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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 observe the effect of omapatrilat, a vasopeptidase inhibitor, on tubulointerstitial lesions in renal failure model of 5/6 nephrectomized rats and to explore a new way to prevent and cure tubulointerstitial fibrosis. Methods Rat models of 5/6 nephrectomy and renal failure were established and randomly divided into operation control group, Omap 10 mg group (omapatrilat 10 mg · kg -1 · d -1) and Omap 40 mg group (omapatrilat 40 mg · kg -1 · d-1), another set of sham operation group and normal control group. Twelve weeks later, the systolic pressure, renal function and tubulointerstitial fibrosis of rat tail artery were observed and compared (HE, Masson, PAS and PASM staining, semi-quantitative analysis). Results (1) Omapatrilat significantly reduced the blood pressure in the rats with 5/6 nephrectomy ([(153.67 ± 9.69) mmHg vs (192.00 ± 10.45) mmHg, P <0.01] (2) omapatrilat can improve renal function in 5/6 nephrectomized rats with renal failure [Scr (61.00 ± 15.50) μmol / L (97.00 ± 34.10) μmol / L, P <0.01: 19.38 ± 3.65 mmol / L BUN (30.23 ± 9.31) mmol / L, P <0.01. (3) Omapatrilat could reduce the expression of tubulointerstitial fibrosis (2.0 ± 0.63 vs 2.83 ± 0.55, P <0.05), but there was no significant difference between the two groups of 40 mg and 10 mg. Conclusion omapatrilat can significantly reduce the blood pressure in 5/6 nephrectomized rats, significantly improve renal function and delay the progression of tubulointerstitial fibrosis.