Page 57 - 《中国药房》2021年第6期

Effects of Modified Liuwei Dihuang Decoction on Kidney/Bone Injury of CKD-MBD Model Rats
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GUO Huahui ，LIANG Qunqing ，LI Hesheng ，YANG Yilong ，HUANG Jiasheng ，CHEN Penghui ，LAN
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Congying ，HUANG Renfa [1. Graduate School，Guangxi University of TCM，Nanning 530200，China；2. Health
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Examination Center，Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine，Nanning 530011，
China；3. Dept. of Nephrology，Shenzhen Hospital （Futian），Guangzhou University of TCM，Guangdong
Shenzhen 518034，China]
ABSTRACT OBJECTIVE：To study the effects of Modified liuwei dihuang decoction on kidney/bone injury of chronic kidney
disease-mineral and bone disorder（CKD-MBD）model rats. METHODS：The male SD rats were randomly divided into normal
group（n＝10），high phosphorus group（n＝30），model group（n＝30），calcitriol group（positive control，0.09 μg/kg，n＝30），
Modified liuwei dihuang decoction group（10 g/kg by crude drug，n＝30）. CKD-MBD model was established by high phosphorus
and adenine diet for 6 weeks. After modeling，normal group and model group were given normal diet/high phosphorus diet and
intragastric administration of water. Administration groups were fed with normal diet and given corresponding solution
intragastrically（water as solvent），0.1 mL/kg，once a day，for consecutive 6 weeks. Blood sample of rats in the normal group
were collected，and they were sacrificed after the last administration. Blood sample of 10 rats in each other group were collected，
and they were sacrificed at 2，4 and 6 weeks after administration. The contents of blood urea nitrogen（BUN），serum creatinine
（Scr），calcium，phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum were detected in each group. The bone mineral
density （BMD） of femoral was measured，the morphological changes of renal tissue and bone tissue were observed，and the
percentage of renal tubular injury and the score of renal interstitial fibrosis were calculated. RESULTS：Compared with normal
group，above indexes in high phosphorus group had no significant change at different time points （P＞0.05）. There was no
abnormal change in renal/bone tissue. Compared with high phosphorus group at the same time point，the contents of BUN，Scr，
phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum，the percentage of renal tubular injury and the score of renal
interstitial fibrosis in the model group were significantly increased，while the contents of calcium in serum and the BMD of femoral
were significantly decreased（P＜0.05 or P＜0.01）. The renal tissue showed diffuse fibrosis. The width of trabecular bone was
increased and the number of osteoblasts was decreased. Compared with the model group at the same time point，the contents of
BUN （except for Modified liuwei dihuang decoction group after 2 weeks of administration），Scr，serum phosphorus，iPTH，
FGF-23，RANKL and osteocalcin，the percentage of renal tubular injury and the score of renal interstitial fibrosis in Modified
liuwei dihuang decoction group and calcitriol group were decreased significantly at each time point；serum calcium content and
BMD（except for 2 weeks of administration）were significantly increased（P＜0.05 or P＜0.01），and the pathological changes of
renal/bone tissue were significantly improved；there was no statistical significance in above indexes between Modified liuwei
dihuang decoction group and calcitriol group（P＞0.05）. CONCLUSIONS：Modified liuwei dihuang decoction can improve kidney/
bone injury of CKD-MBD model rats，and improve BMD and regulate disorder of calcium and phosphorus metabolism.
KEYWORDS Modified liuwei dihuang decoction；Chronic kidney disease-mineral and bone disorder；Renal tissue；Bone tissue；
Injury；Rats

慢性肾脏病矿物质和骨异常（Chronic kidney dis- 异常，从而引发骨质疏松等疾病 。近期研究发现，骨细
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ease-mineral and bone disorder，CKD-MBD），旧称肾性骨 胞可通过分泌成纤维生长因子 23（FGF-23）、骨硬化蛋
病，是慢性肾脏病（Chronic kidney disease，CKD）患者在 白、Wnt 经典信号通路抑制因子 Dickkopf 1（Dkk1）等来
疾病进展过程中常见的并发症，主要的临床表现为低钙 影响成骨细胞和破骨细胞的功能，在骨代谢和骨发育中
高磷的钙磷代谢紊乱、继发性甲状旁腺功能亢进、骨代 发挥重要作用，其中 FGF-23 水平在 CKD 早期即可见明
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谢异常和转移性钙化等，此症不仅会引起骨质疏松、骨 显升高，被认为是CKD早期诊断的标志物 。
痛、骨折和骨骼畸形等，还会导致血管及其他软组织发 六味地黄汤出自于《景岳全书》卷五十三，即《小儿
生转移性钙化并诱发心血管事件，严重影响 CKD 患者 药证直诀》，具有滋阴补肾之功效，主治肝肾阴虚、真阴
的生存质量及长期预后 。众所周知，骨转换异常是 亏损、精血枯竭等 。加味六味地黄汤是在六味地黄汤
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CKD-MBD 的重要病理特征 ，而骨转换主要涉及骨吸 的基础上，加入大黄、桂枝、丹参、黄芪、淫羊藿等药制
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收和骨形成两方面。其中，破骨细胞负责吸收老化的旧 得；取大黄祛瘀攻逐解毒，桂枝温阳利水，丹参活血祛
骨，成骨细胞则生成等量新骨，破骨细胞的标志物有核 瘀，黄芪健脾益气利水，淫羊藿补肾阳、强筋骨等功效，
因子κB 受体活化因子配体（RANKL），成骨细胞的标志 全方具有补肾利水、祛瘀排毒及强筋骨之功效。本课题
物有骨钙素；若骨吸收和骨形成不平衡则可导致患者骨 组前期研究显示，加味六味地黄汤可通过抑制肾组织中

中国药房 2021年第32卷第6期 China Pharmacy 2021 Vol. 32 No. 6 ·691 ·