Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male ...Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male Kunming mice were divided into the healthy group (carboxymethylcellulose sodium at a dose of 250 mg/kg), the model group (HUA mice were given carboxymethylcellulose sodium at a dose of 250 mg/kg), the low group (HUA mice were given pueraria isoflavone at a dose of 125 mg/kg), HUA mice were given pueraria isoflavones at a dose of 250 mg/kg once d frequency)and the high group (HUA mice were given pueraria isoflavones at a dose of 500 mg/kg once d frequency) dosage groups, with 8 mice in each group. The contents of uric acid (SUA), urea nitrogen (BUN) and creatinine (SCr) in serum and urine of each group were compared before and after intervention (30 d). Statistical differences of xanthine oxidase (XOD) and human glucose transporter 9(GLUT9), cy- clooxygenase- 2(COX-2), tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) contents in renal tissues of each group after intervention (30 d) were compared. Results: After intervention, kidney inflammatory factors (COX-2, TNF-α and IL-1β) in the model group were compared. Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were higher than those of healthy group(P<0.05). Renal inflammatory cytokines (COX-2, TNF-α and IL-1β) in low, medium and high dose groups;Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were lower than those of model group, and there were low > medium > high dose groups, the comparison between the two groups had statistical significance(P< 0.05). After intervention, the contents of 3 indicators in blood or urine(COX-2, TNF-α and IL-1β) all decreased compared with before intervention, and the differences in intra-group comparison were statistically significant (P<0.05). Conclusion: Pueraria isoflavones can treat HUA mice by inhibiting the expression of XOD and GLUT9, and then play a role in reducing uric acid pro- duction and promoting uric acid excretion, as well as alleviating the degree of disease inflammation.展开更多
Objective： To explore the effect of Compound Tufuling Granules （复方土茯苓颗粒, CTG） on regulating glucose transporter 9 （GLUT9） expression in the kidney to influence the uric acid excretion by the kidney and ser...Objective： To explore the effect of Compound Tufuling Granules （复方土茯苓颗粒, CTG） on regulating glucose transporter 9 （GLUT9） expression in the kidney to influence the uric acid excretion by the kidney and serum uric acid （SUA） level in hyperuricemia mice. Methods： Sixty Kunming male mice were randomly divided into the control group, model group, benzbromarone group, and CTG high-, middle- and low- dose groups. The yeast extract and uricase inhibition method were used to build hyperuricemia model, and the corresponding drugs were administrated on the 7th day. On the 21st day the 24-h urine was collected, on the 22rid day the blood was collected, the SUA level was detected by uricase colorimetry, and the mRNA and protein expressions of GLUT9 were detected by quantitative real-time polymerase chain reaction and Western blot, respectively. Results： Compared with the model group, the levels of SUA and the mRNA and protein expressions of GLUT9 were significantly decreased, and the fraction excretion of uric acid （FEUA） was significantly increased in the CTG groups and benzbromarone group （all P〈0.05）. There was no significant difference in the above indicators between the CTG high-dose group and benzbromarone group （P〉0.05）. SUA is positively related to the GLUT9 mRNA and protein expressions in the kidney （P〈0.05 or P〈0.01）. Conclusions： CTG can significantly reduce the SUA and increase the FEUA. In addition, CTG can effectively inhibit the mRNA and protein expressions of GLUT9 in the kidney of hyperuricemia mice to inhibit the uric acid re-absorption, promote uric acid excretion and reduce SUA.展开更多
Objective:To observe whether CAV3 is involved in the physiological process of IMGU and NIMGU.Down-regulation of caveolin-3(CAV3)protein expression by small interference RNAs(iRNA)has been studied.Insulin-mediated gluc...Objective:To observe whether CAV3 is involved in the physiological process of IMGU and NIMGU.Down-regulation of caveolin-3(CAV3)protein expression by small interference RNAs(iRNA)has been studied.Insulin-mediated glucose uptake(IMGU)is critical in skeletal muscle and cardiac myocytes,but non-insulin-mediated glucose uptake(NIMGU)should not be neglected.Methods:CAV3 siRNAs were designed and transfected in C2C12 cells and H9c2 cells in skeletal muscle and cardiac muscle,respectively,and C2C12 and H9c2 cells were cultured in DMEM medium with and without insulin,respectively.Glucose transporter 4(GLUT4)protein expression was detected by Western blot,and the glucose uptake rate of cells was measured by biochemical kit.Results:Transfection with CAV3 siRNA successfully down-regulated CAV3 protein expression in C2C12 and H9c2 cells.In the absence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.05)after 48 h of transfection in C2C12 cells,and GLUT4 expression was decreased(P<0.05)and glucose uptake was reduced(P<0.01)after 48 h of transfection in H9c2 cells.In the presence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.01)after 48 h of transfection in C2C12 cells,and the downregulation of GLUT4 was not statistically significant and glucose uptake was reduced(P<0.01)after 48 hours of transfection in H9c2 cells.Conclusion:Two different states,IMGU and NIMGU,exist in C2C12 cells and H9c2 cells.Both in the quiet state stimulated by insulin as well as in the absence of insulin stimulation,the cellular uptake of glucose is affected by GLUT4 changes regulated by CAV3.展开更多
基金National Innovation and Entrepreneurship Training Program for College Students(No.S202010823014)Hunan Provincial College Student Innovation Training Project,No.(2021)199(S202110823045)。
