RESUMO
Approximately 33.6% of nondiabetic solid organ transplant recipients who received tacrolimus developed hyperglycemia. Whether the tacrolimus-induced gut microbiota is involved in the regulation of hyperglycemia has not been reported. Hyperglycemia was observed in a tacrolimus-treated mouse model, with reduction in taxonomic abundance of butyrate-producing bacteria and decreased butyric acid concentration in the cecum. This tacrolimus-induced glucose metabolic disorder was caused by the gut microbiota, as confirmed by a broad-spectrum antibiotic model. Furthermore, oral supplementation with butyrate, whether for remedy or prevention, significantly increased the butyric acid content in the cecum and arrested hyperglycemia through the regulation of glucose-regulating hormones, including glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin, in serum. The butyrate-G-protein-coupled receptor 43-GLP-1 pathway in the intestinal crypts may be involved in the pathogenesis of normalization of hyperglycemia caused by the tacrolimus. Therefore, tacrolimus affects glucose metabolism through the butyrate-associated GLP-1 pathway in the gut, and oral supplementation with butyrate provides new insights for the prevention and treatment of tacrolimus-induced hyperglycemia in transplant recipients.
Assuntos
Microbioma Gastrointestinal , Hiperglicemia , Animais , Ácido Butírico , Peptídeo 1 Semelhante ao Glucagon , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Camundongos , Tacrolimo/efeitos adversosRESUMO
PURPOSE: Magnetic resonance defecography (MRD) was used to evaluate anatomic and functional pelvic floor disorders in women with stress urinary incontinence (SUI) before and after midurethral sling (MUS) intervention. METHOD: We performed MRD in both SUI patients and continent controls. Static MR was used to describe the anatomic abnormalities in levator ani muscle and periurethral ligaments (PUL). Dynamic MR was used to depict the function of the urethra and pelvic floor. We compared the MRD parameters between the SUI patients and continent controls before surgery. For SUI patients, dynamic MR images evaluated the functional changes of the urethra and pelvic floor after surgery. RESULTS: In SUI group, 75.8 % have PUL defects, 65.7 % discontinuity or complete loss of pubococcygeal muscle, as compared to the continent groups (p < 0.01). There was no significant difference between the perimenopausal volunteers and SUI patients in the puborectalis defection (p > 0.05). The dynamic MR showed the urethral hypermobility, functional urethra shortening, bladder neck funneling, urethra opening and cystocele were significantly associated with SUI patients (p < 0.01). Postoperative MR indicated that SUI patients after MUS had a lower risk of bladder funneling and urethral opening at the defection phase (p < 0.01), but no significant difference in urethral hypermobility or pelvic floor prolapse was seen (p>0.05). CONCLUSIONS: MRD with high-resolution and defecation phases provides a detailed anatomic and functional evaluation of the pelvic floor in female SUI before and after pelvic reconstruction.
Assuntos
Defecografia/métodos , Imageamento por Ressonância Magnética/métodos , Diafragma da Pelve/cirurgia , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias/diagnóstico por imagem , Incontinência Urinária por Estresse/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diafragma da Pelve/anatomia & histologia , Diafragma da Pelve/fisiopatologia , Estudos Prospectivos , Uretra/anatomia & histologia , Uretra/diagnóstico por imagem , Uretra/fisiopatologiaRESUMO
BACKGROUND: Chronic allograft damage (CAD) is the leading cause of long-term graft dysfunction. A noninvasive method that can diagnose CAD early and monitor its development is needed. METHODS: Kidneys from Fisher rats were transplanted into Lewis rats to establish a CAD model (n = 20). The control group underwent syngeneic kidney transplantation (n = 20). The serum creatinine of the rats was monitored. At 4, 12, and 20 weeks after modeling, a magnetic resonance imaging (MRI) examination was performed. The apparent diffusion coefficient (ADC), pseudo diffusion coefficient (D*), true diffusion coefficient (D) and perfusion fraction (f) of the two groups were analyzed. Chronic allograft damage index (CADI) scoring was used to evaluate the transplanted kidney specimens. Immunohistochemistry was used to detect the expression of fibrosis markers in the transplanted kidney tissues and to analyze their correlations with all MRI parameters. RESULTS: The transplanted kidneys in the experimental group developed CAD changes before the appearance of elevated creatinine. The MRI parameters in the experimental group [ADC (1.460 ± 0.109 VS 2.095 ± 0.319, P < 0.001), D (1.435 ± 0.102 VS 1.969 ± 0.305, P < 0.001), and f (26.532 ± 2.136 VS 32.255 ± 4.013, P < 0.001)] decreased, and D* (20.950 ± 2.273 VS 21.415 ± 1.598, P = 0.131) was not significantly different from those in the control group. ADC, D and f were negatively correlated with the CADI and the α-SMA and vimentin expression levels. CONCLUSION: Intravoxel incoherent motion (IVIM) imaging could detect CAD earlier than creatinine and reflect the degree of fibrosis in grafts quantitatively.
Assuntos
Aloenxertos/diagnóstico por imagem , Aloenxertos/transplante , Modelos Animais de Doenças , Transplante de Rim/métodos , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Aloenxertos/patologia , Animais , Sobrevivência de Enxerto/fisiologia , Rim/patologia , Transplante de Rim/efeitos adversos , Masculino , Movimento (Física) , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos LewRESUMO
Epithelialmesenchymal transition (EMT) has been demonstrated to serve a crucial role in the progression of interstitial fibrosis, which is one of the principal pathological features of chronic allograft nephropathy (CAN). However, to the best of our knowledge, the mechanisms of EMT in CAN have not been investigated. In the present study, the effect of stromal cellderived factor 1 (SDF1) and the Wnt signaling pathway on the progression of EMT following kidney transplantation was investigated. The CAN model was established using Fisher 344 and Lewis rats, treated with lowdose cyclosporine with or without AMD3100. CAN was confirmed by the pathological alterations and chronic allograft damage index scoring, and EMT was confirmed by western blotting and reverse transcriptionquantitative polymerase chain reaction. In the AMD3100 group, there were lower expression levels of αSMA and higher expression levels of Ecadherin, which indicated that CAN and EMT were ameliorated by AMD3100. The kidney tissue was analyzed using an mRNA + long noncoding (lnc)RNA microarray. A total of 506 mRNAs and 404 lncRNAs were demonstrated to be significantly differentially expressed between the two groups, which revealed the involvement of SDF1/CXC chemokine receptor 4 (CXCR4) and the Wnt pathway. SDF1 was demonstrated to induce EMT in vitro through the upregulation of αSMA, downregulation of Ecadherin and the wound healing assay, and in the rat renal tubular epithelial cells via the nuclear accumulation of ßcatenin, which were all inhibited by either AMD3100 or DKK1. CXXC finger protein 5 (CXXC5), a negative regulator of the Wnt pathway, was downregulated following treatment with SDF1, which was inhibited by AMD3100 but not by DKK1. Thus, CXXC5 may be a regulator downstream of SDF1/CXCR4 in EMT. In conclusion, SDF1/CXCR4 induces EMT of renal tubular epithelial cells with the involvement of the Wnt pathway, which may be a novel mechanism and therapeutic target in kidney allograft fibrosis of rats.