Background：Diffusion weighted imaging （DWI）,with the applying of intravoxel incoherent motion model,has showed promising results in obtaining additional information about microperfusion and tubular flow associated ...Background：Diffusion weighted imaging （DWI）,with the applying of intravoxel incoherent motion model,has showed promising results in obtaining additional information about microperfusion and tubular flow associated with morphologic changes in chronic kidney diseases.The study aims to evaluate the potential of T2-weighted signal intensity （SI） and DWI with mono-and bi-exponential models to reflect the serial changes on cisplatin （CP） induced rat renal fibrosis models.Methods：Magnetic resonance exams were performed prior to and 2nd day,4th day,6th day,8th day,2nd week,3rd week and 4th week after CP injection at a 3.0T with an animal coil.Besides T2-weighted images （T2WI）,DWI of 13 b values from 0 to 1500 s/mm^2 was acquired.Apparent diffusion coefficient （ADC）,fluid fraction f,pure diffusivity D and pseudodiffusivity D＊ values were calculated.The regions of interest were placed on cortex （CO）,outer stripe of the outer medulla （OM） and inner stripe of the outer medulla （OM）,parameters were measured and compared among different time points.Five rats were scarified at each time point for pathological examination.Results：OM revealed remarkable hyperintense and broadened before it became an obscure thread,while CO demonstrated moderate hyperintense and IM didn＇t show significant change on T2WI.On all three stripes,ADC values decreased firstly then kept increasing since the 4th day;f values decreased on all stripes; D values had a tendency to increase with fluctuations but the changes didn＇t achieve statistical significance; D＊ values increased at the 2nd day then tended to be steady thereafter.Pathological findings revealed tubules epitheliums swelling followed by inflammation cells infiltration,interstitial fibrosis was observed since the 2nd week.Conclusions：All of T2-weighted SI,ADC,and biexponential models parameters vary during fibrotic process; biexponential model is superior to monoexponential model in separating changes of microperfusion together with tubular flow from pure diffusion.展开更多
OBJECTIVE:To determine the mechanisms by which Kangxianling(KXL) treats renal interstitial fibrosis using a customized gene chip.METHODS:Twelve out of 18 specific pathogen-free sprague dawley(SPF SD) rats underwent a ...OBJECTIVE:To determine the mechanisms by which Kangxianling(KXL) treats renal interstitial fibrosis using a customized gene chip.METHODS:Twelve out of 18 specific pathogen-free sprague dawley(SPF SD) rats underwent a unilateral ureteral occlusion.These rats were then randomly assigned into either the model unilateral ureteral obstruction(UUO) or Kangxianling(KXL) group.The other six rats were assigned to the sham-operated group.The UUO and sham-operated groups were given normal saline via intragastric administration,whereas the KXL group was given KXL via intragastric administration.All rats were sacrificed for renal tissue collection(i.e.left nephridial tissue),and the detection of genetic changes with the customized chip.RESULTS:Compared to the sham-operated group,transforming growth factor-β1(TGF-β1),Smad2,and Smad3 genes were significantly up-regulated in the UUO group,with >1.5-fold rise(P<0.01).The Smad7 gene was significantly reduced in the UUO versus sham-operated group,with a down-regulation of >1.5-fold(P<0.01).In the KXL group,TGF-β1,Smad2,and Smad3 genes were significantly reduced compared to the UUO group,with a down-regulation of >1.5-fold(P<0.01),whereas the Smad7 gene was significantly increased compared to the UUO group,with an up-regulation of >1.5-fold(P<0.01).CONCLUSION:It was found that KXL can significantly reduce the gene levels of TGF-β1,Smad2,and Smad3.Immunohistochemistry findings also revealed significantly lower TGF-β1/Smads-mediated gene transcription activity.These findings suggest that KXL may negatively regulate the TGF-β1/Smads signal pathway to inhibit the occurrence of renal fibrosis.展开更多
基金This work was supported by grant from Chinese Nature Science Foundation （No. 81171316）.
