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作 者:曹琼丹 杨育红[1] 于胜男[1] 鲁美丽[1] 张素萍[1] 韩镕徽 胡进[1]
机构地区:[1]辽宁医学院心脑血管药物研究重点实验室,辽宁锦州121001
出 处:《中国药理学通报》2015年第8期1096-1101,共6页Chinese Pharmacological Bulletin
基 金:国家自然科学基金资助项目(No 81374008)
摘 要: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,RTPCR检测心肌组织中PGC-1α和NRF-1 m RNA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LVEDP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m RNA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。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 50 SD rats at 6 weeks of age were assigned to 5groups, 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 ofSTZ (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 nd 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.
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