高尿酸血症诱发糖代谢紊乱大鼠胰岛细胞功能变化

目的观察高尿酸血症（HUA）诱发糖代谢紊乱大鼠胰岛细胞功能的变化,探讨HUA诱发和加重糖代谢紊乱的发病机制。方法健康雄性Wistar大鼠66只,随机分为正常对照组（NC组）、糖尿病（DM组）和HUA组。采用高酵母饲料饲养、腺嘌呤溶液灌胃及皮下注射氧嗪酸钾溶液的方法建立HUA诱发糖代谢紊乱大鼠模型,采用高糖高脂饲料饲养、腹腔注射链脲佐菌素（STZ）的方法建立DM组大鼠模型,每隔2周测定大鼠空腹血糖、空腹血清尿酸的水平;通过酶联免疫吸附法（ELISA法）测定空腹血清胰岛素、胰高血糖素的水平;苏木精-伊红（HE）染色和胰岛细胞双重染色观察持续HUA对胰岛组织学形态及胰岛α、β细胞占胰岛比例的影响。结果HUA组大鼠4、8、12、16周空腹血糖、空腹血清尿酸水平明显升高,与0周比较差异有显著性（F=11.933、17.606,q=3.632-7.342,P〈0.01）;HUA组大鼠第8、12周空腹血清胰岛素水平均较0周显著升高（F=4.680,q=1.916、2.035,P〈0.01）,至第16周差异无显著性（P〉0.05）;HUA组大鼠0、4、8、12周空腹血清胰高血糖素水平无明显变化（P〉0.05）,16周降低,与0周比较差异有显著性（F=3.409,q=1.623,P〈0.01）;HUA组与NC组比较,空腹血糖、血清尿酸、血清胰岛素、血清胰高血糖素在0周时差异均无显著意义（P〉0.05）,16周时差异有显著意义（t=-2.569-11.854,P〈0.05）。HE染色显示,NC组胰岛大小不等,分布均匀,形态规则,无水肿,胰岛细胞正常;DM组胰岛分布弥散,胰岛数量明显减少,部分胰岛轻度肿胀;HUA组与NC组比较胰岛形状变得不规则,胰岛数目减少,但仍然较DM组多。HUA组第16周胰岛α、β细胞分布比例与NC组比较无明显变化（P〉0.05）;HUA组内0、4、8、12、16周不同时间胰岛α、β细胞所占比例动态变化无显著差异（P〉0.05）。结论实验性HUA诱发糖代谢紊乱的机制可能主要与胰岛素抵抗、胰岛β细?

EFFECTS ON ISLET CELLS IN DYSGLYCEMIA RATS INDUCED BY HYPERURICEMIA

Objective To observe the changes of islet cell function in rats with glycometabolism disorder induced by hyperuricemia. Methods Sixty-six Wistar rats were equally radomized to three groups as normal control group,diabetes mellitus group（DM group）and hyperuricemia group.Fasting blood glucose（FBG）and serum uric acid（UA）were measure every two weeks.The levels of fasting insulin（FINS）and glucagons were detected by ELISA.Serial paraffin-embedded sectioning with double staining of islet cells and hematoxylin/eosin staining were applied to observe the the morphology,quantity and distribution of the islet cells. Results In the hyperuricemia group,the levels of FINS and UA in weeks 4,8,12 and 16increased obviously as compared with that in in week 0（F=11.933,17.606;q=3.632-7.342;P〈0.01）,in weeeks 8and 12,the levels of serum insulin elevated markedly as compared with that in week 0（F=4.680;q=1.916,2.035;P〈0.01）,the difference became not significant when reaching week 16（P〉0.05）,the levels of serum glucagon in weeks 0-12 were not significanly changed（P〉0.05）,and in week 16,the levels of serum glucagon delined,the difference was significant as compared with that in week 0（F=3.409,q=1.623,P〈0.01）.A comparison between hyperuricemia group and the NC group showed no significat difference in week 0in terms of levels of fasting UA,FBG,FINS and fasting serum glucagons（P〉0.05）,while in week 16,the difference was significant（t=-2.569-11.854,P〈0.05）.HE staining showed that in the NC group,the islet cells were normal,the size was unequal,even distribution,regular in shape,no edema;in the DM group,the distribution of islet cells was diffused,the number of the cells markedly decreased,some showed slight swelling.Compared with NC group,the shape of the islet cells in hyperuricemia group became irregular,the number of islet cells decreased-but still more than that in the DM group.In week 16,the difference of distribution of proportion ofαandβcells between hyperuricemia group and NC