机构地区:[1]山东大学研究生院,济南250100 [2]济宁医学院附属医院内分泌科,山东济宁272029
出 处:《中国生物制品学杂志》2010年第9期957-960,共4页Chinese Journal of Biologicals
基 金:济宁市科技局计划课题(济科字[2008]50号)
摘 要:目的探讨α-硫辛酸对糖尿病大鼠血糖、血脂及肝脏内腺苷酸活化蛋白激酶(Adenosine monophosphate activated protein kinase,AMPK)α亚基(AMPKα)表达及活性的影响。方法应用高脂饮食联合腹腔单次注射小剂量的链脲佐菌素(STZ)复制2型糖尿病合并脂代谢紊乱的Wistar大鼠模型,再将模型大鼠随机分为糖尿病对照(DC)组和α-硫辛酸治疗(LA)组,并设正常对照(NC)组。NC组和DC组每只给予生理盐水2ml/d,LA组经腹腔注射α-硫辛酸60mg/kg·d,共4周。分别测定各组大鼠的体重、血糖、血脂、糖化血红蛋白(HbA1c)和肝脏内AMPKα及磷酸化AMPKα(pAMPKα)的表达水平。结果建模后、给药前及给药后,NC组大鼠血糖水平均显著低于DC和LA组(P<0.01),给药后,LA组显著低于DC组(P<0.05)。给药4周后,DC组大鼠甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)和HbA1c水平均显著高于NC组(P<0.01),而高密度脂蛋白(HDL)、肝脏内AMPKα及pAMPKα的表达水平均显著降低(P<0.05);LA组大鼠TG、TC、LDL和HbA1c水平均较DC组显著下降(P<0.05),而HDL、AMPKα及pAMPKα表达水平均显著升高(P<0.05);DC组肝脏内AMPKα表达较NC组明显下降(P<0.05),LA组无明显变化(P>0.05)。结论α-硫辛酸可以通过调节肝脏内AMPKα的表达水平,进而改善糖尿病状态下的"糖脂毒性"。Objective To investigate the effect of α-lipoic acid on blood glucose,blood fat as well as expression and activity of adenosine monophosphate activated protein kinase subunit α(AMPKα)in the liver of diabetic rats.Methods Wistar rat model of diabetes type 2 complicated with fat metabolic disorder was copied by high fat diet combined with a single injection i.p.with streptozotocin(STZ)at low dosage.The model rats were randomly divided into diabetes control(DC)and α-lipoic acid(LA)groups,setting healthy rats as normal control(NC)group.Each rat in NC and DC groups were injected i.p.with 2 ml of physiological saline,while that in LA group with α-lipoic acid at a dosage of 60 mg /kg bodyweight,once a day for 4 weeks.The bodyweight,blood glucose,blood fat,HbAlc as well as expression levels of AMPKα and phophorylated AMPKα(pAMPKα)in liver of rats in various groups were determined.Results The blood glucose levels of rats in NC group before and after administration were significantly lower than those in DC and LA groups(P 0.01).However,the blood glucose level of rats in LA group after administration was significantly lower than that in DC group(P 0.05).Four weeks after administration,the TG,TC,LDL and HbAlc levels of rats in DC group were significantly higher(P 0.01),while the HDL as well as AMPKα and pAMPKα levels were significantly lower than those in NC group(P 0.01).Compared with those in DC group,the TG,TC,LDL and HbAlc levels of rats in LA group decreased significantly(P 0.05),while HDL,AMPKα and pAMPKα levels increased significantly(P 0.05).The expression level of AMPKα decreased significantly in DC group as compared with that in NC group,while showed no significant change in LA group(P 0.05).Conclusion α-Lipoic acid may decrease the"glucolipid toxicity"in the state of diabetes by regulating the expression level of AMPKα in liver.
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