In this review,we focused on two molecules,connexin and sodium-glucose cotransporter,which can link to diabetic hyperfiltration.In diabetic kidney,the activation of renin-angiotensin system occurs simultaneously with ...In this review,we focused on two molecules,connexin and sodium-glucose cotransporter,which can link to diabetic hyperfiltration.In diabetic kidney,the activation of renin-angiotensin system occurs simultaneously with glomerular hyperfiltration.The latter largely dependson pathophysiological afferent arteriolar dilation in the presence of high angiotensin Ⅱ.As a mechanistic basis for the above,tubular hypothesis has been proposed for type 1 diabetic patients as well as experimental models.Although tubular hypothesis has not been well evaluated in type 2 diabetes,clinical observations support that tubular hypothesis is true also in type 2 diabetes.Recent results on tubular hypothesis along with connexin abnormality in type 2 diabetes were revisited.In addition,the importance of sodium-glucose cotransporter in diabetic hyperfiltration is discussed.The link between salt paradox and the activation of reninangiotensin system will be also reviewed.展开更多
Objective：To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods：A mathematical model is developed based on response （MR） Hagan-Poiseuille law and ...Objective：To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods：A mathematical model is developed based on response （MR） Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic tubuloglomerular feedback （TGF） and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results：The results predict the dynamics of renal autoregulation on its blood pressure and flow, and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion ：The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.展开更多
目的:观察补脾益肾方对糖尿病肾病大鼠疗效及管球反馈机制的影响。方法:100只雄性SD大鼠随机取25只作为正常组,余75只应用高脂高糖饮食联合小剂量链脲佐菌素(STZ)腹腔注射建立糖尿病大鼠模型,将成模大鼠随机均分为模型组、补脾益肾组、...目的:观察补脾益肾方对糖尿病肾病大鼠疗效及管球反馈机制的影响。方法:100只雄性SD大鼠随机取25只作为正常组,余75只应用高脂高糖饮食联合小剂量链脲佐菌素(STZ)腹腔注射建立糖尿病大鼠模型,将成模大鼠随机均分为模型组、补脾益肾组、氯沙坦组、补脾益肾组予补脾益肾方23.4 g·kg^(-1)灌胃,氯沙坦组予氯沙坦片9 mg·kg^(-1)灌胃,正常组和模型组予以等体积蒸馏水灌胃,持续治疗11周,每2周测1次随机血糖,第11周结束后取材进行指标检测,各组大鼠放入代谢笼,记录24 h尿量。酶联免疫吸附测定法(ELISA)检测24 h尿微量白蛋白定量(24 h UAER)、肾小管损伤相关蛋白和尿肌酐,取血检测血肌酐、尿素氮;行苏木素-伊红(HE)染色、糖原(PAS)染色、马松(Masson)染色观察大鼠肾脏病理变化;免疫组化法观察大鼠肾钠-葡萄糖共转运蛋白1(SGLT1),钠-葡萄糖共转运蛋白2(SGLT2)、钠-钾-氯协同转运蛋白2(NKCC2)、缝隙连接蛋白40(CX40)表达,免疫荧光观察腺苷Ⅰ型受体(A1AR)在肾脏定位;蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)检测肾脏组织SGLT1、SGLT2、NKCC2、CX40、A1AR的表达。结果:与正常组比较,模型组大鼠肾病理显示肾小球体积增大,基底膜增厚,肾小管上皮细胞脱落;与模型组比较,补脾益肾组大鼠的肾脏病理改善。与正常组比较,模型组大鼠不同时间点随机血糖、24 h UAER、肾小管损伤相关蛋白均升高(P<0.01),肾组织SGLT1、SGLT2表达均增强(P<0.01),NKCC2、CX40、A1AR表达下降(P<0.01);与模型组比较,补脾益肾组随机血糖、24 h UAER、肾小管损伤相关蛋白均下降(P<0.01),SGLT1、SGLT2表达下调,NKCC2、CX40、A1AR表达升高(P<0.05)。结论:补脾益肾方能够改善糖尿病肾病大鼠肾小球和肾小管损伤,减轻早期高滤过,其对糖尿病肾病的干预作用与调节管球反馈有关。展开更多
文摘In this review,we focused on two molecules,connexin and sodium-glucose cotransporter,which can link to diabetic hyperfiltration.In diabetic kidney,the activation of renin-angiotensin system occurs simultaneously with glomerular hyperfiltration.The latter largely dependson pathophysiological afferent arteriolar dilation in the presence of high angiotensin Ⅱ.As a mechanistic basis for the above,tubular hypothesis has been proposed for type 1 diabetic patients as well as experimental models.Although tubular hypothesis has not been well evaluated in type 2 diabetes,clinical observations support that tubular hypothesis is true also in type 2 diabetes.Recent results on tubular hypothesis along with connexin abnormality in type 2 diabetes were revisited.In addition,the importance of sodium-glucose cotransporter in diabetic hyperfiltration is discussed.The link between salt paradox and the activation of reninangiotensin system will be also reviewed.
文摘Objective：To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods：A mathematical model is developed based on response （MR） Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic tubuloglomerular feedback （TGF） and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results：The results predict the dynamics of renal autoregulation on its blood pressure and flow, and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion ：The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.
文摘目的:观察补脾益肾方对糖尿病肾病大鼠疗效及管球反馈机制的影响。方法:100只雄性SD大鼠随机取25只作为正常组,余75只应用高脂高糖饮食联合小剂量链脲佐菌素(STZ)腹腔注射建立糖尿病大鼠模型,将成模大鼠随机均分为模型组、补脾益肾组、氯沙坦组、补脾益肾组予补脾益肾方23.4 g·kg^(-1)灌胃,氯沙坦组予氯沙坦片9 mg·kg^(-1)灌胃,正常组和模型组予以等体积蒸馏水灌胃,持续治疗11周,每2周测1次随机血糖,第11周结束后取材进行指标检测,各组大鼠放入代谢笼,记录24 h尿量。酶联免疫吸附测定法(ELISA)检测24 h尿微量白蛋白定量(24 h UAER)、肾小管损伤相关蛋白和尿肌酐,取血检测血肌酐、尿素氮;行苏木素-伊红(HE)染色、糖原(PAS)染色、马松(Masson)染色观察大鼠肾脏病理变化;免疫组化法观察大鼠肾钠-葡萄糖共转运蛋白1(SGLT1),钠-葡萄糖共转运蛋白2(SGLT2)、钠-钾-氯协同转运蛋白2(NKCC2)、缝隙连接蛋白40(CX40)表达,免疫荧光观察腺苷Ⅰ型受体(A1AR)在肾脏定位;蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)检测肾脏组织SGLT1、SGLT2、NKCC2、CX40、A1AR的表达。结果:与正常组比较,模型组大鼠肾病理显示肾小球体积增大,基底膜增厚,肾小管上皮细胞脱落;与模型组比较,补脾益肾组大鼠的肾脏病理改善。与正常组比较,模型组大鼠不同时间点随机血糖、24 h UAER、肾小管损伤相关蛋白均升高(P<0.01),肾组织SGLT1、SGLT2表达均增强(P<0.01),NKCC2、CX40、A1AR表达下降(P<0.01);与模型组比较,补脾益肾组随机血糖、24 h UAER、肾小管损伤相关蛋白均下降(P<0.01),SGLT1、SGLT2表达下调,NKCC2、CX40、A1AR表达升高(P<0.05)。结论:补脾益肾方能够改善糖尿病肾病大鼠肾小球和肾小管损伤,减轻早期高滤过,其对糖尿病肾病的干预作用与调节管球反馈有关。
