目的探讨西伯利亚蓼醇提物降尿酸活性及对肝脏黄嘌呤氧化酶(XOD)和肾脏尿酸转运体的影响。方法连续7 d灌胃给予西伯利亚蓼醇提物2.0,4.0,8.0 g·kg-1,最后1 d腹腔注射氧嗪酸钾盐,诱导小鼠产生高尿酸血症,对比各组小鼠血清尿酸和肌...目的探讨西伯利亚蓼醇提物降尿酸活性及对肝脏黄嘌呤氧化酶(XOD)和肾脏尿酸转运体的影响。方法连续7 d灌胃给予西伯利亚蓼醇提物2.0,4.0,8.0 g·kg-1,最后1 d腹腔注射氧嗪酸钾盐,诱导小鼠产生高尿酸血症,对比各组小鼠血清尿酸和肌酐水平变化,检测肝脏XOD活性,并采用RT-PCR法检测3种肾脏尿酸转运体m RNA表达水平。结果与模型组比较,西伯利亚蓼醇提物各剂量组小鼠血清尿酸和肌酐水平均显著降低(P<0.01,P<0.001)。西伯利亚蓼低、高剂量组可显著降低小鼠肝脏XOD活性(P<0.01,P<0.001),抑制率分别为23.29%和31.12%。西伯利亚蓼醇提物各剂量组均可显著下调因氧嗪酸钾盐诱导升高的小鼠肾脏尿酸转运体GLUT9 m RNA表达水平(P<0.01),同时均显著上调OAT1 m RNA的表达(P<0.01);西伯利亚蓼醇高剂量组可显著下调URAT1 m RNA的表达(P<0.05)。结论西伯利亚蓼醇提物具有降尿酸作用,其降尿酸作用机制较为复杂,可同时通过抑制XOD减少尿酸的生成和调控尿酸转运体加速尿酸的排泄两种途径。展开更多
Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this proc...Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this process:urate transporter (URAT)1,glucose transporter (GLUT)9,organic anion transporter (OAT)1 and OAT3.Excessive fructose intake may result in increased serum urate levels.Chicory (Cichorium intybus L.) has been used as an edible vegetable and traditional Chinese medicine.Studies have shown that chicory is a promising anti-hyperuricemia agent and we explored the mechanism of its uricosuric effect via a renal pathway.Methods:Hyperuricemia was induced in rats by administration of 10% fructose.The uricosuric effect was evaluated by determining the serum urate level.Renal excretory function was detected by the clearance rate of creatinine,clearance rate of uric acid and histology.The location and expression of URAT1,GLUT9,OAT1 and OAT3 their mRNA expression in kidneys were analyzed.Results:Chicory decreased serum levels of urate and creatinine significantly,and promoted the clearance of creatinine and urate,as well as improving renal pathologic changes due to hyperuricemia.Chicory inhibited expression of URAT1 and GLUT9 markedly in a dosedependent manner,but showed no influence on expression of OAT1 or OAT3.Conclusion:Chicory might be a promising anti-hyperuricemia agent.It can promote renal excretion of urate by inhibiting urate reabsorption,which may be related to downregulation of mRNA and protein expression of URAT1 and GLUT9.展开更多
Background:Abnormally high level of uric acid in the blood,defined as hyperuricemia(HUA),increases the chance of developing various disorders,such as gout,hypertension,and diabetes.There is a critical need to create s...Background:Abnormally high level of uric acid in the blood,defined as hyperuricemia(HUA),increases the chance of developing various disorders,such as gout,hypertension,and diabetes.There is a critical need to create safer and more potent therapeutic medications since the current clinical treatment for HUA has a number of negative effects.Objective:To explore the antihyperuricemic benefits of the total flavonoids from Carya cathayensis leaves(CCTF)in HUA model mice and to elucidate the underlying mechanisms.Methods:The mouse HUA model was induced with potassium oxonate and hypoxanthine and then the mice were given normal saline,allopurinol,or various dosages of CCTF for one week.The weight of the mice was recorded,followed by measurements of their blood uric acid(UA),creatinine(Cr),urea nitrogen(BUN),aspar-tate aminotransferase(AST),alanine aminotransferase(ALT),and xanthine oxidase(XOD)activity.Hematoxylin and eosin(H&E)staining and Manson staining were used to simultaneously detect pathological abnormalities in the liver and kidney tissues.Afterward,the mRNA expression of urate transporters in kidney was determined by qRT‒PCR experiments,including ATP-binding cassette transporter subfamily G member 