中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
8期
1096-1100,1101
,共6页
曹琼丹%杨育红%于胜男%鲁美丽%张素萍%韩镕徽%胡进
曹瓊丹%楊育紅%于勝男%魯美麗%張素萍%韓镕徽%鬍進
조경단%양육홍%우성남%로미려%장소평%한용휘%호진
黄芪甲苷%糖尿病心肌病%PGC-1α%NRF-1%线粒体%能量代谢
黃芪甲苷%糖尿病心肌病%PGC-1α%NRF-1%線粒體%能量代謝
황기갑감%당뇨병심기병%PGC-1α%NRF-1%선립체%능량대사
astragaloside IV%diabetic cardiomyopa-thy%PGC-1α%NRF-1%mitochondria%energy metabolism
目的:探讨黄芪甲苷( ASIV)对链脲佐菌素( STZ)诱导的糖尿病大鼠心肌细胞能量代谢及线粒体合成的影响。方法50只6周龄的SD大鼠,分为5组,每组10只,分别是空白组、模型组、ASIV 10、20、40 mg·kg-1组。除空白组,其余40只尾静脉注射STZ(35 mg·kg-1)建立Ⅰ型糖尿病心肌病模型。连续给药16周后,检测其左心室收缩压( LVSP)、左心室舒张期末压( LVEDP )、左心室最大上升/下降速率(± dp/dtmax ),苏木精-伊红( HE)染色观察心肌病理切片。ELISA检测心肌组织中 ATP、ADP、AMP 的含量。 Western blot法检测心肌组织中过氧化体增殖物激活型受体γ共激活因子1α( PGC-1α)和核呼吸因子( NRF-1)蛋白表达, RT-PCR检测心肌组织中PGC-1α和NRF-1 mRNA的表达。结果与空白组相比,模型组大鼠的 LVEDP 上升, LVSP、± dp/dtmax下降, ATP/ADP、ATP/AMP比值均下降。与模型组相比,黄芪甲苷低剂量组变化不明显,中、高剂量组 LV-EDP下降,LVSP、± dp/dtmax上升, ATP/ADP、ATP/AMP比值均上升, PGC-1α与 NRF-1的蛋白表达和 mRNA 表达均增加,有一定的剂量依赖性。结论黄芪甲苷通过提高PGC-1α和NRF-1的表达促进Ⅰ型糖尿病大鼠心肌细胞内线粒体的生物合成,提高能量代谢。
目的:探討黃芪甲苷( ASIV)對鏈脲佐菌素( STZ)誘導的糖尿病大鼠心肌細胞能量代謝及線粒體閤成的影響。方法50隻6週齡的SD大鼠,分為5組,每組10隻,分彆是空白組、模型組、ASIV 10、20、40 mg·kg-1組。除空白組,其餘40隻尾靜脈註射STZ(35 mg·kg-1)建立Ⅰ型糖尿病心肌病模型。連續給藥16週後,檢測其左心室收縮壓( LVSP)、左心室舒張期末壓( LVEDP )、左心室最大上升/下降速率(± dp/dtmax ),囌木精-伊紅( HE)染色觀察心肌病理切片。ELISA檢測心肌組織中 ATP、ADP、AMP 的含量。 Western blot法檢測心肌組織中過氧化體增殖物激活型受體γ共激活因子1α( PGC-1α)和覈呼吸因子( NRF-1)蛋白錶達, RT-PCR檢測心肌組織中PGC-1α和NRF-1 mRNA的錶達。結果與空白組相比,模型組大鼠的 LVEDP 上升, LVSP、± dp/dtmax下降, ATP/ADP、ATP/AMP比值均下降。與模型組相比,黃芪甲苷低劑量組變化不明顯,中、高劑量組 LV-EDP下降,LVSP、± dp/dtmax上升, ATP/ADP、ATP/AMP比值均上升, PGC-1α與 NRF-1的蛋白錶達和 mRNA 錶達均增加,有一定的劑量依賴性。結論黃芪甲苷通過提高PGC-1α和NRF-1的錶達促進Ⅰ型糖尿病大鼠心肌細胞內線粒體的生物閤成,提高能量代謝。
목적:탐토황기갑감( ASIV)대련뇨좌균소( STZ)유도적당뇨병대서심기세포능량대사급선립체합성적영향。방법50지6주령적SD대서,분위5조,매조10지,분별시공백조、모형조、ASIV 10、20、40 mg·kg-1조。제공백조,기여40지미정맥주사STZ(35 mg·kg-1)건립Ⅰ형당뇨병심기병모형。련속급약16주후,검측기좌심실수축압( LVSP)、좌심실서장기말압( LVEDP )、좌심실최대상승/하강속솔(± dp/dtmax ),소목정-이홍( HE)염색관찰심기병리절편。ELISA검측심기조직중 ATP、ADP、AMP 적함량。 Western blot법검측심기조직중과양화체증식물격활형수체γ공격활인자1α( PGC-1α)화핵호흡인자( NRF-1)단백표체, RT-PCR검측심기조직중PGC-1α화NRF-1 mRNA적표체。결과여공백조상비,모형조대서적 LVEDP 상승, LVSP、± dp/dtmax하강, ATP/ADP、ATP/AMP비치균하강。여모형조상비,황기갑감저제량조변화불명현,중、고제량조 LV-EDP하강,LVSP、± dp/dtmax상승, ATP/ADP、ATP/AMP비치균상승, PGC-1α여 NRF-1적단백표체화 mRNA 표체균증가,유일정적제량의뢰성。결론황기갑감통과제고PGC-1α화NRF-1적표체촉진Ⅰ형당뇨병대서심기세포내선립체적생물합성,제고능량대사。
Aim To investigate the effect of astragalo-side IV ( ASIV) on myocardial energy metabolism and mitochondrial biosynthesis in myocardial cells of dia-betic rats induced by streptozotocin ( STZ ) . Methods <br> 50 SD rats at 6 weeks of age were assigned to 5 groups,10 for each group:control group, model group, ASIV 10 mg·kg-1 ·d-1 group, ASIV 20 mg·kg-1 ·d-1 group, ASIV 40 mg·kg-1 ·d-1 group. Except the control group,the remaining 40 were used to estab-lish type 1 diabetes model by the tail vein injection of STZ (35 mg·kg-1 ) . At the end of 16 weeks of treat-ment, left ventricular systolic pressure ( LVSP ) , left ventricular diastolic final pressure ( LVEDP ) and left ventricular maximum rising/falling rate ( ± dp/dtmax ) were tested. Pathological section was observed by HE staining. ATP, ADP, AMP levels were detected by ELISA. The expressions of PGC-1α and NRF-1 protein were assessed by Western blot. The expressions of PGC-1α and NRF-1 mRNA were determined by RT-PCR. Results Compared with control group, model group markedly elevated LVEDP and decreased LVSP, ± dp/dtmax , ATP/AMP and ATP/ADP ratio. Com-pared with model group, low-dose ASIV group did not change significantly,middle-dose ASIV group and high-dose ASIV group obviously decreased LVEDP, and im-proved LVSP, ± dp/dtmax , ATP/ADP and ATP/AMP ratio. Meanwhile, the expressions of PGC-1α and NRF-1 protein and mRNA were increased in a dose-de-pendent manner. Conclusion ASIV could promote mitochondrial biosynthesis, improve energy metabolism in myocardial cells of type 1 diabetic rats by PGC-1αand NRF-1 .