高糖高脂联合低剂量链脲佐菌素对版纳微型猪肝脏损伤和蛋白激酶B表达的影响  

Effect of high sucrose / high fat diet and streptozotocin on liver damage and expression of protein kinase B in Chinese Banna minipigs

作　　者：肖国华[1] 王月婷[2] 张素君[3] 余坚[3] 张亚丽[2] 王宗保[2] 

机构地区：[1]南华大学医学院,湖南衡阳421001 [2]南华大学药学与生物科学学院,湖南衡阳421001 [3]南华大学实验动物部,湖南衡阳421001

出　　处：《中国实验动物学报》2015年第1期63-68,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：湖南省科技厅重点科研项目(2012TT1001);湖南省与衡阳市联合基金项目(13JJ8012);湖南省科技厅项目(2013TT2006)

摘　　要：目的观察高糖高脂联合低剂量链脲佐菌素(streptozotocin,STZ)对版纳微型猪糖、脂代谢紊乱、肝组织病理改变及其蛋白激酶B(protein kinase B,PKB)磷酸化的影响,并探讨其机制。方法高糖高脂联合低剂量STZ诱导云南版纳微型猪2型糖尿病模型,每月末测定血糖、血脂、胰岛素,HE、PAS和苏丹Ⅳ染色观察肝脏显微结构。12个月末处死动物,real time-PCR和Western blotting检测肝组织PKB mRNA和总蛋白表达及PKB丝氨酸473(PKB-Ser473)的磷酸化水平。结果喂养12月后,与正常对照组比较,模型组显示高血糖、血脂障碍及胰岛素缺乏(P<0.05)。肝脏脂肪病变,肝糖原合成显著减少;PKB mRNA及蛋白表达增高(P<0.05),但PKB磷酸化降低(P<0.05)。结论高糖高脂联合STZ可诱导版纳微型猪发生胰岛素抵抗、糖尿病,促进肝脏脂质蓄积,抑制糖原合成,可能与信号分子PKB抑制有关。Objective To observe the effect of high sucrose/high fat diet and streptozotocin （STZ） on glucose and lipid metabolism, liver histology and protein kinase B （PKB） phasphorylation in Chinese Banna miniature pigs, and to in- vestigate its molecular mechanism. Methods Eight healthy 2-month old male Banna minipigs were randomly divided into control and diabetes groups, 4 pigs in each group. Diabetic minipigs were induced by high sucrose/high fat diet and STZ and the levels of fasting blood glucose, insulin, total cholesterol, triglycerides were measured per month for 12 months. At the end of 12th month, the minipigs were sacrificed and liver histology was examined using HE staining and the hepatic lipid accumulation was observed using Sudan IV staining. Real-time PCR and Western blot were used to determine the expres- sion of PKB mRNA and protein, and the phosphorylation level of PKB-Ser473 in the liver tissue. Results At the end of 12th month, the minipigs of model group showed hyperglycemia, insulin deficiency and dyslipidemia compared with that of the control group （P 〈 0.05）. The fat degeneration was increased, and glycogen was decreased in the liver tissue of model group. High sucrose/high fat diet and STZ increased the PKB mRNA and protein expression, while decreased PKB phos- phorylation in the liver tissue （P 〈 0. 05 ）. Conclusions High sucrose/high fat diet and STZ can induce insulin resistance （IR） and diabetes mellitus, promote lipid and cholesterol accumulation, and inhibite hepatic glycogenogenesis, which may be related with inhibition of PKB phosphorylation.

关 键 词：链脲佐菌素 高糖高脂饲料 2型糖尿病 肝脏 蛋白激酶B 版纳微型猪 

分 类 号：Q95-33[生物学—动物学]