氯沙坦和帕立骨化醇联合治疗对尿毒症鼠肾脏的保护作用

Combination Therapy with Losartan and Paricaldtol Protect the Kidney in Uremic Rats

目的:观察氯沙坦和维生素D类似物——帕立骨化醇联用对尿毒症鼠肾脏的保护作用。方法:尿毒症鼠分组如下:尿毒症组(UC)、氯沙坦组(UL)、帕立骨化醇组(UP)、氯沙坦+帕立骨化醇组(ULP)。正常鼠为对照组(NC)。给药10周后检测大鼠血压(BP),血清中的肌酐(Cr)、钙(Ca)、磷(P)、甲状旁腺素(PTH),24 h尿蛋白、尿足细胞(UPC)。免疫组化染色计数肾组织浸润的巨噬细胞(ED-1)。蛋白印迹分析转化生长因子-β_1(TGF-β_1)、肝细胞生长因子(HGF)的表达。结果:UC、UP组BP较NC组显著升高,较UL、ULP组亦显著升高(P<0.01)。与NC组相比,UC组Cr、P、PTH明显升高(P<0.01),Ca降低(P<0.05)。与UC组相比,UL组Cr明显降低,UP组Cr、P、PTH也显著降低(P<0.01),且血钙水平明显升高(P<0.05)。UC组24 h尿蛋白、UPC排泄较NC组增加,但可被氯沙坦、帕立骨化醇所改善。UL、UP组肾组织ED-1阳性细胞浸润较UC组显著减少,ULP组较UL、UP组明显减少。TGF-β_1蛋白在UC组表达明显增加,UL、UP组明显减少,ULP组减少更为显著。UL、UP和ULP组HGF的表达明显增加(P<0.01)。结论:氯沙坦和帕立骨化醇均有肾保护作用,两者联用较单用肾保护作用更加明显。

Objective： To observe the beneficial effect of combination with losartan（L） and paricalcitol（P） on the kidney in ure- mic rats. Method： Uremic rats treated as follows ： Uremic （ UC）, uremic ＋ losartan （ UL）, uremic ＋ paricalcitol （ UP）, and uremic ＋ losartan ＋ paricalcitol （ULP）. A group of normal rats served as control （NC）. After the treatmemt 10 weeks, blood pressure （BP）, ser- um creatinine（ Cr）, calcium （ Ca）, phosphorus （P）, paratyyroid hormone （ PTH）, 24 h urine protein （ 24 h UP）, urinary podoctye （UPC） were measured. Immunohistochemical staining for ED-1 infiltration was counted in renal tissue. Protein expression of transfor- ming growth factor-β1 （TGF-β1 ） and hepatocyte growth factor （HGF） were determined by Western blot analysis. Result： BP was sig- nificantly elevated in the UC and UP groups compared with the NC ,UL and ULP groups （P 〈0. 01 ）. Compared with the NC greups,the increase in Cr,P,FTH （P 〈0. 01 ） and the decrease in Ca（P 〈0. 05）. Cr was significantly decreased by the use of L alone,Cr,P,PTH were significantly decreased （ P 〈 0. 01 ） and Ca increased （P 〈 0. 05） by the use of P alone compared with the UC group. The increase in the excretion of 24 h UP and UPC that were observed in the UC group were ameliorated by the use of L alone, P alone or L ＋ P. ED- 1-positive cells infiltration was significantly blunted in UL and UP groups compared with the UC group, in ULP group compared with UL and UP groups. TGF-β1 protein expression were increased in the UC group, significantly decreased in UL and UP groups,further re- duced in the ULP group. HGF protein expression were increased in the L, P, L ＋ P treated rats. Conclusion： Losartan and paricalcitol play a role in protecting the kidney. Combination therapy with Losartan and paricalcitol is more effectively than either monotherapy.