肾安颗粒对肾性骨病模型大鼠肾组织KLOTHO基因表达的影响

目的探讨肾性骨病模型大鼠肾组织klotho基因表达与钙磷代谢的变化及肾安颗粒干预肾性骨病作用机制。方法应用5／6肾切除加高磷饮水建立大鼠肾性骨病模型，随机分为正常对照组、假手术组、模型组、骨化三醇组、肾安2．25g／ml剂量组、肾安4．5g／ml剂量组，给予相应药物灌胃8周，给药前、后检测大鼠血尿素氮、血肌酐、血钙、血磷、碱性磷酸酶，双能x射线测骨密度，Real-time PCR、Westemblot检测klotho表达。结果肾安2．25g／ml、肾安4．5g／ml组大鼠血尿素氮、血肌酐与骨化三醇组、模型组比较明显降低。肾安2．25g／ml、肾安4．5g／ml剂量组血钙、骨密度与模型组比较明显升高，血磷、碱性磷酸酶与模型组比较明显降低。各组大鼠肾组织klotho基因、klotho蛋白表达，模型组、骨化三醇组显著低于正常组和假手术组，肾安2．25g／ml、肾安4．5g／ml组明显高于模型组。结论肾性骨病模型大鼠钙磷代谢异常与klotho基因异常表达密切相关，肾安颗粒对钙磷代谢及肾功能的影响机制可能与上调klotho基因表达有关。

Effect of Shen＇ an granule on the expression of klotho gene in renal tissues of rat renal osteodystrophy model

Objective To probe into the effects of Shen＇an granule on the expression of klotho gene in renal tissues of rat renal osteodystrophy（ROD） model. Methods The ROD model rats were randomly divided into 6 groups： normal group, sham operation group, model group, calcitriol group, high-dose Sheffan granule group （4. 5 g/ml）and low-dose Shen＇an granule group （2. 25 g/ml）. Before and after treatment for 8 weeks, BUN, SCr, serum calcium, serum phosphor, alkaline phosphatase and bone density were observed. The klotho expression in the renal tissue was detected by using real-time PCR and Western blotting. Results As compared with model group and calcitriol group, BUN and SCr levels were decreased significantly in high-dose Shen＇an granule group and low-dose Shen＇an granule group. As compared with model group, the serum calcium and bone density were significantly in- creased, and serum phosphor and alkaline phosphatase were significantly reduced in high-dose Shen＇an granule group and low-dose Shen＇an granule group. The expression levels of klotho mRNA and protein in model group were significantly lower than in normal group and sham operation group, and those in high-dose Shen＇an granule group and low-dose Shen＇an granule group were significantly higher than in model group. Conclusions Abnormal calcium-serum phosphor metabolism and abnormal expression of klotho gene are closely related in the rat ROD model. It is likely that the effect of Shen＇an granule on the calcium-serum phosphor metabolism and renal function may be contributed to the up-regulation of klotho gene expression.