[1]梅稳,向光大,卢俊颜,等.GDF11对ApoE-/-糖尿病小鼠内皮依赖性 血管舒张功能的作用[J].国际内分泌代谢杂志,2016,36(02):101-106.[doi:10.3760/cma.j.issn.1673-4157.2016.02.007]
 Mei Wen*,Xiang Guangda,Lu Junyan,et al.Effects of GDF11 on endothelium-dependent vasodiation function of aorta in ApoE-/- diabetic mice[J].International Journal of Endocrinology and Metabolism,2016,36(02):101-106.[doi:10.3760/cma.j.issn.1673-4157.2016.02.007]
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GDF11对ApoE-/-糖尿病小鼠内皮依赖性 血管舒张功能的作用()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
36
期数:
2016年02期
页码:
101-106
栏目:
论著
出版日期:
2016-03-20

文章信息/Info

Title:
Effects of GDF11 on endothelium-dependent vasodiation function of aorta in ApoE-/- diabetic mice
作者:
梅稳向光大卢俊颜李欢向林董靖
510515 广州,南方医科大学附属武汉临床学院(梅稳,向光大,卢俊颜,李欢); 430070 武汉,广州 军区武汉总医院内分泌科(向光大,向林,董靖)
Author(s):
Mei Wen* Xiang Guangda Lu Junyan Li HuanXiang Lin Dong Jing.
*Wuhan Clinical Institute Affiliated to Southern Medical University, Guangzhou 510515, China
关键词:
生长分化因子11 2型糖尿病 内皮依赖性血管舒张 一氧化氮
Keywords:
Growth differentiation factor 11 Type 2 diabetes mellitus Endothelium-dependent vasodilation Nitric oxide
DOI:
10.3760/cma.j.issn.1673-4157.2016.02.007
摘要:
目的 研究生长分化因子11(GDF11)对载脂蛋白 E 基因敲除(ApoE-/-)糖尿病小鼠胸主动脉内皮依赖性血管舒张功能的影响,探讨其可能的机制。方法 40只4周龄健康雄性ApoE-/-小鼠按随机数字法选择10只作为正常对照组(NC组),以正常饲料喂养,其余30只以高脂饲料喂养4周后,连续5 d腹腔注射链脲佐菌素(50 mg/kg)制备2型糖尿病模型。将造模成功小鼠共20只按随机数字法分为GDF11组(0.1 mg·kg-1·d-1腹腔注射,n=10)和糖尿病对照组(T2DM组,等量磷酸盐缓冲液腹腔注射,n=10)。干预4周后,检测各组空腹血糖、空腹胰岛素、HbA1c、GDF11浓度,并计算稳态模型评估-胰岛素敏感性指数(HOMA-ISI); 测定各组小鼠离体胸主动脉条的张力反应及主动脉一氧化氮含量,Western印迹检测主动脉内皮型一氧化氮合酶(eNOS)、磷酸化eNOS(P-eNOS)、Smad2/3、磷酸化Smad2/3(P-Smad2/3)水平。结果 与NC组相比,T2DM组空腹血糖、空腹胰岛素、HbA1c水平升高,GDF11浓度及HOMA-ISI降低,乙酰胆碱引起的内皮依赖性舒张反应降低; 与T2DM组相比,GDF11组上述指标均有改善(F=70.923~675.430,P均<0.01)。而硝普钠诱导的内皮非依赖性舒张反应各组间差异无统计学意义(P>0.05)。与NC组相比,T2DM组血管中一氧化氮含量、P-eNOS水平、磷酸化Smad2/3水平下降,GDF11组上述指标均有显著升高(F=40.120~148.060,P均<0.01)。 结论 GDF11通过促进一氧化氮生成,激活Smad2/3信号通路,改善ApoE-/-糖尿病小鼠内皮依赖性血管舒张功能。
Abstract:
Objective To explore the effects of growth differentiation factor 11(GDF11)on endothelium-dependent vasodilation function of aorta in apolipoprotein E-Null(ApoE-/-)diabetic mice and to investigate the mechanisms. Methods Ten of the 40 healthy male ApoE-/- mice at 4-week age were selected as normal control group according to random number method and received basic diet, whereas the other 30 mice were fed with high-fat diet for 4 weeks and then treated with streptozotocin intraperitoneal injection(50 mg/kg)for 5 days to induce type 2 diabetes mellitus(T2DM). Diabetes was successfully induced in twenty mice which were then randomly divided into GDF11 group(0.1 mg·kg-1·d-1 intraperitoneal injection, n=10)and T2DM control group(T2DM group, equivalent phosphate buffered saline, n=10)according to random number method. After 4 weeks of intervention, fasting plasma glucose, fasting plasma insulin, HbA1c and serum GDF11 were measured respectively. Homeostasis model assessment-insulin sensitive index(HOMA-ISI)was calculated. The relaxation response and nitric oxide levels were detected in isolated aorta of mice. Acetylcholine(Ach)-induced endothelium-dependent vasodilation and sodium nitroprusside(SNP)-induced endothelium-independent vasodilation were measured in aortas for estimating endothelial function. Endothelial nitric oxide synthase(eNOS), phosphorylated eNOS(P-eNOS)and Smad2/3, phosphorylated Smad2/3(P-Smad2/3)were measured by Western blotting in isolated aorta of mice. Results Compared with NC group, fasting plasma glucose, fasting plasma insulin, and HbA1c were significantly increased, meanwhile HOMA-ISI, serum GDF11 concentration and Ach-dependent relaxation response were significantly reduced in T2DM group; compared with T2DM group, all markers mentioned above were improved in GDF11 group(F=70.923-675.430, all P<0.01); whereas the SNP-independent relaxation were not different among three groups(P>0.05). Compared with NC group, nitric oxide, P-eNOS, P-Smad2/3 were significantly decreased in T2DM group, but indexes mentioned above were all increased in GDF11 group(F=40.120-148.060, all P<0.01).Conclusion GDF11 improves endothelium-dependent vasodilation function in ApoE-/- diabetic mice by enhancing nitric oxide synthesis and Smad2/3 signaling pathways.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81370896)
更新日期/Last Update: 2016-03-20