BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the commo...BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.展开更多
BACKGROUND Diabetes mellitus(DM)is a serious and growing global health burden.It is estimated that 80%of diabetic patients have micturition problems such as poor emptying,urinary incontinence,urgency,and urgency incon...BACKGROUND Diabetes mellitus(DM)is a serious and growing global health burden.It is estimated that 80%of diabetic patients have micturition problems such as poor emptying,urinary incontinence,urgency,and urgency incontinence.Patients with diabetic bladder dysfunction are often resistant to currently available therapies.It is necessary to develop new and effective treatment methods.AIM To examine the therapeutic effect of human amniotic fluid stem cells(hAFSCs)therapy on bladder dysfunction in a type 2 diabetic rat model.METHODS Sixty female Sprague-Dawley rats were divided into five groups:Group 1,normal-diet control(control);group 2,high-fat diet(HFD);group 3,HFD plus streptozotocin-induced DM(DM);group 4,DM plus insulin treatment(DM+insulin);group 5,DM plus hAFSCs injection via tail vein(DM+hAFSCs).Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure,voided volume,intercontraction interval,bladder capacity,and residual volume.Immunoreactivities and/or mRNA expression of muscarinic receptors,nerve growth factor(NGF),and sensory nerve markers in the bladder and insulin,MafA,and pancreatic-duodenal homeobox-1(PDX-1)in pancreatic beta cells were studied.RESULTS Compared with DM rats,insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume,intercontraction interval,bladder capacity,and residual volume(P<0.05).However,both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls(P>0.05).The immunoreactivities and mRNA expression of M2-and M3-muscarinic receptors(M2 and M3)were increased mainly at 4 wk(P<0.05),while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF,calcitonin gene-related peptide(CGRP),substance P,insulin,MafA,and PDX-1 were decreased in DM rats(P<0.05).However,insulin and hAFSCs treatment could help to regain the expression of M2,M3,NGF,CGRP,substance P,MafA,and PDX-1 to near the levels of controls at 4 and/or 12 wk(P>0.05).CONCLUSION Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM;however,hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.展开更多
基金the Ministry of Science and Technology Taiwan,No.MOST 109-2314-B-182A-091,No.NSTC 112-2314-B-182A-062, No.NSTC 113-2314-B-182A-125.
文摘BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.
基金Supported by the Linkou Chang Gung Memorial Hospital grants,No. CMRPG3J0951 and No. CMRPG3H1041-2Ministry of Science and Technology Taiwan grants,No. MOST 107-2314-B-182A-101 and No. MOST 109-2314-B-182A-084
文摘BACKGROUND Diabetes mellitus(DM)is a serious and growing global health burden.It is estimated that 80%of diabetic patients have micturition problems such as poor emptying,urinary incontinence,urgency,and urgency incontinence.Patients with diabetic bladder dysfunction are often resistant to currently available therapies.It is necessary to develop new and effective treatment methods.AIM To examine the therapeutic effect of human amniotic fluid stem cells(hAFSCs)therapy on bladder dysfunction in a type 2 diabetic rat model.METHODS Sixty female Sprague-Dawley rats were divided into five groups:Group 1,normal-diet control(control);group 2,high-fat diet(HFD);group 3,HFD plus streptozotocin-induced DM(DM);group 4,DM plus insulin treatment(DM+insulin);group 5,DM plus hAFSCs injection via tail vein(DM+hAFSCs).Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure,voided volume,intercontraction interval,bladder capacity,and residual volume.Immunoreactivities and/or mRNA expression of muscarinic receptors,nerve growth factor(NGF),and sensory nerve markers in the bladder and insulin,MafA,and pancreatic-duodenal homeobox-1(PDX-1)in pancreatic beta cells were studied.RESULTS Compared with DM rats,insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume,intercontraction interval,bladder capacity,and residual volume(P<0.05).However,both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls(P>0.05).The immunoreactivities and mRNA expression of M2-and M3-muscarinic receptors(M2 and M3)were increased mainly at 4 wk(P<0.05),while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF,calcitonin gene-related peptide(CGRP),substance P,insulin,MafA,and PDX-1 were decreased in DM rats(P<0.05).However,insulin and hAFSCs treatment could help to regain the expression of M2,M3,NGF,CGRP,substance P,MafA,and PDX-1 to near the levels of controls at 4 and/or 12 wk(P>0.05).CONCLUSION Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM;however,hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.
