五子降糖方对2型糖尿病模型大鼠肝组织糖原及AKT/GSK-3β信号通路的影响

Influences of Wuzi Jiangtang Fang on hepatic glycogen and AKT/GSK-3β signal pathway in rat model of type 2 diabetes

目的观察五子降糖方对2型糖尿病模型大鼠肝组织糖原及丝氨酸-苏氨酸激酶(AKT)/糖原合成酶激酶-3β(GSK-3β)信号通路的影响,初步探讨其改善糖代谢的分子机制。方法高脂饮食喂养联合腹腔注射小剂量链脲佐菌素建立2型糖尿病大鼠模型,大鼠随机分为模型组、二甲双胍组、五子降糖方低、中、高剂量组(给予折合生药剂量分别为3.5、7.0、14.0 g/kg),另设正常组。正常组及模型组灌胃纯净水,其他各组大鼠分别灌胃相应的药物,干预6周。6周后处死大鼠,测定肝组织中糖原的含量,AKT、GSK-3β的蛋白表达量。结果与正常组比较,模型组大鼠空腹和餐后2 h血糖升高,肝脏组织糖原含量降低、AKT蛋白含量及其磷酸化水平降低、GSK-3β蛋白含量增加而其磷酸化水平降低(P<0.05);与模型组比较,五子降糖方各组大鼠空腹及餐后2 h血糖降低,肝脏组织糖原含量增加、AKT蛋白含量及其磷酸化水平升高、GSK-3β蛋白含量降低且其磷酸化水平升高(P<0.05)。结论五子降糖方可改善2型糖尿病模型大鼠糖代谢、增加肝脏糖原含量,其作用机制可能与提高肝脏AKT及GSK-3β丝氨酸位点磷酸化水平有关。

Objective To observe the influences of Wuzi Jiangtang Fang on hepatic glycogen and AKT/ glycogen synthase kinase-315 （ GSK-315） signal pathway in rat model of type 2 diabetes, and to explore its molecular mechanism in improving glucose metabolism. Methods The rat model of type 2 diabetes was established by feeding high fat diet combining intrapreitoneal injection of low-dose streptozotocin （ STZ）, and then all rats were divided into model group, metformin group, and low-dose, mid-dose and high-dose Wuzi Jiangtang Fang groups （low-dose group, mid-dose group and high-dose group）. The doses giving the rats in low-dose group, mid-dose group and high-dose group were 3.5 g/kg, 7.0 g/kg and 14.0 g/kg respectively. And a normal group was set up. The normal group and model group were intragastrically given purified water, and other groups were given corresponding drugs for 6 w. The rats were killed after6 w. The content of glycogen in liver tissues and the expressions of AKT and GSK-3β were detected. Results The levels of fasting blood glucose （FBG） and 2-h postprandial blood glucose （2-h PBG） increased, content of hepatic glycogen decreased, content of AKT decreased, AKT phosphorylation level decreased, content of GSK-313 increased, and GSK-3β phosphorylation level decreased in model group compared with normal group （P 〈 0.05）. The levels of FBG and 2-h PBG decreased, content of hepatic glycogen increased, content of AKT increased, AKT phosphorylation level increased, content of GSK-3β decreased, and GSK-3β phosphorylation level increased in Wuzi Jiangtang Fang group compared with model group （P 〈 0.05 ）. Conclusion Wuzi Jiangtang Fang can ameliorate glucose metabolism and increase the content of hepatic glycogen in rat model of type 2 diabetes, which may be related to increasing phosphorylation levels of AKT and GSK-3β.