补肾健骨方经FGF23对慢性肾脏病模型大鼠骨病调节因子的影响

Effects of Bushen Jiangu Decoction on Bone Disease Regulating Factor in Chronic Kidney Disease Model Rats through FGF23

目的:探讨补肾健骨方通过成纤维细胞生长因子23(FGF23)对腺嘌呤诱导慢性肾脏病模型大鼠骨病调节因子影响的机制研究。方法:60只成年雄性Wistar大鼠随机分为6组:正常对照组、模型组、骨化三醇组(0.045μg·kg-1)、补肾健骨方低、中、高剂量组(1.2,2.4,4.8 g·kg-1),每组10只。除正常对照组外,其余各组用含有0.75%腺嘌呤的毒性饲料连续喂养4周建立慢性肾脏病骨与矿物质代谢异常(CKD-MBD)模型。从第5周开始,补肾健骨方低、中、高剂量组和骨化三醇组灌胃给予相应药物,正常对照组和模型组灌胃给予等体积生理盐水,连续4周。给药结束后,检测血清学指标、肾脏组织病理改变、骨密度(BMD)、骨组织中FGF23、钠-磷协同转运蛋白IIa(NaPiIIa)、人细胞色素P450家族成员27B1(CYP27B1)mRNA和蛋白水平。结果:与正常对照组比较,模型组、骨化三醇组和各补肾健骨方组大鼠血清肌酐(SCr)、尿素氮(BUN)、磷(P)、甲状旁腺激素(PTH)、FGF23、NaPiIIa mRNA和蛋白水平显著升高,钙(Ca)、BMD、CYP27B1 mRNA和蛋白水平显著降低(P<0.05);与模型组比较,骨化三醇组和补肾健骨方各剂量组大鼠SCr、BUN、P、PTH、FGF23、NaPiIIa mRNA和蛋白水平显著降低,Ca、BMD、CYP27B1 mRNA和蛋白水平显著升高,且呈剂量依赖性(P<0.05);骨化三醇组和补肾健骨方中、低剂量组各指标差异有统计学意义(P<0.05)。模型组大鼠肾小管严重损伤,炎性细胞间质浸润,同时有大量肾小球硬化并伴有大量扩张的小管和间质纤维化;骨化三醇和补肾健骨方能减轻CKD-MBD模型大鼠的肾脏病理损伤。结论:补肾健骨方通过FGF23调节骨代谢和改善肾功能,对大鼠CKD-MBD具有潜在的治疗作用。

Objective:To investigate the mechanism of Bushen Jiangu decoction in the effects on bone disease regulating factor in adenine induced chronic kidney disease model rats through FGF23.Methods:Totally 60 adult male Wistar rats were randomly divided into 6 groups:the normal control group,the model group,calcitriol group(0.045μg·kg-1),Bushen Jiangu decoction low,medium and high dose groups(1.2,2.4 and 4.8 g·kg-1)with 10 rats in each group.Except the normal control group,the other groups were fed with toxic feed containing 0.75%adenine for 4 weeks to establish the model of CKD-MBD.From the 5th week,Bushen Jiangu decoction low,medium and high dose groups and calcitriol group were given the corresponding drug by gavage,and the normal control group and the model group were given an equal volume of saline for 4 weeks.After the administration,the serum indices,pathological changes of kidney tissue,bone mineral density(BMD)and the mRNA and protein levels of FGF23,NaPiIIa and CYP27B1 in bone tissue were detected.Results:Compared with those in the normal control group,the levels of SCr,BUN,P and PTH,and the mRNA and protein levels of FGF23 and NaPiIIa in the model group,calcitriol group and Bushenjiangu decoction groups were significantly increased,and the levels of Ca and BMD,and the mRNA and protein levels of CYP27B1 significantly decreased(P<0.05).Compared with those in the model group,the levels of SCr,BUN,P and PTH,and the mRNA and protein levels of FGF23 and NaPiIIa in calcitriol group and Bushenjiangu decoction groups were significantly decreased,and the levels of Ca and BMD,and the mRNA and protein levels of CYP27B1 significantly increased(P<0.05).Bushenjiangu decoction groups were in a dose-dependent manner(P<0.05).There were statistically significant differences in the indices of calcitriol group and Bushen Jiangu decoction low and medium dose groups(P<0.05).In the model group,the renal tubules were severely injured with inflammatory interstitial infiltration,and a large number of glomerular sclerosis were accompanied by a large number of dilated tubules and interstitial fibrosis.Calcitriol and Bushen Jiangu decoction could alleviate the renal pathological damage in CKD-MBD model rats.Conclusion:Bushen Jiangu decoction can regulate bone metabolism and improve renal function through FGF23,which has potential therapeutic effect on CKD-MBD in rats.