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目的:观察维生素D受体激动药帕立骨化醇对尿毒症大鼠肾脏的保护作用。方法:雄性SD大鼠切除右肾并结扎左肾动脉前支诱导尿毒症模型。将20只尿毒症鼠随机分为尿毒症组(UC组)、UC+帕立骨化醇治疗组(UA组)。另设正常SD大鼠为对照组(NC组)。第10周检测大鼠血清Ca、P、1,25(OH)_2D_3、成纤维细胞生长因子23(FGF23)、甲状旁腺素(PTH)、血管紧张素Ⅱ(AngⅡ)、血肌酐(Scr)、白蛋白(Alb)、24 h尿蛋白(24 h UP)。RT-PCR检测肾小球血管紧张素原(Ang)、血管紧张素转化酶(ACE)、nephrin、synaptopodin的表达胞核WT-l阳性细胞计数测定每个肾小球足细胞数量。结果:UC组P、FGF23、PTH、AngⅡ、Scr、Alb、24 h UP较NC组显著升高(P<0.01),Ca、l,25(OH)_2D_3、Alb降低(P<0.05或0.01)。UC组Ang、ACE mRNA的表达较NC组显著增加(P<0.01);nephrin、synaptopodin mRNA的表达较NC组显著降低(P<0.叭);肾小球足细胞数目减少。帕立骨化醇改善尿毒症鼠的矿物质代谢,下调AngⅡ水平,减少尿蛋白的排泄;抑制肾小球Ang、ACE mRNA的表达,恢复nephrin、synaptopodin的表达,并维持肾小球足细胞数量。结论:帕立骨化醇可抑制尿毒症鼠肾小球血管紧张素活性,减轻足细胞损伤和脱落。
Objective: To observe the protective effect of paricalcitol, a vitamin D receptor agonist, on the kidney of uremic rats. Methods: Male SD rats were excised from the right kidney and ligation of the anterior branch of the left renal artery to induce uremia. 20 uremic mice were randomly divided into uremia group (UC group) and UC + paricalcitol group (UA group). Another normal SD rats as control group (NC group). At week 10, serum Ca, P, 1,25 (OH) _2D_3, FGF23, PTH, Scr, , Albumin (Alb), 24 h urine protein (24 h UP). The expression of glomerular angiotensinogen (Ang), angiotensin converting enzyme (ACE), nephrin and synaptopodin was measured by RT-PCR. The number of nucleated WT-1 positive cells was counted to determine the number of each glomerular podocyte. Results: The levels of P, FGF23, PTH, AngⅡ, Scr, Alb and 24 h UP in UC group were significantly higher than those in NC group (P <0.01) . The expression of Ang and ACE mRNA in UC group was significantly higher than that in NC group (P <0.01). The expression of nephrin and synaptopodin mRNA in NC group was significantly lower than that in NC group (P <0.01). The number of glomerular podocyte was decreased. Paricalcitol can improve the mineral metabolism, reduce the level of AngⅡ and decrease the excretion of urinary protein in uremic mice, inhibit the expression of Ang, ACE mRNA, restore the expression of nephrin and synaptopodin, and maintain the number of glomerular podocytes . Conclusion: Paricalcitol can inhibit glomerular angiotensin-converting enzyme activity in uremic mice and reduce podocyte injury and shedding.