黄芪对慢性肾脏病大鼠钙磷代谢及FGF23-Klotho轴的影响

The influence of Astragalus Membranaceus on Calcium and Phosphorus Metabolism and FGF23-Klotho Axis in Rats with Chronic Kidney Disease

    摘要
  • 摘要: 观察FGF23-Klotho轴在慢性肾脏病大鼠钙磷代谢中的表达变化，以及黄芪对钙磷代谢和FGF23-Klotho轴表达的影响。方法 30只SD大鼠随机分为对照组、模型组、黄芪组，适应性饲养1周后，模型组及黄芪组大鼠按照250 mg/kg给予腺嘌呤混悬液灌胃及含1.2%高磷饲料喂养4周，后改为腺嘌呤隔日灌胃2周，同时黄芪组用黄芪水煎剂12.5 g/(kg·d)灌胃治疗，对照组及模型组给予等量生理盐水灌胃。给药前每组随机抽取3只大鼠采用心脏穿刺法采血2 mL，测定血肌酐（Serum creatinine，Scr）、血尿素氮（Blood urea nitrogen，BUN）、血钙（Calcium，Ca）、血磷（Phosphorus，P），同时ELISA法测定大鼠血清甲状旁腺激素（Parathyroid hormone，PTH）、FGF23、Klotho蛋白及25(OH)D3。给药6周后，处死取肾组织，HE染色观察其变化，同时腹主动脉取血检测Scr、BUN、Ca、P，并用ELISA法测定大鼠血清PTH、FGF23、Klotho蛋白及25(OH)D3。结果 与对照组比较，模型组大鼠肾脏质量增加，Scr、BUN、Ca、P明显升高，差异有统计学意义（P<0.05~0.01），PTH升高不明显；黄芪组大鼠肾脏质量较模型组减轻，Scr、BUN、Ca、P下降，PTH升高不明显，BUN、Ca、P指标差异有统计学意义（P<0.05~0.01）。HE染色观察提示黄芪组较模型组正常肾小球数目增多，肾小管扩张程度降低，炎性细胞数量下降，腺嘌呤结晶减少。与对照组比较，模型组FGF23明显升高，Klotho蛋白及25(OH)D3明显减少；与模型组相比，黄芪组FGF23升高不明显（P<0.05），Klotho蛋白下降不明显（P<0.05）。结论 黄芪能减轻CKD病程中钙磷代谢异常，抑制FGF23过高表达，上调CKD大鼠Klotho蛋白的表达，延缓CKD大鼠肾功能进展，减轻肾脏病理损害，改善钙磷代谢。

     

    Abstract: OBJECTIVE To observe the expression change of FGF23-Klotho axis on calcium and phosphorus metabolism in rats with chronic kidney disease，and the influence of Astragalus membranaceus on them. METHODS 30 SD rats were randomly divided into three groups（control group，model group and AM group），after adaptive feeding for 1 week， 250 mg/kg adenine suspension by gastrogavage and 1.2% phosphorus content by dietary were executed to molding for 4 weeks. Then， adenine gavage was given once in 2d in the following 2 weeks; at the same time， the rats in AM group were given AM decoction 12.5 g/(kg·d) gavage and control group & model group were given normal saline equivalent. Before dosing，selected 3 rats randomly in each group to detect the level of blood urea nitrogen(BUN)，creatinine(Scr)，calcium(Ca)，phosphorus(P) via heart puncture blood.Meanwhile，the parathyroid hormone(PTH)，FGF23，Klotho and 25(OH)D3 were detected by ELISA.After 6 weeks，the histological changes in renal were observed by HE staining，the level of BUN，Scr，Ca，P in serum were detected via abdominal aortic blood.Meanwhile，PTH，FGF23，Klotho and 25(OH)D3 were detected by ELISA. RESULTS Compared with the control group，the qualities of kidney and theBUN、Scr、Ca、P levels significantly increased in model group （P<0.01，P<0.05），while the PTH level not markedly elevated. Compared with the model group， the qualities of kidney and theBUN、Scr、Ca、P levels were decreased in AM group，while the PTH level not markedly elevated，and the BUN、Ca、P levels were statistical difference（P<0.01，P<0.05）.HE staining showed that the number of normal glomerular improved， compared with the model group， the expansion degree of renal tubular decreased， the number of inflammatory cells decreased， and the crystallization of adenine decreased in the BHD group.Compared with the control group，the FGF23 level increased in model group，while the Klotho and 25(OH)D3 decreased.Compared with the model group，the FGF23 levelnot markedly elevated（P<0.05），and the Klotho not markedly declined（P<0.05）. CONCLUSION Astragalus membranaceus could alleviate the disorder of calcium and phosphorus metabolism in CKD rats，inhibit the high expression of FGF23，and up-regulate the expression of Klotho，thus improving histology of kidney， kidney function，and the balance metabolism of Ca and P in CKD rats.

     

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