2(Abcg2),urate trans-porter 1(Urat1),and glucose transporter 9(Glut9).Finally,immunohistochemistry(IHC)staining was performed to confirm ABCG2 protein expression in the kidney.Results:In contrast to the model group,the CCTF group lowered blood levels of UA,Cr,BUN,ALT,and AST in serum,downregulated XOD levels in serum and liver,and significantly improved liver and renal damage,exhibiting outstanding antihyperuricemic effects.The levels of Urat1 and Glut9 were further shown to be much lower in the kidney,whereas both Abcg2 expression and ABCG2 level were increased,according to the findings.Conclusion:CCTF ameliorated hyperuricemia-related kidney damage and had antihyperuricemic effects,suggest-ing that CCTF might have the potential to protect against HUA by regulating the expression of relative urate transporters and 展开更多
Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this st...Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this study aimed to investigate the potential mechanism of the hyperuricemic inhibitory effects of lotus leaf crude extract(LL)and lotus leaf total alkaloids fraction(LA).Methods:The xanthine oxidase(XOD)inhibitory effect of LL and LA was analyzed in vitro by determining mRNA expression and protein expression levels of hepatic XOD.The hyperuricemic inhibitory effect of the lotus leaf was analyzed in vivo in a potassium oxonate(PO)-induced rat model by determining mRNA expression for renal urate transporters.Results:At a concentration of 40mg/mL,LL and LA suppressed XOD enzymatic activity by 37.35%±9.50%and 47.73%±8.32%,respectively.Both LL and LA administration significantly reduced the concentration of uric acid in the serum and liver of PO-induced hyperuricemic rats.Both LL and LA administration could inhibit XOD mRNA and protein expression,activate renal organic anion transporter 1/3 mRNA expression,and inhibit renal urate reabsorption by decreasing renal GLUT9 and renal urate transporter 1.Conclusions:Insight was gained into the mechanism behind the hyperuricemic inhibitory effects of LL and LA.Our results suggest that they act on two targets:decreasing the production of uric acid by inhibiting mRNA and protein expression of XOD in the liver,and regulating the mRNA expression of renal urate transporters in the kidneys.展开更多
尿酸代谢异常被看作是高尿酸血症和痛风的主要病因之一,尿酸盐转运蛋白的功能异常是导致尿酸代谢异常的最主要原因,其影响了肾脏对尿酸的重吸收和排泄功能。近年来三磷酸腺苷结合盒转运蛋白G2(ATP-binding cassette superfamily G membe...尿酸代谢异常被看作是高尿酸血症和痛风的主要病因之一,尿酸盐转运蛋白的功能异常是导致尿酸代谢异常的最主要原因,其影响了肾脏对尿酸的重吸收和排泄功能。近年来三磷酸腺苷结合盒转运蛋白G2(ATP-binding cassette superfamily G member 2,ABCG2)作为最受关注的尿酸盐转运蛋白,得到国外国内学者的较多研究报道。ABCG2定位在细胞膜,表达在近曲小管上皮细胞刷状缘侧,可以转运尿酸。其功能性障碍阻碍了肾脏和肠道对尿酸的排泄,从而引起高尿酸血症并引发痛风。本文就ABCG2基因单核苷酸多态性与痛风发病相关性的研究进展作一综述。展开更多
文摘目的探讨西伯利亚蓼醇提物降尿酸活性及对肝脏黄嘌呤氧化酶(XOD)和肾脏尿酸转运体的影响。方法连续7 d灌胃给予西伯利亚蓼醇提物2.0,4.0,8.0 g·kg-1,最后1 d腹腔注射氧嗪酸钾盐,诱导小鼠产生高尿酸血症,对比各组小鼠血清尿酸和肌酐水平变化,检测肝脏XOD活性,并采用RT-PCR法检测3种肾脏尿酸转运体m RNA表达水平。结果与模型组比较,西伯利亚蓼醇提物各剂量组小鼠血清尿酸和肌酐水平均显著降低(P<0.01,P<0.001)。西伯利亚蓼低、高剂量组可显著降低小鼠肝脏XOD活性(P<0.01,P<0.001),抑制率分别为23.29%和31.12%。西伯利亚蓼醇提物各剂量组均可显著下调因氧嗪酸钾盐诱导升高的小鼠肾脏尿酸转运体GLUT9 m RNA表达水平(P<0.01),同时均显著上调OAT1 m RNA的表达(P<0.01);西伯利亚蓼醇高剂量组可显著下调URAT1 m RNA的表达(P<0.05)。结论西伯利亚蓼醇提物具有降尿酸作用,其降尿酸作用机制较为复杂,可同时通过抑制XOD减少尿酸的生成和调控尿酸转运体加速尿酸的排泄两种途径。
基金The authors thank Mrs.Meijuan Yang for her technical support on the preparation of paraffin sections.This work was supported by National Natural Science Foundation of China(81673618)Beijing Natural Science Foundation(7162117)National Science and Technology Major Projects for'Major New Drugs Innovation and Development'(2017ZX09301024).
