灵芝多糖对妊娠期糖尿病大鼠肝脏损伤的保护作用

Protective effect of Ganoderma lucidum polysaccharides on liver injury

目的探讨灵芝多糖对妊娠期糖尿病(GDM)大鼠肝脏损伤的保护作用及肝组织磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖-6-磷酸酶(G-6-Pase)表达的影响。方法雌性大鼠经高脂高糖喂养8周后与雄鼠合笼制备孕鼠,妊娠5 d后,腹腔注射链脲佐菌素(STZ)诱导制备GDM大鼠模型,将成功建立的GDM大鼠随机分为模型组、阳性对照组及实验组,各15只;并取15只同批妊娠5 d大鼠作为空白组。实验组大鼠灌胃灵芝多糖400 mg·kg^-1·d^-1;阳性对照组灌胃盐酸二甲双胍200 mg·kg^-1·d^-1;空白组与模型组大鼠灌胃等量生理盐水,连续干预2周。用全自动生化分析仪检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)和碱性磷酸酶(ALP)活性;用蛋白质免疫印迹法检测大鼠肝组织PEPCK、G-6-Pase蛋白表达。结果空白组、模型组、阳性对照组及实验组大鼠血清GPT活性分别为(48.23±8.17),(103.52±17.39),(62.33±12.47),(74.81±15.84)U·L^-1;GOT活性分别为(106.38±25.12),(982.43±102.37),(569.33±71.24),(672.51±92.46)U·L^-1;ALP活性分别为(118.66±11.97),(164.86±13.56),(129.44±6.02),(140.65±8.11)U·L^-1;肝组织PEPCK蛋白相对表达量分别为0.14±0.06,0.81±0.13,0.26±0.07,0.49±0.11;G-6-Pase蛋白相对表达量分别为0.09±0.03,0.79±0.12,0.19±0.06,0.38±0.14。上述指标,模型组与空白组比较,差异均有统计学意义(均P<0.05);阳性对照组、实验组与模型组比较,差异均有统计学意义(均P<0.05)。结论灵芝多糖可有效降低GDM大鼠血糖水平,改善胰岛素抵抗与肝功能指标水平,从而保护肝脏,其作用机制可能与下调肝组织中PEPCK、G-6-Pase蛋白表达相关。

Objective To investigate the protective effect of Ganoderma lucidum polysaccharides on liver injury and the expression of phosphoenolpyruvate carboxykinase(PEPCK)and glucose-6-Pase in liver tissues of gestational diabetes mellitus(GDM)rats.Methods Female rats were fed with high-fat and high-sugar diet for 8 weeks and then caged with male rats to prepare pregnant rats,after 5 days of pregnancy,GDM rat models were induced by intraperitoneal injection of streptozotocin(STZ),the successfully established GDM rats were randomly assigned to the model group,the active control group and the test group,with 15 rats in each group;Fifteen rats of the same pregnancy for 5 days were selected as the blank group.Ganoderma lucidum polysaccharide(400 mg·kg^-1·d^-1)was orally administered to rats in the test group;metformin hydrochloride(200 mg·kg^-1·d^-1)was orally administered to the positive control group;the rats in the Blank group and the model group were intragastrically administered the same amount of normal saline,and the intervention was continued for 2 weeks.The activity of glutamic-pyruvic transaminase(GPT)and glutamic-oxaloacetic transaminase(GOT)and alkaline phosphatase(ALP)in serum were detected by the fully automatic biochemical analyzer;Western blotting was used to detect the expression of PEPCK and G-6-Pase protein in rat liver tissues.Results The serum GPT activities in the blank group,the model group,the active control group and the test group were(48.23±8.17),(103.52±17.39),(62.33±12.47),(74.81±15.84)U·L^-1;GOT activities were(106.38±25.12),(982.43±102.37),(569.33±71.24),(672.51±92.46)U·L^-1;ALP activities were(118.66±11.97),(164.86±13.56),(129.44±6.02),(140.65±8.11)U·L^-1;The relative expression of PEPCK protein in liver tissues were 0.14±0.06,0.81±0.13,0.26±0.07,0.49±0.11;the relative expression of G-6-Pase protein were 0.09±0.03,0.79±0.12,0.19±0.06,0.38±0.14.Compared between model group and blank group,the differences of the factors were significant(all P<0.05);Compared between acitive control group,test group and model group,the differences of the factors were significant(all P<0.05).Conclusion Ganoderma lucidum polysaccharide can effectively reduce blood glucose levels in GDM rats,improve insulin resistance and liver function indexes,thus protect the liver,and the mechanism may be associated with the down-regulation of PEPCK and G-6-Pase protein expression in liver tissues.