摘要
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10d组、28d组及56d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10d、28d及56d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〈0.051。腹透28d组腹膜血管数显著高于腹透10d组(P〈0.05),但与56d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。
Objective To investigate the association between angiopoietin-2 (Angpt-2) and peritoneal angiogenesis in a uremic peritoneal dialysis (PD) rat model. Methods Uremic (subtotal nephrectomy) rats were established and divided into non-PD, 10 d-PD, 28 d-PD and 56 d-PD groups. Standard PD solution was applied in the study. Rats undergone sham operation without PD were used as control group. Vessel density of the peritoneum was detected and quantified with anti-CD31 immunohistochemical staining. Expressive levels of Angpt-2 and vascular endothelial growth factor (VEGF) were examined in the peritoneum by real-time PCR and Western blotting. Results The non-PD group was characterized by increased vessel density in the peritoneum compared with that of the control group [(5+3)/HP vs (1+1)/HP]. Progressive angiogenesis was found in 10 d-PD, 28 d-PD and 56 d-PD groups [( 10+5 )/HP, (17+5)/HP, (19+ 4)/HP]. Furthermore, expressive levels of Angpt-2 and VEGF increased significantly in the non-PD group compared with the control (P〈0.01), and such expressions were significantly higher in the PD groups as compared to non-PD group (P〈0.01), but no difference was found among the PD groups. Both VEGF and Angpt-2 levels were positively correlated with vessel density(r=0.7756, P〈 0.01; r=0.5223, P〈0.05). Conclusions Uremia and PD promote peritoneal angiogenesis in rats. Increased expression level of Angpt-2 in peritoneum is positively correlated with peritoneal angiogenesis. Angpt-2 may be a new therapeutic target of peritoneal angiogenesis.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2009年第6期415-419,共5页
Chinese Journal of Nephrology
基金
上海市科委课题基金(044119620,177QA14040,08dz1900501)
关键词
腹膜透析
新生血管化
病理性
血管生成素2
血管内皮生长因子
Peritoneal dialysis
Neovascularization, pathologic
Angiopoietin-2
Vascular endothelial growth factor