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Objective To investigate the role of autophagy in contrast-induced acute kidney injury(CI-AKI)in rats and to explore its possible mechanism.Methods SD rats were randomly divided into control group,acute kid-ney injury model group(intravenous injection of contrast medium ioversol via tail vein;model),rapamycin(RAPA)group and hydroxychloroquine(HCQ)group.Blood urea nitrogen(BUN)and serum creatinine(Scr)con-tents were measured and the potential change foun in renal pathology was detected by HE staining and microscopy.Transmission electron microscopy was used to observe auto-phagy-related changes in ultrastructure.Western blot was used to observe the expression of microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3Ⅰ,ubiquitin-binding protein p62 and Histone deacetylase 4(HDAC4).The expression of HDAC4 was also observed by RT-qPCR.Results Compared with control group,the level of BUN,Scr and HDAC4 expression in the model and HCQ group was increased(P＜0.01),the proximal tubules of the kidney were significantly damaged.In the model group,auto-phagososomes and autolysosomes increased,accompanied by an increase of LC3Ⅱ/LC3Ⅰ and a decrease in the p62 level(P＜0.05,P＜0.01);Compared with model group,there were more autophagosomes and autolysosomes were found in RAPA group(P＜0.01),accompanied by increased LC3Ⅱ/LC3Ⅰratio and decrease in the p62 and HDAC4(P＜0.05,P＜0.01).In contrast,the number of autophagy related structures decreased in HCQ group(P＜0.01),accompanied by the simultaneous increase of LC3Ⅱ/LC3Ⅰ,p62 and the increase of HDAC4(P＜0.01).Conclusions Ioversol may induce autophagy activation,while enhancing autophagy by RAPA alleviates CI-AKI induced renal dysfunction.The mechanism is potentially atributed to the regulation of HDAC4.
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Cranial magnetic resonance imaging (MRI) examinations were performed in 419 patients with type 2 diabetes mellitus (T2DM) from June to December 2016.The brain white matter lesions were defined by white matter hyperintensity (WMH) in MRI,which was detected in 380 cases (WMH group) and not detected in 39 cases (non-WMH group).The Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function.The study showed that there were significant differences in the duration of diabetes,the proportion of hypertension,total cholesterol (TC) and MoCA scores between the two groups (all P＜0.05).The age,duration of diabetes,hypertension and glyclated hemoglobin (HbA1c) were significantly correlated with white matter lesions(OR=1.157,1.116,5.184,1.128;P＜0.05);and the white matter lesions,age,and body mass index (BMI) were significantly correlated with cognitive dysfunction in diabetic patients (OR=2.137,1.175,1.247;P＜0.05).The study result indicates that control of white matter lesions may prevent and improve cognitive dysfunction in T2DM patients.
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Objective To explore the effect of simvastatin and atorvastatin on the level of p 27 protein in mesangial cells of rat under high glucose .Methods Cultured rat mesangial cells in vitro were divided into four groups :normal glucose(5 .6 mmol/L glu-cose) ,high glucose(30 mmol/L glucose) ,high glucose(30 mmol/L glucose) plus simvastatin(10 μmol/L) ,high glucose(30mmol/L glucose) plus atorvastatin(10 μmol/L) .After treatment for 24 ,48 ,72 120 hours ,the cells were collected .The protein level of p27 was detected by Western blotting and the mRNA level of p27 was detected by RT-PCR .Results Compared to the normal glucose group ,the levels of p27 protein and mRNA in the high glucose group had a significant increase(P<0 .05) .Compared to the high glucose group ,the level of p27 protein and mRNA in the high glucose plus simvastatin or atorvastatin group both had a significant decrease(P<0 .05) .Conclusion By modulating the expression of P27 in mesangial cells ,statins could become the independent lipid-decreasing drug to prevent kidney .