文摘Objective: To analyze the possible mechanism of Pueraria isoflavones inhibiting XOD and GLUT9 to reduce uric acid production and promote uric acid excretion. Methods: August 2021-April 2022, a total of forty SPF male Kunming mice were divided into the healthy group (carboxymethylcellulose sodium at a dose of 250 mg/kg), the model group (HUA mice were given carboxymethylcellulose sodium at a dose of 250 mg/kg), the low group (HUA mice were given pueraria isoflavone at a dose of 125 mg/kg), HUA mice were given pueraria isoflavones at a dose of 250 mg/kg once d frequency)and the high group (HUA mice were given pueraria isoflavones at a dose of 500 mg/kg once d frequency) dosage groups, with 8 mice in each group. The contents of uric acid (SUA), urea nitrogen (BUN) and creatinine (SCr) in serum and urine of each group were compared before and after intervention (30 d). Statistical differences of xanthine oxidase (XOD) and human glucose transporter 9(GLUT9), cy- clooxygenase- 2(COX-2), tumor necrosis factor (TNF-α) and interleukin-1 (IL-1β) contents in renal tissues of each group after intervention (30 d) were compared. Results: After intervention, kidney inflammatory factors (COX-2, TNF-α and IL-1β) in the model group were compared. Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were higher than those of healthy group(P<0.05). Renal inflammatory cytokines (COX-2, TNF-α and IL-1β) in low, medium and high dose groups;Blood and urine indexes (SUA, BUN, SCr);The contents of XOD and GLUT9 were lower than those of model group, and there were low > medium > high dose groups, the comparison between the two groups had statistical significance(P< 0.05). After intervention, the contents of 3 indicators in blood or urine(COX-2, TNF-α and IL-1β) all decreased compared with before intervention, and the differences in intra-group comparison were statistically significant (P<0.05). Conclusion: Pueraria isoflavones can treat HUA mice by inhibiting the expression of XOD and GLUT9, and then play a role in reducing uric acid pro- duction and promoting uric acid excretion, as well as alleviating the degree of disease inflammation.
基金Supported by the National Natural Science Foundation of China(No.81072915)Science and Technology Planning Project of Guangdong Province,China(No.2012A080201012)Natural Science Foundation of Guangdong Province,China(No.S2012010009032)
文摘Objective： To explore the effect of Compound Tufuling Granules （复方土茯苓颗粒, CTG） on regulating glucose transporter 9 （GLUT9） expression in the kidney to influence the uric acid excretion by the kidney and serum uric acid （SUA） level in hyperuricemia mice. Methods： Sixty Kunming male mice were randomly divided into the control group, model group, benzbromarone group, and CTG high-, middle- and low- dose groups. The yeast extract and uricase inhibition method were used to build hyperuricemia model, and the corresponding drugs were administrated on the 7th day. On the 21st day the 24-h urine was collected, on the 22rid day the blood was collected, the SUA level was detected by uricase colorimetry, and the mRNA and protein expressions of GLUT9 were detected by quantitative real-time polymerase chain reaction and Western blot, respectively. Results： Compared with the model group, the levels of SUA and the mRNA and protein expressions of GLUT9 were significantly decreased, and the fraction excretion of uric acid （FEUA） was significantly increased in the CTG groups and benzbromarone group （all P〈0.05）. There was no significant difference in the above indicators between the CTG high-dose group and benzbromarone group （P〉0.05）. SUA is positively related to the GLUT9 mRNA and protein expressions in the kidney （P〈0.05 or P〈0.01）. Conclusions： CTG can significantly reduce the SUA and increase the FEUA. In addition, CTG can effectively inhibit the mRNA and protein expressions of GLUT9 in the kidney of hyperuricemia mice to inhibit the uric acid re-absorption, promote uric acid excretion and reduce SUA.
基金This study was supported by the National Natural Science Foundation of China(No.81660360)The Natural Science Foundation of Guangxi(No.2019JJA140605)。
文摘Objective:To observe whether CAV3 is involved in the physiological process of IMGU and NIMGU.Down-regulation of caveolin-3(CAV3)protein expression by small interference RNAs(iRNA)has been studied.Insulin-mediated glucose uptake(IMGU)is critical in skeletal muscle and cardiac myocytes,but non-insulin-mediated glucose uptake(NIMGU)should not be neglected.Methods:CAV3 siRNAs were designed and transfected in C2C12 cells and H9c2 cells in skeletal muscle and cardiac muscle,respectively,and C2C12 and H9c2 cells were cultured in DMEM medium with and without insulin,respectively.Glucose transporter 4(GLUT4)protein expression was detected by Western blot,and the glucose uptake rate of cells was measured by biochemical kit.Results:Transfection with CAV3 siRNA successfully down-regulated CAV3 protein expression in C2C12 and H9c2 cells.In the absence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.05)after 48 h of transfection in C2C12 cells,and GLUT4 expression was decreased(P<0.05)and glucose uptake was reduced(P<0.01)after 48 h of transfection in H9c2 cells.In the presence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.01)after 48 h of transfection in C2C12 cells,and the downregulation of GLUT4 was not statistically significant and glucose uptake was reduced(P<0.01)after 48 hours of transfection in H9c2 cells.Conclusion:Two different states,IMGU and NIMGU,exist in C2C12 cells and H9c2 cells.Both in the quiet state stimulated by insulin as well as in the absence of insulin stimulation,the cellular uptake of glucose is affected by GLUT4 changes regulated by CAV3.
