Mechanism of Modified Liuwei Dihuangtang in Bone Protection of CKD-MBD Model Rats： An Exploration Based on Klotho-FGF23 Axis / 中国实验方剂学杂志

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（<italic>n</italic>=10），high phosphorus group（<italic>n</italic>=30），model group（<italic>n</italic>=30），modified Liuwei Dihuangtang group（<italic>n</italic>=30） ， and calcitriol group（<italic>n</italic>=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（<italic>P</italic><0.05 ，<italic>P</italic><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 （<italic>P</italic><0.05，<italic>P</italic><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.

Effect of fermented cordyceps powder and prednisone on the Notch2/Hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of both fermented Cordyceps powder (CS) and prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy (AAAN).</p><p><b>METHODS</b>Totally 50 SD rats were randomly divided into 4 groups, i.e., the normal group, the model group, the CS group, the prednisone group, and the CS plus prednisone group, 10 in each group. The AAAN rat model was induced by intragastric administration of pure aristolochic acid A at the daily dose of 100 mg/kg for 3 days. Rats in the CS group were administered with CS at the daily dose of 5.0 g/kg by gastrogavage, while those in the prednisone group were administered with prednisone at the daily dose of 0.5 mg/kg. Rats in the CS plus prednisone group were treated by CS and prednisone. All treatment lasted for 3 successive weeks. Kidney functions [urea nitrogen (BUN) and serum creatinine (SCr)] were detected. The pathological changes of kidneys were observed by Hematoxylin-Eosin staining. The apoptosis of the renal tubular epithelial cells was detected by TUNEL. The protein expressions of Notch2 and Hes-1 in the renal tissue were detected by immunohistochemical assay and Western blot.</p><p><b>RESULTS</b>Results of HE staining showed the structure in the nephridial tissue was regular in rats of the normal group. The renal tubular necrosis occurred in the rats of the model group. The pathological changes of kidneys were obviously improved in the CS group, the prednisone group, and the CS plus prednisone group. Compared with the normal group, levels of BUN and SCr, semi-quantitative score of the tubular interstitial tissue, ratio of apoptotic cells, and expressions of Notch2 and Hes-1 proteins significantly increased in the model group (P < 0.01). Compared with the model group, the aforesaid indices significantly decreased in the 3 treatment groups (P < 0.01). All indices decreased most obviously in the CS plus prednisone group (P < 0.05, P < 0. 01).</p><p><b>CONCLUSIONS</b>Notch2/hes-1 signaling activation might be associated with apoptosis of renal tubular epithelial cells. Both CS and prednisone could play a nephroprotective role for AAAN. But CS plus prednisone could achieve the best effect. Inhabiting the Notch2/hes-1 signaling activation could be its nephroprotective mechanism.</p>