摘要
目的研究葛根素(puerarin,PR)通过SIRT1/PGC-1α信号通路对2型糖尿病(type 2 diabetes mellitus,T2DM)小鼠胰腺线粒体氧化应激损伤的作用。方法以链脲佐菌素与高脂高糖饮食构建T2DM小鼠模型。将模型小鼠随机分成模型、二甲双胍(40 mg·kg-1·d-1)、PR(20、40、80 mg·kg-1·d-1)组,连续灌胃给药8周,每日1次。末次给药后,血糖仪检测FBG。HE染色观察胰腺病理学变化。试剂盒检测法检测胰腺的·OH、ROS、ATP含量、Mn-SOD、CAT、ComplexⅠ、Ⅲ、Ⅳ的活性。Western blot法检测胰腺的NRF1、TFAM、Mfn1、OPA1的表达。RT-PCR法检测SIRT1、PGC-1α mRNA在胰腺中的表达。结果与模型组相比,PR干预组的FBG含量下降(P <0.05),胰岛形态好转,胰腺中CAT、Mn-SOD、ComplexⅠ、Ⅲ、Ⅳ活性增加,ATP含量增多,·OH、ROS的含量减少(P <0.05)。NRF1、TFAM、Mfn1、OPA1蛋白及SIRT1、PGC-1αmR NA的表达升高(P <0.05)。结论PR可使T2DM小鼠FBG及ROS下降,其作用机理可能为PR调控SIRT1/PGC-1α信号通路,达到对胰腺组织的保护作用。
Aim To investigate the effect of puerarin(PR)on mitochondrial oxidative and pancreas damage in type 2 diabetic mellitus(T2DM)mice by targeting SIRT1/PGC-1αsignaling pathway.Methods The mice were tail intravenously injected with streptozotocin(STZ)and fed with a high fat and high glucose diet to induce T2DM model.The model mice were randomly divided into model control group,metformin(40 mg·kg^-1·d^-1)group and PR groups(20 mg·kg^-1·d^-1,40 mg·kg^-1·d^-1,80 mg·kg^-1·d^-1).The mice were treated with drugs respectively via stomach gavage daily for 8 weeks.After last administration,the fasting blood glucose(FBG)was measured by blood glucose meter.HE staining was used to observe the pathological changes of pancreas.The levels of·OH,ROS and ATP,activities of Mn-SODand CAT in pancreatic tissues,and the activities of complex I,III,IV in pancreas mitochondria were detected by commercial kits.The expressions of mitochondrial biosynthesis factors NRF1,TFAM and mitochondrial fusion factors Mfn1,OPA1 were analyzed by Western blot method.The mRNA levels of SIRT1 and PGC-1αin pancreas were determined by RT-PCR.Results Compared with model control,the FBG levels in PR groups significantly decreased(P<0.05).The islet morphology and atrophy were alleviated.The activities of CAT,Mn-SOD,complex I,III and IV in pancreas mitochondria were obviously enhanced(P<0.05),as well as ATP level,whereas the·OH and ROS contents decreased(P<0.05).Moreover,the protein levels of NRF1,TFAM,Mfn1 and OPA1 were elevated,as well as the mRNA levels of SIRT1,PGC-1α(P<0.05).Conclusions The mechanism of PR on reducing FBG and ROS in T2DM may be related to the modulation on SIRT1/PGC-1αsignaling pathway,achieving protective effects on pancreatic tissues.
作者
徐小惠
黄英华
陈铭
黄燕军
梁韬
XU Xiao-hui;HUANG Ying-hua;CHEN Ming;HUANG Yan-jun;LIANG Tao(Dept of Pharmacy,Affiliated Tumor Hospital of Guangxi Medical University,Nanning 530021,China;Dept of Pharmacy,College&Hospital of Stomatology,Guangxi Medical University,Nanning 530021,China;Pharmaceutical College,Guangxi Medical University,Nanning 530021,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第10期1373-1379,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81960671)
广西自然科学基金资助项目(No 2018GXNSFBA281037,2018GXNSFB A281096)。
