吴 萌,吕 平,杨亚丽,李 巍,尹志勇,李 妍.烟酰胺核糖抑制小鼠糖尿病心肌病损伤的作用研究[J].现代生物医学进展英文版,2018,(3):423-427. |
烟酰胺核糖抑制小鼠糖尿病心肌病损伤的作用研究 |
Nicotinamide Riboside Attenuates Injury of Mouse Diabetic Cardiomyopathy and Possible Mechanism |
Received:May 28, 2017 Revised:June 23, 2017 |
DOI:10.13241/j.cnki.pmb.2018.03.005 |
中文关键词: 烟酰胺核糖 糖尿病心肌病 Sirt3 |
英文关键词: Nicotinamide riboside Diabetic cardiomyopathy Sirt3 |
基金项目:国家自然科学基金项目(81570252;81500195) |
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中文摘要: |
摘要 目的:探讨烟酰胺核糖(Nicotinamide riboside,NR)在糖尿病小鼠心肌病中的保护作用及其可能机制。方法:80只20~25 g雄性昆明小鼠随机分为对照组(n=20)、对照+NR组(n=20)、DCM组(n=20)、DCM+NR组(n=20)。链脲佐菌素(STZ)对小鼠腹腔注射诱导1型糖尿病,最后1次STZ注射完成后第5日,血糖仪检测小鼠尾静脉血葡萄糖水平,三次测量随机血糖均≥16.7 mmol/L的视为糖尿病小鼠。糖尿病小鼠继续喂养12w,小动物超声检测提示心功能减退的为DCM小鼠。从中随机选出20只,腹腔注射NR(1000 mg/kg),2次/日,连续2w,为DCM+NR组。采用小动物超声分别检测各组小鼠心功能,天狼星红染色观察各组小鼠的心肌纤维化程度,Western blot检测心肌组织Atg7、Beclin-1、P62、Sirt3的表达。结果:与DCM组相比,DCM+NR组左室射血分数[LVEF(%)]增加(P<0.01),为DCM组的2.12倍;左室短轴缩短率[LVFS(%)]增加(P<0.01),为DCM组的2.79倍;左心室收缩末期容积(LV Vol;s)降低(P<0.01),为DCM组的0.25;左心室舒张末期容积(LV Vol;d)降低(P<0.01)、为DCM组的0.66;心肌纤维化程度减少(P<0.01)、为DCM组的0.63;Atg7、Beclin-1、Sirt3表达增加(P<0.05),P62表达降低(P<0.01)。结论:NR能够减轻小鼠DCM心肌间质纤维化、改善心功能,Sirt3通路的激活可能参与了NR减轻小鼠DCM损伤的保护作用。 |
英文摘要: |
ABSTRACT Objective: To observe the protective effects and mechanism of Nicotinamide ribosidefor the injury of mouse diabetic cardiomyopathy. Methods: Eighty male Kunming mice (20~25 g) were randomly divided into four groups: control group (n=20), con- trol+NR group (n=20), diabetic cardiomyopathy (DCM) group (n=20) and DCM+ NR group (n=20). The mice were intraperitoneally in- jected with streptozotocin to induce type 1 diabetes. Mice with random blood glucose≥16.7 mmol/L were considered as diabetic mice and they were fed for 12 weeks. Mice with impaired cardiac functions evidenced byechocardiography were chosen as diabetic cardiomy- opathy mice and twenty of them were randomly chosen to receive intraperitoneal injection of NR (1000 mg/kg, twice daily) for 2 consec- utive weeks, grouped as DCM+NR group. Cardiac functions were evaluated by echocardiography. Myocardial interstitial fibrosis was evaluated by Sirius red staining. Expressions of Atg7, Beclin-1, P62, Sirt3 were detected by Western blotting. Results: Compared with those in DCM group, the values of LVEF and LVFS in DCM+NR group were increased: the values of LVEF with 2.12 times to the DCM group, the values LVFS with 2.79 times to the DCM group.While the values of LV Vol; s and LV Vol;d were decreased (P<0.01): the LV Vol; s with 0.25 times to the DCM group, theLVVol; dwith 0.63 times to the DCM groupCompared with those in DCM group, myocar- dial interstitial fibrosis was reduced in DCM+NR group (P<0.01) and expressions of Atg7, Beclin-1, Sirt3 were increased (P<0.01, P<0.01 and P<0.05, respectively) and expressions of P62 was decreased (P<0.05 and P<0.01). Conclusion: Nicotinamide riboside could reduce myocardial interstitial fibrosis and improve cardiac function in diabetic cardiomyopathy mice. These protective effects of NR may possi- bly be through the activation of Sirt3 signal pathway. |
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