文摘Background：Diffusion weighted imaging （DWI）,with the applying of intravoxel incoherent motion model,has showed promising results in obtaining additional information about microperfusion and tubular flow associated with morphologic changes in chronic kidney diseases.The study aims to evaluate the potential of T2-weighted signal intensity （SI） and DWI with mono-and bi-exponential models to reflect the serial changes on cisplatin （CP） induced rat renal fibrosis models.Methods：Magnetic resonance exams were performed prior to and 2nd day,4th day,6th day,8th day,2nd week,3rd week and 4th week after CP injection at a 3.0T with an animal coil.Besides T2-weighted images （T2WI）,DWI of 13 b values from 0 to 1500 s/mm^2 was acquired.Apparent diffusion coefficient （ADC）,fluid fraction f,pure diffusivity D and pseudodiffusivity D＊ values were calculated.The regions of interest were placed on cortex （CO）,outer stripe of the outer medulla （OM） and inner stripe of the outer medulla （OM）,parameters were measured and compared among different time points.Five rats were scarified at each time point for pathological examination.Results：OM revealed remarkable hyperintense and broadened before it became an obscure thread,while CO demonstrated moderate hyperintense and IM didn＇t show significant change on T2WI.On all three stripes,ADC values decreased firstly then kept increasing since the 4th day;f values decreased on all stripes; D values had a tendency to increase with fluctuations but the changes didn＇t achieve statistical significance; D＊ values increased at the 2nd day then tended to be steady thereafter.Pathological findings revealed tubules epitheliums swelling followed by inflammation cells infiltration,interstitial fibrosis was observed since the 2nd week.Conclusions：All of T2-weighted SI,ADC,and biexponential models parameters vary during fibrotic process; biexponential model is superior to monoexponential model in separating changes of microperfusion together with tubular flow from pure diffusion.
基金Supported by National Natural Science Foundation of China Grant(30873259)/(81173219)Ministry of Science and Technology in the pharmaceutical industry,scientific research and special(201007005)+7 种基金Shanghai Science and Technology Innovation Plan of Action(11DZ1973100)Shanghai Excellent academic leaders Project Grant(08XD14039)E-institute of TCM Internal Medicine of Shanghai Municipal Education Commission Grant(E03008)Innovative Research Team in Universities,Shanghai Municipal Education Commission of GrantWenzhou Science & Technology Bureau of Grant(Y20070049)Wenzhou Municipal Health Bureau of Grant(2010A012)Wenzhou Center of Traditional Chinese Medicine Laboratory GrantZhejiang Province 151 and Wenzhou Municipal 551 Talented Grant
文摘OBJECTIVE:To determine the mechanisms by which Kangxianling(KXL) treats renal interstitial fibrosis using a customized gene chip.METHODS:Twelve out of 18 specific pathogen-free sprague dawley(SPF SD) rats underwent a unilateral ureteral occlusion.These rats were then randomly assigned into either the model unilateral ureteral obstruction(UUO) or Kangxianling(KXL) group.The other six rats were assigned to the sham-operated group.The UUO and sham-operated groups were given normal saline via intragastric administration,whereas the KXL group was given KXL via intragastric administration.All rats were sacrificed for renal tissue collection(i.e.left nephridial tissue),and the detection of genetic changes with the customized chip.RESULTS:Compared to the sham-operated group,transforming growth factor-β1(TGF-β1),Smad2,and Smad3 genes were significantly up-regulated in the UUO group,with >1.5-fold rise(P<0.01).The Smad7 gene was significantly reduced in the UUO versus sham-operated group,with a down-regulation of >1.5-fold(P<0.01).In the KXL group,TGF-β1,Smad2,and Smad3 genes were significantly reduced compared to the UUO group,with a down-regulation of >1.5-fold(P<0.01),whereas the Smad7 gene was significantly increased compared to the UUO group,with an up-regulation of >1.5-fold(P<0.01).CONCLUSION:It was found that KXL can significantly reduce the gene levels of TGF-β1,Smad2,and Smad3.Immunohistochemistry findings also revealed significantly lower TGF-β1/Smads-mediated gene transcription activity.These findings suggest that KXL may negatively regulate the TGF-β1/Smads signal pathway to inhibit the occurrence of renal fibrosis.
