川芎嗪对糖尿病大鼠组织非酶糖化和视网膜细胞凋亡的影响

目的：观察非酶糖化与糖尿病视网膜细胞凋亡的关系以及非酶糖化抑制剂氨基胍和具有非酶糖化抑制作用的川芎嗪对糖尿病视网膜病变的治疗作用。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-1· d-1）治疗组、糖尿病川芎嗪（150mg· kg-1· d-1）治疗组，除正常对照组，其余实验组分别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bcl-2，bax的表达，电镜观察细胞凋亡的形态学变化。结果①治疗16周结束，糖尿病各实验组大鼠体重低于正常对照组（P＜0．01），糖尿病各实验组间体重比较差异无统计学意义（P＞0．05）。②糖尿病各实验组血糖水平高于正常对照组（P＜0．01），氨基胍治疗组与川芎嗪治疗组血糖与治疗前比较，差异无统计学意义（P＞0．05）。③与正常对照组相比，糖尿病组非酶糖化明显升高（P＜0．01），氨基胍治疗组、川芎嗪治疗组较糖尿病组非酶糖化降低（P＜0．01）。④透射电镜下见糖尿病组大鼠视网膜神经节细胞呈典型的凋亡形态学改变，氨基胍治疗组、川芎嗪治疗组大鼠细胞凋亡改变减轻。结论非酶糖化抑制剂氨基胍、川芎嗪抑制非酶糖化、抑制细胞凋亡，延缓糖尿病视网膜病变发展。

The Effect of Amioguanidine and Ligustrazine on Tissue Nonenzymatic Glycation and Retina Apoptosis in Diabetic Rats

Objective By studying the relationship between nonenzymatic glycation ,apoptosis relative protein bcl-2,bax and dia-betic retinopathy ,to explore the treatment effect of nonenzymatic glycation inhibitors on diabetic retinopathy .Methods Forty male Wistar rats were randomly divided into the following groups：group control rats,group diabetic rats,group diabetic rats treated with amioguanidine （100mg · kg -1· d-1）,group diabetic rats treated with ligustrazine（150mg· kg-1· d-1）.These rats were induced hyperglycemia by intraperitoneal injection of streptozotocin 60mg/kg.At the end of treatment the rats were sacrificed to measure tissue nonenzymatic glycation ,bcl-2,bax pro-tein expression ,and to observe retina pathology and apoptosis .Results ①Comparing to control group ,the diabetic rat retina tissue nonenzy-matic glycation was apparently higher （P〈0.01）.②After 16 weeks treatment,nonenzymatic glycation in group treated with amioguanidine and group treated with ligustrazine was more significantly decreased than that of diabetic group （P〈0.01）.③The retina bcl-2 protein expres-sion in diabetic group were significantly decreased and Bax protein expression were significantly increased .After 16 weeks treatment of ami-oguanidine and ligustrazine ,the bcl-2 protein expression were significantly increased and bax protein expression were decreased .④The retina apoptosis changes of diabetic group were observed in transmission electron microscope ,and those morphology changes were lessen in two treat-ment groups.Conclusion ①By regulating bcl-2 and Bax expression ,nonenzymatic glycation increase the apoptosis to induce diabetic reti-nopathy .②Nonenzymatic glycation inhibitors regulate bax ,bcl-2 expression to inhibit apoptosis ,then to improve diabetic retina structure and function,and to delay the development of diabetic retinopathy .