Peritoneal morphologic changes in a peritoneal dialysis rat model correlate with angiopoietin/Tie-2
Peritoneal morphologic changes in a peritoneal dialysis rat model correlate with angiopoietin/Tie-2
复制标题
DOI：
10.1007/s00467-008-0944-5
复制
发表时间：
2009-01
影响因子：
3
通讯作者：
Jiangzi Yuan;W. Fang;Z. Ni;H. Dai;A. Lin;Li-ou Cao;J. Qian
中科院分区：
文献类型：
--
作者：
Jiangzi Yuan;W. Fang;Z. Ni;H. Dai;A. Lin;Li-ou Cao;J. Qian
血管生成素/Tie-2系统在血管生成的启动中起着重要作用。然而，血管生成素/Tie-2在腹膜血管生成和纤维化中的作用尚不清楚。在我们的研究中，我们观察了尿毒症腹膜透析(PD)大鼠模型的腹膜形态变化，重点研究了Angiopoietin/Tie-2与腹膜血管生成的关系。我们让尿毒症(肾大部切除)大鼠接受透析，使用标准的PD溶液，为期10天、28天或56天，并将它们与未接受透析的尿毒症大鼠和对照组大鼠进行比较。对腹膜的功能性[透析液/血浆(D/P)肌酐；超滤(UF)]和结构(腹膜下间皮下细胞外基质的血管密度和厚度)的变化进行量化。采用实时定量聚合酶链式反应(PCR)检测腹膜组织中血管生成素(Ang)-1、Ang-2、Tie-2和血管内皮生长因子(VEGF)的水平，并探讨其与血管生成的关系。未透析的尿毒症组与对照组相比，腹膜血管密度增加，UF降低，D/P肌酐升高。与尿毒症非透析组或对照组相比，PD组血管生成和纤维化进展，并伴有D/P升高，56天后PD组出现D/P升高，UF减少。与对照组相比，尿毒症非透析组Ang-2、VEGF水平显著升高，Tie-2水平显著降低。这一趋势在PD组较尿毒症非透析组或对照组更明显，但PD组之间无差异。VEGF、Ang-2与血管密度呈正相关，Tie-2与血管密度呈负相关。我们证实了尿毒症状态和PD治疗对尿毒症PD大鼠模型腹膜血管生成和纤维化的影响。尿毒症和帕金森病治疗条件下Ang-2水平升高和Tie-2水平降低与腹膜血管生成和功能恶化相关。
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.