| Hyperuricemia is caused by uric acid excretion disorder.It is about 70% of uric acid excrete through the kidney Which is mainly dependent on renal epithelial cell transporter.The uric acid transporters in the kidney have been investigated for many years.There are still about 30% uric acid can be excreted through the intestinal,However,we have little mechanistic study on intestinal “extra-renal excretion”pathway of uric acid before the finding of uric acid transporters.Intestinal epithelial cells are also distributed in a variety of transporters,including some transporters involved in renal uric acid excretion.But its role in uric acid excretion is not clear.This study was to investigate the possible effects of rhein on intestinal transporters and intestinal uric acid excretion,and try to reveal the molecular mechanism.The main research work of the paper is summarized as follows:1.Effects of fructose on the m RNA expression of uric acid transport-related transporter in Caco-2 cellsIn this study,Caco-2 cells were stimulated by different concentrations of fructose solution,and the effect of fructose on the m RNA expression of intestinal epithelial cell transporter m RNA was detected by real time-PCR.The results showed that when the fructose concentration was 60 ?M,the expression of MCT9,ABCG2 and GLUT9 m RNA could be stimulated,the expression of transporter MRP2 transporter m RNA could be inhibited,suggesting that the reason of hyperuricemia caused by high fructose diet may be up-regulate the expression of GLUT9 m RNA to increases the reabsorption of uric acid and down-regulate the expression of MRP2 m RNA to reduce uric acid excretion.2.Effects of rhein on the m RNA expression of uric acid transporters in intestinal epithelial cells after being stimulated by fructose.The results showed that when the concentration of rhein was 0~5 mg·L-1,the cell activity was not decreased at each time point.To be sure the cells was in a normal state.And the concentrations of rhein selected for subsequent tests were kept below5 mg·L-1.After stimulated by fructose,the concentration of rhein at 2.5 mg·L-1and5 mg·L-1 are significantly up-regulated the m RNA expression of MRP2,down-regulated the m RNA expression of GLUT9.Which is prompts that rhein is increase intestinal uric acid excretion and reduce intestinal uric acid reabsorption to achieve the effect of uric acid.3.Studies on the permeation mechanism of uric acid in Caco-2 cell monolayersCaco-2 cells were seeded on the Transwell plate for 21 days and then autonomously differentiated into small intestinal epithelial cells.To study the effects of different absorption and transport regulators on uric acid permeation.The results showed that the GLUT9,MRP2 and ABCG2 proteins regulate permeation of the uric acid in the small intestine,and the MRP2 protein and ABCG2 protein can increase the excretion of uric acid from the blood to the enteric cavity.The GLUT9 protein can reduce the reabsorption of uric acid from the enteric cavity to the blood.4.Studies on the effects of rhein on uric acid excretion of hyperuricemia animal model which is also acute renal insufficiency and its mechanism.The right kidney was removed by surgery and intraperitoneally injected with oxalate potassium salt to make animal model and studies on the effects of rhein on uric acid excretion through intestine.Detectde the m RNA expression of transporter by real time-PCR.The results showed that rhein can increase intestinal uric acid excretion to reduce serum uric acid concentration in the case of renal damage.The mechanism of action is mainly to reduce the m RNA expression of GLUT9 to reduced uric acid reabsorption.We conclude that GLUT9,MRP2,ABCG2 also play a role in intestinal uric acid excretion,and rhein is mainly by down-regulated the expression of GLUT9 m RNA to reduce uric acid. |
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