSS发病过程中发挥作用。