BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To invest...BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.展开更多
The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in...The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg^(-1) potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg^(-1) was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase(XDH) and xanthine oxidase(XOD), regulated renal m RNA and protein levels of urate transporter 1(URAT1), glucose transporter 9(GLUT9), organic anion transporter 1(OAT1), organic cation transporter 1(OCT1), OCT2, organic cation/carnitine transporter 1(OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3(NLRP3), apoptosis-associated speck-like(ASC), and Caspase-1, resulting in the reduction of interleukin(IL)-1β, IL-18, IL-6 and tumor necrosis factor-α(TNF-α) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.展开更多
目的:观察刺络泻血疗法对高尿酸血症模型大鼠血尿酸及相关酶活性的影响并探讨其机制。方法:将40只清洁级SD大鼠分为正常组、模型组、别嘌呤醇组及刺络泻血组,每组10只,以腺嘌呤、盐酸乙胺丁醇混合液灌胃造模。第4周造模成功后,别嘌呤醇...目的:观察刺络泻血疗法对高尿酸血症模型大鼠血尿酸及相关酶活性的影响并探讨其机制。方法:将40只清洁级SD大鼠分为正常组、模型组、别嘌呤醇组及刺络泻血组,每组10只,以腺嘌呤、盐酸乙胺丁醇混合液灌胃造模。第4周造模成功后,别嘌呤醇组按照0.03 g/(kg·d)的剂量给大鼠灌胃别嘌呤醇,2次/周;刺络泻血组选取大鼠委中穴及足三里穴穴位附近的血络,出血0.3~0.5 m L,至第8周。第9周后腹主动脉取血,采用磷钨酸法测定血尿酸,采用酶比色法测定黄嘌呤氧化酶(XOD)和腺苷脱氨酶(ADA)的含量。结果:实验结束后,与正常组相比,模型组SUA、ADA、XOD含量均显著增高(P<0.05),差异有统计学意义;与模型组相比,别嘌呤醇组SUA、XOD含量显著降低(P<0.05),刺络泻血组SUA、ADA、XOD含量差异均有统计学意义(P<0.05)。结论:刺络泻血疗法可以有效抑制XOD、ADA活性,降低高尿酸血症大鼠SUA水平。展开更多
基金Supported by National Natural Science Foundation of China,No.8187150391 and No.81904126Science and Technology Commission of Shanghai Municipality,No.20Y21901800.
文摘BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.
基金supported by grants from Program for Changjiang Scholars and Innovative Research Team in University(IRT_14R271020)
文摘The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg^(-1) potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg^(-1) was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase(XDH) and xanthine oxidase(XOD), regulated renal m RNA and protein levels of urate transporter 1(URAT1), glucose transporter 9(GLUT9), organic anion transporter 1(OAT1), organic cation transporter 1(OCT1), OCT2, organic cation/carnitine transporter 1(OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3(NLRP3), apoptosis-associated speck-like(ASC), and Caspase-1, resulting in the reduction of interleukin(IL)-1β, IL-18, IL-6 and tumor necrosis factor-α(TNF-α) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.
文摘目的:观察刺络泻血疗法对高尿酸血症模型大鼠血尿酸及相关酶活性的影响并探讨其机制。方法:将40只清洁级SD大鼠分为正常组、模型组、别嘌呤醇组及刺络泻血组,每组10只,以腺嘌呤、盐酸乙胺丁醇混合液灌胃造模。第4周造模成功后,别嘌呤醇组按照0.03 g/(kg·d)的剂量给大鼠灌胃别嘌呤醇,2次/周;刺络泻血组选取大鼠委中穴及足三里穴穴位附近的血络,出血0.3~0.5 m L,至第8周。第9周后腹主动脉取血,采用磷钨酸法测定血尿酸,采用酶比色法测定黄嘌呤氧化酶(XOD)和腺苷脱氨酶(ADA)的含量。结果:实验结束后,与正常组相比,模型组SUA、ADA、XOD含量均显著增高(P<0.05),差异有统计学意义;与模型组相比,别嘌呤醇组SUA、XOD含量显著降低(P<0.05),刺络泻血组SUA、ADA、XOD含量差异均有统计学意义(P<0.05)。结论:刺络泻血疗法可以有效抑制XOD、ADA活性,降低高尿酸血症大鼠SUA水平。
