快胃片联合祛毒颗粒治疗慢性肾衰竭合并高磷血症大鼠钙磷代谢紊乱的效果及机制

Treatment of calcium and phosphorus metabolism disorder in rats with chronic renal failure and hyperphosphatemia with Kuaiwei Pian combined with Qudu Granule

目的观察快胃片联合祛毒颗粒治疗慢性肾衰竭(CRF)合并高磷血症大鼠钙磷代谢紊乱的效果及可能机制。方法SD大鼠随机抽取10只行假手术作为sham组,40只采用5/6肾切除加高磷饮食造模后按随机数表法分为模型组(M组)、祛毒颗粒+碳酸钙D3咀嚼片组(C组)、祛毒颗粒+低剂量快胃片组(L组)、祛毒颗粒+高剂量快胃片组(H组)。给药4周,监测大鼠血钙(Ca)、血磷(Pi)、碱性磷酸酶(ALP)、甲状旁腺激素(PTH)、尿蛋白/尿肌酐(ACR)、血肌酐(Scr)、血尿素氮(BUN)、成纤维细胞生长因子23(FGF-23)、1,25-二羟维生素D3[1,25-(OH)_(2)D_(3)]、血清koltho、肾脏病理改变和肾皮质中FGF-23的表达。结果与M组相比,给药组大鼠Pi、ALP、PTH、ACR、Scr、BUN及FGF-23下降,Ca、klotho和1,25-(OH)_(2)D_(3)上升,差异有统计学意义(P<0.05),且治疗组大鼠病理表现轻。肾皮质FGF-23表达:M组>C组≈L组>H组>sham组。结论快胃片联合祛毒颗粒可能通过FGF-23/KL轴改善CRF大鼠钙磷代谢紊乱。

Objective To observe the therapeutic effect and possible mechanism of Kuaiwei Pian combined with Qudu Granule on calcium and phosphorus metabolism disorder in rats with chronic renal failure(CRF)and hyperphosphatemia.Methods A total of 10 SD rats were randomly selected and sham-operated as the sham group.The model of 5/6 nephrectomy and high-phosphorus diet was established in 40 SD rats and they then were divided into the model group(group M),the Qudu Granule+calcium carbonate D3 chewing tablet group(group C),the Qudu Granule+low-dose Kuaiwei Pian group(group L)and the Qudu Granule+high-dose Kuaiwei Pian group(group H)according to the random number table method.After 4 weeks of dosing,rats were monitored for blood calcium(Ca),inorganic phosphate(Pi),alkaline phosphatase(ALP),parathyroid hormone(PTH),urine albumin/creatinine ratio(ACR),serum creatinine(Scr),blood urea nitrogen(BUN),fibroblast growth factor 23(FGF-23),1,25-dihydroxyvitamin D3(1,25-[OH]_(2)D_(3)),serum klotho,renal pathological change,and expression of FGF-23 in the renal cortex.Results The levels of Pi,ALP,PTH,ACR,Scr,BUN and FGF-23 of rats in the administration groups were lower than those in group M,while the levels of Ca,klotho and 1,25-(OH)_(2)D_(3) in the 3 treatment groups were higher than those in group M,with statistically significant differences(P<0.05).In addition,the pathological manifestation of rats in the 3 treatment groups was milder than that in group M.The expression of FGF-23 in renal cortex was as follows:group M>group C≈group L>group H>the sham group.Conclusion The combination of Kuaiwei Pian and Qudu Granule may improve calcium and phosphorus metabolism disorders in CRF rats through the FGF-23/KL axis.