罗布麻叶水提取物对链脲佐菌素致糖尿病小鼠的治疗作用及对肠道GLP-1蛋白表达的影响

Therapeutic effect of water extract of Apocynum venetum leaves on STZ induced diabetic mice and its effect on intestinal GLP-1 protein expression

目的探讨罗布麻叶水提取物(WEAVL)对链脲佐菌素(STZ)致糖尿病模型小鼠的治疗作用。方法随机将ICR小鼠分为对照组和WEAVL(2.34 g/kg)组,每天ig给药1次,连续30 d,检测空腹血糖和体质量。ICR小鼠按200 mg/kg ip2%STZ溶液制备糖尿病模型,造模成功的小鼠按血糖值随机分为模型组、盐酸二甲双胍(阳性药,130 mg/kg)组和WEAVL低、中、高剂量(0.58、1.17、2.34 g/kg)组,另设对照组,连续给药30 d,测定体质量、空腹血糖、糖耐量及血糖曲线下面积(AUC);称取肝、肾质量,计算脏器系数;取胰腺组织进行HE染色、组织病理学检查;Western blotting检测肠道组织胰高血糖素样肽-1(GLP-1)蛋白的表达水平。结果与对照组比较,单纯给予WEAVL对正常动物空腹血糖无明显影响,可显著降低小鼠体质量(P<0.01)。与对照组比较,模型组小鼠血糖显著升高(P<0.01),各组小鼠体质量均显著降低(P<0.01);与模型组比较,WEAVL高剂量组给药第2~4周体质量显著降低(P<0.05、0.01),3个剂量组2 h血糖、血糖AUC均显著降低(P<0.01),高剂量组肝脏系数显著降低(P<0.05)、肾脏系数显著升高(P<0.05),中、高剂量组动物胰岛细胞空泡变性例数减少,中、高剂量组肠道组织GLP-1蛋白的表达显著上调(P<0.05)。结论WEAVL对STZ致糖尿病小鼠有一定治疗作用,其作用机制可能与上调肠道组织中GLP-1的表达有关。

Objective To explore the therapeutic effects of water extract of Apocynum venetum leaves(WEAVL)on STZ-induced diabetic mice model.Methods ICR mice were randomly divided into control group and WEAVL(2.34 g/kg)group.The WEAVL group was given intragastric administration once a day for 30 days,and body mass and FPG was detected.ICR mice were modeled by intraperitoneal injection of 2% STZ solution at 200 mg/kg and 10 mL/kg.The successful models were randomly divided into model group,positive drug group(metformin 130 mg/kg),WEAVL low,medium and high dose(0.58,1.17 and 2.34 g/kg)group according to blood glucose value.A control group was set up with normal group.After continuous administration for 30 days,the body weight,FPG,OGTT and the area under the curve(AUC)of blood glucose were measured.The liver and kidney was weighed and the organ coefficients were calculated.Pancreatic tissues were HE stained for histopathological examination,Western blotting was used to evaluate the GLP-1 expression in ileum tissue of mice.Results Compared with control group,WEAVL only had no significant effect on FPG in normal animals,and the weight of mice decreased(P<0.01).Compared with the control group,the blood glucose of the model group was increased significantly(P<0.01),and the body weight of the mice in each group was significantly reduced(P<0.01);compared with model group,the body weight of the WEAVL high-dose group was significantly reduced(P<0.05 and 0.01),the two-hour blood glucose and the AUC of blood glucose of the positive drug group and the three dose groups of WEAVL were significantly reduced(P<0.01),the liver body coefficient of the WEAVL high dose group were significantly reduced(P<0.05),and the kidney body coefficient was obvious elevated(P<0.05),the number of cases of vacuolar degeneration in islet cell in the WEAVL middle and high dose groups was less than that in the model group,WEAVL significantly up-regulated the protein expression of GLP-1 in ileum tissue(P<0.05).Conclusions WEAVL has a certain therapeutic effect on STZ-induced diabetic mice,which may be related to the regulation of GLP-1 activation.