文摘Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this process:urate transporter (URAT)1,glucose transporter (GLUT)9,organic anion transporter (OAT)1 and OAT3.Excessive fructose intake may result in increased serum urate levels.Chicory (Cichorium intybus L.) has been used as an edible vegetable and traditional Chinese medicine.Studies have shown that chicory is a promising anti-hyperuricemia agent and we explored the mechanism of its uricosuric effect via a renal pathway.Methods:Hyperuricemia was induced in rats by administration of 10% fructose.The uricosuric effect was evaluated by determining the serum urate level.Renal excretory function was detected by the clearance rate of creatinine,clearance rate of uric acid and histology.The location and expression of URAT1,GLUT9,OAT1 and OAT3 their mRNA expression in kidneys were analyzed.Results:Chicory decreased serum levels of urate and creatinine significantly,and promoted the clearance of creatinine and urate,as well as improving renal pathologic changes due to hyperuricemia.Chicory inhibited expression of URAT1 and GLUT9 markedly in a dosedependent manner,but showed no influence on expression of OAT1 or OAT3.Conclusion:Chicory might be a promising anti-hyperuricemia agent.It can promote renal excretion of urate by inhibiting urate reabsorption,which may be related to downregulation of mRNA and protein expression of URAT1 and GLUT9.
基金The Zhejiang Traditional Chinese Medicine Administration(CN)(Project No.2023ZF012).
文摘Background:Abnormally high level of uric acid in the blood,defined as hyperuricemia(HUA),increases the chance of developing various disorders,such as gout,hypertension,and diabetes.There is a critical need to create safer and more potent therapeutic medications since the current clinical treatment for HUA has a number of negative effects.Objective:To explore the antihyperuricemic benefits of the total flavonoids from Carya cathayensis leaves(CCTF)in HUA model mice and to elucidate the underlying mechanisms.Methods:The mouse HUA model was induced with potassium oxonate and hypoxanthine and then the mice were given normal saline,allopurinol,or various dosages of CCTF for one week.The weight of the mice was recorded,followed by measurements of their blood uric acid(UA),creatinine(Cr),urea nitrogen(BUN),aspar-tate aminotransferase(AST),alanine aminotransferase(ALT),and xanthine oxidase(XOD)activity.Hematoxylin and eosin(H&E)staining and Manson staining were used to simultaneously detect pathological abnormalities in the liver and kidney tissues.Afterward,the mRNA expression of urate transporters in kidney was determined by qRT‒PCR experiments,including ATP-binding cassette transporter subfamily G member 2(Abcg2),urate trans-porter 1(Urat1),and glucose transporter 9(Glut9).Finally,immunohistochemistry(IHC)staining was performed to confirm ABCG2 protein expression in the kidney.Results:In contrast to the model group,the CCTF group lowered blood levels of UA,Cr,BUN,ALT,and AST in serum,downregulated XOD levels in serum and liver,and significantly improved liver and renal damage,exhibiting outstanding antihyperuricemic effects.The levels of Urat1 and Glut9 were further shown to be much lower in the kidney,whereas both Abcg2 expression and ABCG2 level were increased,according to the findings.Conclusion:CCTF ameliorated hyperuricemia-related kidney damage and had antihyperuricemic effects,suggest-ing that CCTF might have the potential to protect against HUA by regulating the expression of relative urate transporters and
基金supported by the Program for New Century Excellent Talents in University(NCET-10-0958,NCET-12-1069)Important Drug Develop of MOST,China(2011ZX09307-002-01)National Natural Science Foundation of China(81173524).
文摘Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this study aimed to investigate the potential mechanism of the hyperuricemic inhibitory effects of lotus leaf crude extract(LL)and lotus leaf total alkaloids fraction(LA).Methods:The xanthine oxidase(XOD)inhibitory effect of LL and LA was analyzed in vitro by determining mRNA expression and protein expression levels of hepatic XOD.The hyperuricemic inhibitory effect of the lotus leaf was analyzed in vivo in a potassium oxonate(PO)-induced rat model by determining mRNA expression for renal urate transporters.Results:At a concentration of 40mg/mL,LL and LA suppressed XOD enzymatic activity by 37.35%±9.50%and 47.73%±8.32%,respectively.Both LL and LA administration significantly reduced the concentration of uric acid in the serum and liver of PO-induced hyperuricemic rats.Both LL and LA administration could inhibit XOD mRNA and protein expression,activate renal organic anion transporter 1/3 mRNA expression,and inhibit renal urate reabsorption by decreasing renal GLUT9 and renal urate transporter 1.Conclusions:Insight was gained into the mechanism behind the hyperuricemic inhibitory effects of LL and LA.Our results suggest that they act on two targets:decreasing the production of uric acid by inhibiting mRNA and protein expression of XOD in the liver,and regulating the mRNA expression of renal urate transporters in the kidneys.
文摘尿酸代谢异常被看作是高尿酸血症和痛风的主要病因之一,尿酸盐转运蛋白的功能异常是导致尿酸代谢异常的最主要原因,其影响了肾脏对尿酸的重吸收和排泄功能。近年来三磷酸腺苷结合盒转运蛋白G2(ATP-binding cassette superfamily G member 2,ABCG2)作为最受关注的尿酸盐转运蛋白,得到国外国内学者的较多研究报道。ABCG2定位在细胞膜,表达在近曲小管上皮细胞刷状缘侧,可以转运尿酸。其功能性障碍阻碍了肾脏和肠道对尿酸的排泄,从而引起高尿酸血症并引发痛风。本文就ABCG2基因单核苷酸多态性与痛风发病相关性的研究进展作一综述。
