栀子苷通过抑制细胞凋亡保护糖尿病大鼠胰岛细胞

Protective effects of geniposide on diabetes via inhibiting apoptosis in diabetic rats Islets

目的探索栀子苷(GEN)对糖尿病大鼠胰岛细胞的影响及相关机制。方法利用链脲佐菌素(STZ)制作大鼠糖尿病模型,50只SD大鼠随机分为5组,对照组,模型组,栀子苷10 mg/kg,栀子苷25 mg/kg,栀子苷50 mg/kg,每组10只,连续栀子苷灌胃用药1周后,对照组和模型组只给与等量生理盐水灌胃处理。检测大鼠空腹血糖值;利用Western blot法检测凋亡因子NF-κB以及凋亡蛋白Bax、Bcl-2表达;酶联免疫吸附(ELISA)法检测Caspase-3、Caspase-9活性。结果一周后,模型组血糖值显着高于对照组,而栀子苷组较模型组有明显降低(P<0.05);Western blot显示,模型组NF-κB和Bax表达显着高于对照组,而栀子苷组则明显抑制NF-κB和Bax表达,并呈剂量依赖效应(P<0.05),相反,模型组中Bcl-2表达则显着低于对照组,而栀子苷组则显着高于模型组(P<0.05);ELISA显示,模型组Caspase-3、Caspase-9活性显着高于对照组,而栀子苷组则明显抑制Caspase-3、Caspase-9活性,并呈剂量依赖效应(P<0.05)。结论栀子苷对糖尿病大鼠模型具有降糖作用,可能是通过抑制NF-κB和Bax,提高Bcl-2表达,同时还可能抑制Caspase-3和Caspase-9蛋白酶活性,从而减轻了胰岛细胞的凋亡来发挥作用。

Objective To explore 出 e protective effects of geniposide on diabetes via inhibiting apoptosis in diabetic rats Islets tential mechanism. Methods The model diabetic rats were made using streptozotocin. 50 SD rats were divided into 5 groups, the control group, model group, Geniposide 10 mg/kg, Geniposide 25 mg/kg and Geniposide 50 mg/kg. The fasting blood glucose level was detected 1 week later, and the relative protein expression of NF - kB , Bax and Bcl - 2 were also detected by western blot. Meanwhile, the activities of Caspase - 3 and Caspase - 9 were detected by elisa. Results The blood glucose level in model group was significantly higher than that in control group, while, ge-niposide markedly suppressed the blood glucose level compared with the model group （ P 〈0. 05） . Western blot showed that the relative expres-sion of NF - kB and Bax were effectively higher in the model group compared with the control group, while geniposide markedly suppressed the ex-pression of NF - kB and Bax （ P 〈 0.05） . Meanwhile, geniposide effectively increased the expression of Bcl - 2 （ P 〈 0.05 ） . Elisa showed that the activities of Caspase - 3 and Caspase - 9 were significantly higher in the model group compared with the control group, while, geniposide markedly suppressed the activities of Caspase - 3 and Caspase - 9 （ P 〈 0.05）. Conclusion Geniposide could protect the diabetes probably, may be through the inhibition of NF - kB and Bax, increased Bcl - 2 expression, but also inhibit Caspase - 3 and Caspase - 9 protease activity, thereby reducing the islet cell apoptosis to play a role.