氨基胍、黄芩苷对糖尿病大鼠组织非酶糖化及视网膜细胞凋亡的影响

目的研究非酶糖化、凋亡相关蛋白Bcl-2和Bax与糖尿病视网膜病变（DR）的关系，探讨非酶糖化抑制剂氨基胍和具有非酶糖化抑制作用的中药黄芩苷干预治疗，对DR的治疗作用。方法雄性Wistar大鼠40只，随机平均分为4组，正常对照组、糖尿病组、糖尿病氨基胍（100mg／kg·d）治疗组、糖尿病黄芩苷（150mg／kg·d）治疗组，腹腔注射链脲佐菌素（60mg／kg）诱发糖尿病。16周后，处死大鼠，分离主动脉，测定组织非酶糖化，观察视网膜Bcl-2、Bax的表达，电镜观察细胞凋亡的形态学变化。结果①与正常对照组相比，糖尿病组非酶糖化明显升高（P〈0．001），氨基胍治疗组、黄芩苷治疗组较糖尿病组非酶糖化明显降低（P〈0．01），而血糖无明显变化；②糖尿病组视网膜Bcl-2蛋白表达明显减少、Bax蛋白表达明显增加．氨基治疗组、黄芩苷治疗组的Bcl-2蛋白表达明显增加、Bax蛋白表达较糖尿病组明显减少；③透射电镜下见糖尿病视网膜组神经节细胞呈典型的凋亡形态学改变，氨基胍治疗组、黄芩苷治疗组大鼠组织细胞凋亡改变明显减轻。结论①非酶糖化通过调节Bcl-2，Bax蛋白的表达诱导细胞凋亡，而参与DR的发生与发展；②非酶糖化抑制剂通过抑制非酶糖化，调节Bax、Bcl-2的表达抑制细胞凋亡，延缓DR的发展；③黄芩苷对非酶糖化抑制作用与典型非酶糖化抑制剂氨基胍相似，且价格低、副作用少，值得临床推荐应用。

The effect of amioguanidine and baicalin on tissue nonenzymatic glycation and retinal apoptosis in diabetic rats

Objective By studying the relationship between tissue nonenzymatic glycation, apoptosis relative protein Bcl-2,Bax and diabetic retinopathy ,to explore the treatment effect of nonenzymatic glycation inhibitors on diabetic retinopathy. Materials and. Methods 40 male Wistar rats were randomly divided into following groups： group control rats; group diabetic rats; group diabetic rats treated with amioguanidine（100mg/kg/d）; group diabetic rats treated with baicalin （150mg/kg/d）; These rats were induced hyperglycemia by intraperitoneal injection of streptozotocin 60mg/kg. In the end of 16 weeks treatment the rats were sacrificed and to measure aorta tissue nonenzymatic glycation,retina Bcl-2,Bax protein expression and to observe apoptosis by transmission electron microscope. Results （1） Comparing to control group ,the diabetic rat aorta tissue nonenzymatic glycation was apparently higher （P〈0.01）.After 16 weeks treatment, nonenzymatic glycation in group treated with amioguanidine and group treated with baicalin was significantly decreased than that of diabetic group （P〈0.01）. （2）The retina Bcl-2 protein expression in diabetic group were significantly decreased and Bax protein expression were significantly increased.After 16 weeks treatment of amioguanidine and baicalin ,the Bcl-2,Bax protein expression were significantly improved. （3）The retina apoptosis changes of diabetic group were observed in transmission electron microscope, and those morphology change was lessen in two treatment groups. Conclusion （1） By regulating Bcl-2 and Bax expression , nonenzymatic glycation increased the apoptosis ,then retinopathy was induced. （2）Nonenzymatic glycation inhibitors regular Bax,Bcl-2 expression to inhibit apoptosis ,then to delay the development of diabetic retinopathy. （3）Similar to the effect of typical nonenzymatic glycation inhihitors amioguanidinc, baicalin is to be worth to clinical application, with its less cost and fewer side effects.