Mechanism of Modified Liuwei Dihuangtang in Bone Protection of CKD-MBD Model Rats: An Exploration Based on Klotho-FGF23 Axis
10.13422/j.cnki.syfjx.20212496
- VernacularTitle:基于Klotho-FGF23轴探讨加味六味地黄汤对CKD-MBD模型大鼠骨保护作用的机制
- Author:
Hua-hui GUO
1
;
Mei-dan LI
2
;
Ren-fa HUANG
1
;
Qun-qing LIANG
3
;
He-sheng LI
1
;
Xue-pin LIU
1
;
Ruo-lin WANG
1
;
Si-heng SHEN
1
Author Information
1. Shenzhen Hospital of Guangzhou University of Chinese Medicine(Futian),Shenzhen 518034,China
2. Zhaoqing Hospital of Traditional Chinese Medicine,Zhaoqing 525000,China
3. Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,China
- Publication Type:Research Article
- Keywords:
modified Liuwei Dihuangtang;
renal osteopathy;
fibroblast growth factor 23 (FGF23);
Klotho protein
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(24):61-70
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effects of modified Liuwei Dihuangtang on serum fibroblast growth factor 23 (FGF23), full-length intact parathyroid hormone (iPTH), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels and Klotho and FGF23 protein expression in renal and bone tissues of rats exposed to high phosphorus combined with adenine, so as to explore the mechanism of modified Liuwei Dihuangtang against renal osteopathy. Method:One hundred and thirty healthy adult SD rats were randomly divided into five groups, namely normal group(n=10),high phosphorus group(n=30),model group(n=30),modified Liuwei Dihuangtang group(n=30) , and calcitriol group(n=30),and rats in each group were further classified based on three time points, namely 8,10, and 12 weeks. Rats in the normal group were fed with normal diet, the ones in the high phosphorus group with high phosphorus diet, and those in the other groups with adenine and high phosphorus diet for inducing renal osteopathy. Rats in the normal group,high phosphorus group, and model group were intragastrically administered with distilled water (10 mL·kg-1·d-1),the ones in the modified Liuwei Dihuangtang group with modified Liuwei Dihuangtang (2.556 g·kg-1·d-1) , and those in the calcitriol group with calcitriol (0.09 μg·kg-1·d-1). Result:Compared with the normal group and high phosphorus group at the weeks of 8,10 and 12,the model group displayed significantly elevated blood urea nitrogen(BUN),serum creatinine(SCr),serum phosphorus,iPTH,FGF23,renal interstitial fibrosis score, and FGF23 expression in renal and bone tissues, but lowered serum calcium and 1,25(OH)2D3 and Klotho protein expression in renal and bone tissues(P<0.05 ,P<0.01). Compared with the model group at the weeks of 8,10 and 12, the modified Liuwei Dihuangtang and calcitriol both significantly decreased the serum BUN,SCr,serum phosphorus,iPTH, FGF23, tubulointerstitial semi-quantitative score, and FGF23 expression in renal and bone tissues, while increased the serum calcium,1,25(OH)2D3, and Klotho protein expression in renal and bone tissues (P<0.05,P<0.01). There was no significant difference in the above-mentioned indexes between the modified Liuwei Dihuangtang group and the calcitriol group at the same time point. Conclusion:Klotho-FGF23 axis is probably involved in renal osteopathy. The modified Liuwei Dihuangtang effectively improves renal function,alleviates pathological changes in renal and bone tissues,and regulates calcium and phosphorus metabolism to protect the bone, which is related to its regulation of Klotho-FGF23 axis.