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Objective:To observe the expression levels of glial fibrillary acidic protein (GFAP), β-tubulin Ⅲ and synaptophsin, and explore the role of tripartite synapse in the mechanism of central nervous system (CNS) injury and the neuroprotective effect of chondroitin sulfate (CS).Methods:One month old clean grade, 48 female Sparague-Dawley rats and 48 male Sparague-Dawley rats, were randomly divided into 8 groups according to body weight (90 - 120 g) by random number table method, with 12 rats in each group, half male and half female. These rats were fed with water containing different concentrations of sodium fluoride (NaF) [ < 0.5 mg/L (control, CN), 10.0 mg/L (low dose fluoride, LF) and 50.0 mg/L (high dose fluoride, HF)]. Some rats were fed directly for 185 days (CN, LF and HF groups). In addition, rats of CN + normal saline (NS), LF + NS, HF + NS groups and LF + CS, HF + CS groups, were intraperitoneally injected with NS or 0.66 mg/kg CS for 5 consecutive days after 180 days of feeding. After the experiment, the pathological changes of hippocampal CA4 of brain tissue in each group were observed by hematoxylin eosin staining under light microscope, and the expression and distribution of GFAP, β-tubulin Ⅲ and synaptophsin in hippocampal CA4 of rats were detected by immunohistochemistry, the expression of GFAP, β-tubulin Ⅲ and synaptophsin at protein level in hippocampus of rats were detected by Western blotting.Results:Under light microscope, eosinophilic change, loss and irregular arrangement of neuron in the hippocampal CA4 were observed in LF, HF, LF + NS and HF + NS groups. The morphology of LF + CS and HF + CS groups was not significantly changed compared with CN group, but was significant changed compared with LF, HF, LF + NS and HF + NS groups. Immunohistochemical results showed that the rates of positive area of GFAP, β-tubulin Ⅲ and synaptophsin in female and male rats in LF and HF groups were significantly decreased than those in CN group ( P < 0.05); the positive area rates of female and male rats in LF + CS and HF + CS groups were higher than those in LF and HF groups, respectively ( P < 0.05). Western blotting results showed that the proten expression levels of GFAP, β-tubulin Ⅲ and synaptophsin of female and male rats in LF and HF groups (LF group: 0.90 ± 0.09, 0.82 ± 0.08, 1.43 ± 0.14, 0.92 ± 0.02, 1.21 ± 0.15, 0.87 ± 0.02, HF group: 0.58 ± 0.14, 0.73 ± 0.03, 0.63 ± 0.06, 0.67 ± 0.03, 0.87 ± 0.04, 0.70 ± 0.05) were lower than those in CN group (1.24 ± 0.08, 1.09 ± 0.10, 2.64 ± 0.30, 1.54 ± 0.09, 1.72 ± 0.10, 1.13 ± 0.06, P < 0.05). Conclusions:The tripartite synapse and extracellular matrix may take part in pathogenesis of the damages of CNS results from chronic fluorosis; CS may reduce the injury to a certain extent.
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Objective To investigate the risk factors of clinically diagnosed acute kidney injury (AKI) patients progressing to acute kidney disease (AKD). Methods The clinical data of AKI patients admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2018 were retrospectively analyzed. According to the outcome of the patients, AKI patients were divided into non - acute kidney disease (NAKD) group and AKD group. Clinical characteristics and laboratory data of two groups were compared. The risk factors of AKD in patients with AKI were analyzed by logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors. Results A total of 254 patients with AKI were enrolled, and 186 patients developed AKD with an incidence of 73.2％. Theincidences of AKD in stage 1, stage 2 and stage 3 of AKI were 20.0％, 46.7％and 83.5％respectively. Multivariate logistic regression analysis showed increased peak serum creatinine (within 7 days after AKI diagnosis) (OR=2.561, 95％ CI 1.584-4.140, P<0.001), proteinuria (OR=2.952, 95％ CI 1.162-7.500, P=0.023) and increased intact parathyroid hormone (OR=1.757, 95％CI 1.104-2.797, P=0.017) were independent risk factors for progression to AKD in patients with AKI. The ROC showed that increased peak serum creatinine (within 7 days after AKI diagnosis) was an important predictor of AKD in patients with AKI (AUC=0.798, P<0.001). Conclusion Increased peak serum creatinine (within 7 days after AKI diagnosis), proteinuria and increased intact parathyroid hormone are independent risk factors for progression to AKD in patients with AKI, providing new evidences and ideas for clinical preventions and treatments of AKD.
