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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 protective effect of losartan and vitamin D analogue combined with paricalcitol on kidney of uremic mice. Methods: Uremic mice were divided into groups: uremia group (UC), losartan group (UL), paricalcitol group (UP), losartan + paricalcitol group (ULP). Normal rats as control group (NC). The blood pressure (BP), serum creatinine (Cr), calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 24 h urine protein and urinary podocyte (UPC) . Immunohistochemical staining of renal infiltrating macrophages (ED-1). Western blot analysis of the expression of transforming growth factor-β 1 (TGF-β 1) and hepatocyte growth factor (HGF). Results: BP in UC and UP groups were significantly higher than those in NC group and significantly higher than those in UL and ULP groups (P <0.01). Compared with NC group, Cr, P, PTH in UC group were significantly increased (P <0.01), Ca was decreased (P <0.05). Compared with UC group, the level of Cr in UL group was significantly lower, while the levels of Cr, P and PTH in UP group were significantly lower (P <0.01) and the serum calcium level was significantly higher (P <0.05). Urinary protein and UPC excretion increased 24 h in UC group compared with NC group, but could be improved by losartan and paricalcitol. The infiltration of ED-1 in renal tissue of UL, UP group was significantly lower than that in UC group, while the ULP group was significantly lower than UL and UP group. The expression of TGF-β_1 protein in UC group was significantly increased, while in UL and UP group, the expression of TGF-β_1 was significantly decreased, while the decrease in ULP group was more significant. The expression of HGF in UL, UP and ULP groups was significantly increased (P <0.01). Conclusion: Both losartan and paricalcitol have renal protective effects, and the combination of them is more obvious than single renal protection.