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The Study On The Combination Of Rutin And Berberine In Metabolic Syndrom

Posted on:2017-04-09Degree:MasterType:Thesis
Country:ChinaCandidate:S P XiongFull Text:PDF
GTID:2284330488988356Subject:Pharmacy
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Rutin and it’s aglycone quercetin are common flavonoids, and their role in regulating glucose and lipid metabolism has been reported by many studies. Recent years, the hypouricemic effet of rutin and quercetin has became a research hot spot. The study on berberine against insulin resistance is quite deep. On the basis of summarizing a large number of literature at home and abroad, we conducted a research about rutin and combined use of berberine on the improvement of insulin resistance in diabetic rats, and the hypouricemic effet of different doses of quercetin, rutin and combined use of berberine in hyperuricemia rats.Method:1 Creating diabetic rat model by intraperitoneal injection of STZ and high-fat diet feeding, continuously ig rutin and berberine. To observe the lipid-lowering effect by testing rats’ plasma TC, TG and LDL-C. And test-ing the content of plasma SOD, MDA and TNF-α to evaluate the efficacy of antioxidative stress and inflammatory aspects. Using gene chip technology to filter differentially expressed genes.2 Creating hyperuricemia rat model by adenine 100mg/kg and ethambutol 250mg/kg. Testing UA, XO, Cr, BUN in plasma. UA, Cr in urine and calculating FEUA, Cur and Ccr. Rat renal tissue HE staining for pathological morphology; The expression of URAT1 protein in renal tubular epithelial cells measured by immunohistochemistry.Result:According to the results of diabetes experimental, FPG is significantly increased in model rats, which indicate the diabetes model is successful. Compared to the control group, TC, TG, LDL-C, UA, MDA and TNF-α are also significantly increased in model group, while the SOD activity is significantly decreased.Compared to the model group, TC, TG, UA, MDA and TNF-a is significantly decreased, SOD activity is significantly elevated in the group of high dose composite; TC, TG, UA, LDL-C, MDA and TNF-a is significantly decreased, SOD activity is significantly elevated in the group of low dose composite. In rutin group, TC, TG, MDA is significantly decreased, SOD activity is significantly increased, but UA, LDL-C and TNF-a has no significant difference compare with model group. In berberine group, TC, LDL-C, MDA could be significantly reduced by the use of berberine, but in TG, UA, SOD and TNF-a, there is no significant effect. After gene chip testing, we foud the low dose composite could callback multiple abnormal expression genes in model group.The hyperuricemia experimental results show the serum uric acid is signif-icantly increased in model rats compared with control group after establishing model for 2 weeks, which indicate the hyperuricemia model is successfully established. After 2 weeks of drug administration, the level of serum uric acid is significantly decreased in quercetin low, medium and high dose, low dose composite and allopurinol, benzbromarone groups. But, at the end of 3 weeks of drug administration, low dose quercetin has no significant effect on hypouricemic act, uric acid of rats in other group is still significantly reduced. Rats’24 hours urine volume,24 hours total urinary uric acid and uric acid clearance is significantly increased in quercetin high dose group, allopurinol group and benzbromarone group. Besides, high dose quercetin, low dose composite, allopurinol and benzbromarone could significantly suppress the activity of X0. The result of rat renal tissue HE staining show the renal structure and the size of glomerular is normal, no mixed swelling tubular degeneration, kidney tissue cortex and medulla were not pathological changed in control group. In model group, some red red tube in renal cortex tubules is visible, there is edema in some tubular epithelial cells, degenerated like ballooning. Each treatment group have varying degrees of pathological changes. In the experiment of immunohistochemistry evaluating the expression of protein URAT1, the protein URAT1 is weakly positive expressed in kidney epithelial cells of control group. But in hyperuricemia model group, URAT1 protein is abundantly expressed in rat kidney epithelial cells. High dose Quercetin, low dose composite, benzbromarone significantly inhibit the expression of URAT1 protein.Conelusion:The effect on lipid-lowering, the efficacy of anti-inflammatory aspects of rutin in combination with berberine is better than rutin or berberine alone on diabetic rats. Berberine in combination with rutin and quercetin can significantly reduce serums uric acid in hyperuricemia rats. The mechanism could be related to the suppression on XO activity, and the inhibition on the expression of URAT1 protein in tubular epithelial cells. Rutin in combination with berberine has some prospects in the treatment of metabolic syndrome, worthy of continuing study.
Keywords/Search Tags:rutin, berberine, metabolicsyndrome, insulin resistance, hyperuricemia
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