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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.
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Objective To research the relationship between the serum level of cystatin C (CysC),N-terminal pro brain natriuretic peptide (NT-proBNP) and the cardiovascular (CV) events in maintenance hemodialysis (MHD) patients,looking for a new and effective biological prediction method for cardiovascular disease (CVD).Methods According to the excluded criteria and included criteria,a total of 126 patients [male 67(53.2％),female 59 (46.8％)] were included in this study,screening out of 452 MHD patients from 3 blood purification centre,no secondary hyperparathyroidism,blood pressure controlled,hemoglobin standard,no lipid abnormalities,and without history of coronary heart disease,heart failure and arrhythmia.Participants adopted 3 dialysis treatment,including hemodialysis,hemoperfusion and hemodiafiltration.Every 3 months before the dialysis,the Cys-C,NT-proBNP,serum phosphorus,serum intact parathyroid hormone (iPTH),hemoglobin and electrocardiogram were detected.The heartbeat ultrasound was examined every 6 months,observed for 24 months and followed up for 3 years,recording the incidence and the inspection results.The correlation and the occurrence of CVD were analyzed by conducting a multiple factor logistic regression analysis.The forecast performance of Cys-C,NT-proBNP was evaluated by using receiver operating characteristic (ROC) curves and area under curves (AUC).Results Eighteen episodes of CV events occurred in 126 patients during the experiment and follow-up,including 8 episodes of heart failure,4 episodes of myocardial infarction,6 episodes of arrhythmia.Detection indexes had no statistically significant correlation (P ＞ 0.05),and the results of ECG and ultrasound heartbeat graph showed that no significant difference in cardiac structure and function before treatment (P ＞ 0.05).After 24 months duration,the research showed that the level of serum calcemia was lower,and the levels of phosphorus and iPTH were higher in hemodialysis group compared with that in the other 2 groups,and the differences had statistical significance (P ＜ 0.05).The median levels of Cys-C and NT-proBNP were 8.59 (9.74,7.10) mg/L and 7 739 (9 887,6 736) ng/L in the patients CV events occurred.Non conditional multivariate logistic regression analysis demonstrated that the increasing interdialytic weight,Cys-C,NT-proBNP,iPTH,dialysis hypotension were the independent risk factors of CV occurrence.AUCs to predict CVD occurrence in MHD patients was 0.64 (95％CI 0.53-0.71,P ＜ 0.05) and 0.79 (95％CI 0.72-0.89,P＜ 0.01) using Cys-C and NT-proBNP respectively.The cut-off values of serum Cys-C and NT-proBNP for CVD occurrence were 8.59 mg/L and 7 739 ng/L,with a sensitivity of 84.3％ and a specificity of 92.7％.Conclusions Cys-C,NT-proBNP can be used to predict the risk of CV events in dialysis patients.
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OBJECTIVE@#To observe the level of urinary neutrophil gelatinase-associated lipocalin (NGAL), the expression of hypoxia inducible factor-1α (HIF-1α) and NGAL in rat kidney after renal ischemia and reperfusion (I/R), before and after the treatment with Cordyceps Sinensis (C. sinensis), and to explore the mechanism of C. sinensis against I/R injury.@*METHODS@#A total of 45 healthy male Sprague-Dawley rats were randomly divided into a sham group, a renal I/R model group, and a C. sinensis group (15 in each group).The rats in the sham group and the renal I/R model group were intragastrically administered saline (2 mL/d), and rats in the treatment group were intragastricabby administered of C. sinensis [5.0 g/(kg.d)]. The rats were sacrificed at 24, 48, and 72 h, respectively after the reperfusion and urinary N-acetyl-β-D-glucosaminidase (NAG) level was measured, renal function in rats was detected, and the pathological changes were observed with HE staining. We determined the urinary NGAL levels in the rats by ELISA, the expression of HIF-1α mRNA by RT-PCR, and the expressions of HIF-1α and NGAL proteins by confocal immunofluorescence.@*RESULTS@#Compared with the sham group, the levels of BUN, SCr, levels of NAG and NGAL in urine were increased in the I/R group and the C. sinensis group, reached a peak at 24 h after the reperfusion and slowly declined at 48 and 72 h. Glomerular and tubulointerstitial areas in the sham group did not show any pathological change. Induced pathological changes included tubular cell necrosis, focal areas of proximal tubular dilation, distal tubular casts, effacement and loss of proximal tubule brush border, etc. Compared with the sham group, the expression of HIF-1α and NGAL in the kidney tissues of the I/R group and the C. sinensis group increased. C. sinensis can lower the level of NAG and NGAL in the urine and the expression of NGAL protein in the kidney tissues. It up-regulated the expression of HIF-1α mRNA and protein in the kidney tissues whilst attenuated the pathological changes.@*CONCLUSION@#Renal I/R injury in rats can lead to pathological changes in renal tubular epithelial cells and renal interstitial damage, which are consistent with the pathological features of acute kidney injury (AKI).The level of urinary NAGL increases after the I/R, and positively correlates with the level of urinary NAG and pathological changes, suggesting that urinary NGAL may serve as a urinary biomarker for specific detection of tubular injury in AKI. C. sinensis can attenuate the renal I/ R-induced AKI. Its mechanism may be associated with up-regulating the expression of HIF-1α and down-regulating the expression of NGAL in the kidney tissues.