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Objective To study the mechanism of central nervous system (CNS) injury in chronic fluorosis and the neuroprotective effect of chondroitin sulfate (CS).Methods Forty-eight female Sprague-Dawley rats weighting 90-120 g were divided into 8 groups according to body weight by random number table,6 rats in each group:control group,drinking tap water freely;low dose and high dose fluoride groups,freely drinking tap water with fluoride content of 10 and 50 mg/L,respectively;control + normal saline (NS),low dose fluoride + NS,and high dose fluoride + NS groups,each group was fed for 180 d,and treated with intraperitoneal injection of 0.66 mg/kg NS for 5 d (once a day);low dose fluoride + CS and high dose fluoride + CS groups,each group was fed for 180 d,0.66 mg/kg CS was injected intraperitoneally for 5 d (once a day).All groups were fed standard nutritive animal feed for 185 d and dissected for brain tissue.The pathologic change was observed after hematoxylin-eosin (HE)staining;the expression levels of phosphorylated extracellular signal-regulated protein kinase 1/2 (phospho-Erk1/2)and glutamate receptors 1,2 (GluR1,GluR2) in the brain cortex were detected by immunohistochemistry;the protein levels of Erk1/2,phospho-Erk1/2,GluR1,and GluR2 in the brain cortex were detected by Western blotting.Results Brain cortex of all rats in the fluoride groups showed eosinophilic degeneration,loss and disordered arrangement of neurons,and the brain morphological changes in each fluoride + CS groups were significantly improved compared with those in the fluoride groups.Immunohistochemistry results showed that compared with the control group [(0.44 ± 0.09)％,(1.49 ± 0.05)％,(2.51 ± 0.54)％],the expression levels of phospho-Erk1/2 [(1.47 ±0.09)％,(1.03 ± 0.05)％],and GluR2 [(2.37 ± 0.06)％,(3.38 ± 0.12)％] in the low dose and high dose fluoride groups were increased,and the expression levels of GluR1 [(1.49 ± 0.02)％,(0.99 ± 0.19)％] were decreased (P ＜ 0.05).Western blotting results showed that compared with the control group (1.00 ± 0.12,1.76 ± 0.33),the protein levels of Erk1/2 (3.10 ± 0.76,1.99 ± 0.01) and phospho-Erk1/2 (3.27 ± 0.25,2.67 ± 0.05) in low dose and high dose fluoride groups were significantly increased (P ＜ 0.05);compared with low dose fluoride group,the protein levels of Erk1/2,and phospho-Erk1/2 (1.30 ± 0.31,2.20 ± 0.34) in low dose fluoride + CS group decreased significantly (P ＜0.05).Compared with control group (1.86 ± 0.47,1.17 ± 0.27),the protein levels of GluR1 (1.09 ± 0.26,0.61 ± 0.14) in low dose and high dose fluoride groups decreased significantly,while the protein level of GluR2 (1.99 ± 0.42,3.38 ±0.27) increased significantly (P ＜ 0.05);compared with low dose and high dose fluoride groups,the protein levels of GluR2 in low dose fluoride + CS and high dose fluoride + CS groups (1.53 ± 0.41,2.65 ± 0.32) decreased significantly (P ＜ 0.05).The protein level of phospho-Erk1/2 was negatively correlated with GluR1 protein level (r =-0.975,-0.991,P ＜ 0.05) in low dose and high dose fluoride groups,and it was positively correlated with the protein level of GluR2 (r =0.986,0.993,P ＜ 0.05).Conclusion The CNS injury caused by chronic fluorosis may be related to GluR1 and GluR2 activated Erk1/2 signaling pathway,and CS has certain protection to the injury.
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Objective@#To investigate the risk factors of clinically diagnosed acute kidney injury (AKI) patients progressing to acute kidney disease (AKD).@*Methods@#The clinical data of AKI patients admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2018 were retrospectively analyzed. According to the outcome of the patients, AKI patients were divided into non-acute kidney disease (NAKD) group and AKD group. Clinical characteristics and laboratory data of two groups were compared. The risk factors of AKD in patients with AKI were analyzed by logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors.@*Results@#A total of 254 patients with AKI were enrolled, and 186 patients developed AKD with an incidence of 73.2%. The incidences of AKD in stage 1, stage 2 and stage 3 of AKI were 20.0%, 46.7% and 83.5% respectively. Multivariate logistic regression analysis showed increased peak serum creatinine (within 7 days after AKI diagnosis) (OR=2.561, 95% CI 1.584-4.140, P<0.001), proteinuria (OR=2.952, 95% CI 1.162-7.500, P=0.023) and increased intact parathyroid hormone (OR=1.757, 95%CI 1.104-2.797, P=0.017) were independent risk factors for progression to AKD in patients with AKI. The ROC showed that increased peak serum creatinine (within 7 days after AKI diagnosis) was an important predictor of AKD in patients with AKI (AUC=0.798, P<0.001).@*Conclusion@#Increased peak serum creatinine (within 7 days after AKI diagnosis), proteinuria and increased intact parathyroid hormone are independent risk factors for progression to AKD in patients with AKI, providing new evidences and ideas for clinical preventions and treatments of AKD.