| Objective:To explore the approach to build persistent animal model of hyperuricemia on rat and to observe the influence of continuous hyperuricemia on isletβcells in rats.Methods:35 male and 35 female Wistar rats of 8 weeks age were raised up to 9 weeks age on ordinary diet, female rats were divided into 2 groups randomly:control group (n=15)and model group(n=20), the model group was administered with 10% hyperyeast animal feeds and adenine(100mg/kg/d) by gavage daily. Blood UA was detected every week regularly. To improve the modeling methods when serum uric acid levels started to decline. The model group was administrated with adenine 50mg/(kg-d) by gavage and 10% hyperyeast animal feeds, meanwhile Oxonic Acid 100mg/(kg-d) were injected beneath the skin twice a day. The male rats were given the same treatment. The control group was administered on ordinary diet. UA,BG, TG,TC,CRE,BUN and 24h urine volume and UUA were detected regularly. Insulin were detected by radioimmunity. The fluctuation of blood glucose and insulin was compared between control group and model group. When the blood glucose of modle group stepped up and was significantly higher than that of control group, kept the model group and part of the control group rats of female alive and executed other rats, divided the model group rats of female into 2 groups:one was given high purine diet as before, other was administered with ordinary animal feeds. Pancreases and kidneys were made paraffin section, the content of insulin were detected by immunohistochemistry. The data was analyzed by t-test and P<0.05 was considered significant.Results:①On the 10th day of high purine diet, blood uric acid level of both female and male model group were significantly higher than their corresponding control group (t=4.799-17.04,P<0.05). There was no persistent statistics differences on blood uric acid level between female and male model group (2-6w,9w,t=2.701-4.119,p<0.05;0w,1w,7w,8w,10-12w, t=0.639-1.810, p>0.05);②On the 70th day of intervention, the fasting blood glucose level of the female model group was significantly higher than that of the control group(t=2.909-12.806,p<0.05), and the same condition of male group was happened on the 77th day (t=2.909-12.806,p<0.05); the differences between the two groups on the blood glucose level of OGTT2h in the female group appeared on the 63th day(t=4.204-13.539,p<0.05), the same time as the male group(t=5.796-10.455,p<0.05).③On the 10th day of intervention, there was persistent statistics difference on the fasting and OGTT2h insulin level of both female and male rats (t=2.911-13.37,p<0.05).④On the 21th day of no intervention, the blood uric acid and blood glucose level of female group which was stopped high purine diet was decreased obviously, there was statistics differences on the fasting and OGTT2h blood glucose level (t=8.565-10.957, p<0.05) but no statistics differences on blood uric acid level between the two groups (t=2.135, p>0.05).⑤The expression of insulin was detected in all slices. Compared with the control group, the shape of islet in model group becomes irregular,the number of islet and the dyeing area of insulin decreased obviously in both female and male rats.Conclusion:①The approach of replicating persistent animal model of hyperuricemia on rat by using adenine yeast and uricase inhibitor is effective, the uric acid on serum can be maintained steadily at a high level for a long time.②Persistent hyperuricemia can cause hyperglycaemia on rats. It is probably because that persistent hyperuricemia causes damage and induces apoptosis on islet Pcells in rats. |
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