摘要
目的 观察血管肽酶抑制剂omapatrilat对5／6肾切除大鼠肾衰模型肾小管间质 病变的影响,探索防治肾小管间质纤维化的新途径。方法建立5／6肾切除肾衰大鼠模型,随 机分成手术对照组、Omap 10 mg组(omapatrilat 10 mg·kg-1·d-1)和Omap 40 mg组(omapatrilat 40 mg·kg-1·d-1),另设假手术组和正常对照组。12周后观察比较各组间大鼠尾部动脉收缩压、 肾功能、肾小管间质纤维化水平(HE、Masson、PAS和PASM染色,半定量分析)。结果(1)omapatrilat 能明显降低5／6肾切除肾衰竭大鼠血压水平[(153.67±9.69)mmHg比(192.00±10.45)mmHg, P<0.01],且Omap 40 mg组降压效果明显优于Omap 10 mg组[(142.50±11.14)mmHg比 (153.67+9.69)mmHg,P<0.05];(2)omapatrilat能改善5／6肾切除肾衰竭大鼠肾功能[Scr(61.00±15.50) μmol／L比(97.00±34.10)μmol／L,P<0.01:BUN(19.38±3.65)mmol／L比(30.23±9.31)mmol／L, P<0.01 1:(3)omapatrilat可减轻肾小管间质纤维化程度(2.0±0.63比2.83±0.55,P<0.05),但 40 mg和10 mg两剂量组差异无统计学意义。结论 omapatrilat能明显降低5／6肾切除大鼠血 压水平.显著改善其肾功能及延缓肾小管间质纤维化进展。
Objective To investigate the effect of vasopeptidase inhibitors (VPi) omapatrilat on renal tubulointerstitial fibrosis of 5/6 subtotal nephrectomized rats and to explore new prevention and treatment of renal lubulointerstitial fibrosis.Methods The renal subtotal ablation model was established by surgical 5/6 renal resection in male SD rats.Five animal groups included(1)STN group (subtotal nephreclomy); (2)Omap 10 mg group (10 mg·kg-1·d-1); (3)Omap 40 mg group (40 mg·kg-1·d-1) ; (4)Sham group and (5)Nornial control. Systolic arterial BP and renal function were measured periodically.Animals were sacrificed at the end of the 12th week after operation. Tubulointerstitial injury was scored semiquantitatively by morphological analysis (HE, Masson, PAS and PASM stain). Results Significant tubulointerstitial injury was noted in the STN group compared with normal group and sham group (P<0.01). Blood pressure, tubulointerstitial injury and renal function were improved in omapatrilat treated groups as compared to STN group. [BP (153.67±9.69) mmHg vs (192.00±10.45)mmHg,P<0.01;tubulointerstitial injury 2.00±0.63 vs 2.83±0.55 ,P<0.05 and Scr (61.00±15.52)μmol/L vs (97.00±34.10)μmol/L, P<0.01]. Conclusion Omapatrilat can markedly decrease blood pressure and obviously ameliorate tubulointerstitial fibrosis and renal function.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2005年第4期204-206,共3页
Chinese Journal of Nephrology
基金
国家自然科学基金(30270613)上海市科学技术委员会重大项目(03JC14084)
