利拉鲁肽对大鼠压力负荷型慢性心衰的保护作用
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Liraglutide protects pressure-overload rat heart from failure
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    摘要:

    目的 研究利拉鲁肽对压力负荷型慢性心衰大鼠心脏功能的作用及其机制。方法 30只SD大鼠随机分成假手术组、心衰组、利拉鲁肽组,每组10只大鼠。心衰组、利拉鲁肽组采用腹主动脉缩窄法制备模型,假手术组只穿线不缩窄。利拉鲁肽组术后12周给予利拉鲁肽皮下注射,2 mg/kg·d,共30 d。假手术组和心衰组给予同等剂量的生理盐水。给药30 d后给大鼠称重,并使用压力容积系统来检测血流动力学指标,同时对大鼠的各个器官称重。将大鼠麻醉后,腹主动脉抽血离心后取血清,按试剂盒方法测定超氧化物歧化酶(SOD)、B型钠尿肽(BNP)、丙二醛(MDA)。结果 心脏称重显示,利拉鲁肽组的心脏重量明显低于心衰组(P<0.05)。压力容积系统检测血流动力学显示,相比于假手术组,利拉鲁肽组大鼠的Ves、Ved、Pmax、Pes、Ped值均有明显降低(P<0.05),dP/dt max、-dP/dt min、EF和PowMax值则明显增加(P<0.05)。和心衰组相比,利拉鲁肽组大鼠血清中的SOD值明显增加(P<0.05),BNP值则明显降低(P<0.05)。结论 利拉鲁肽可以改善心衰大鼠左心室的收缩和舒张功能,减轻心肌细胞的损伤,其机制可能与抗氧化作用相关。

    Abstract:

    Objective To explore the effect of liraglutide on pressure-overload chronic heart failure in rats and related mechanisms. Methods Totally 30 SD rats were randomly divided into sham operation group, heart failure group and liraglutide group.The animals were anaesthetized and a Millar pressure volume conductance catheter SPR-838) was inserted through right carotid artery into LV to measure pressure-volume (P-V) loop.Body and organ weight were measured. After the end of intervention, the rats were anesthetized, and abdominal aortic blood taken from the upper serum after centrifugation. Kit method was used to measure superoxide dismutase (SOD), brain natriuretic peptide (BNP), malondialdehyde (MDA).Results Compared with those of the sham operation group, there was a increase in absolute heart weight and (P<0.05). During the P-V loop analyses, We found that left ventricular (LV) end-systolic volume, end-diastolic volume, end-systolic pressure, end-diastolic pressure and maximum pressure were all remarkablely lower in liraglutide group than HF group in rats (P<0.05). Peak rate of pressure rise (dP/dt max), peak rate of pressure decline (-dP/dt min), ejection fraction and Maximum Power were increased in liraglutide group comparable by HF group (P<0.05). SOD activity was significantly increased and BNP concentration was significantly decreased in liraglutide group compared to HF group (P<0.05). Conclusions These results show that liraglutide protects pressure-overload rat heart from failure possibly through reducing oxidation.

    参考文献
    [1] Nauck M, Frid A, Herrnansen K, et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes:the LEAD (1iraglutide effect and action in diabetes)-2 study[J]. Diabetes Care, 2009, 32(1): 84-90.
    [2] Liu J, Liu Y, Chen L, et al. Glucagon-like peptide-1 analog liraglutide protects against diabetic cardiomyopathy by the inhibition of the endoplasmic reticulum stress pathway. J Diabetes Res. 2013, 2013(5): 1-8.
    [3] Okerson T, Yan P, Stonehouse A, et al. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes[J].Am J Hypertens, 2010, 23(3): 334-339.
    [4] Timmers L, Henfiques JP, de Kleijn DP, et al.Exenatide infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury[J].J Am Coll Cardiol, 2009, 53(6): 501-510.
    [5] Zhao T, Parikh P, Bhashyam S,et al. Direct effects of glucagon-like peptide-l on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts[J].J Pharmacol Exp Ther, 2006, 317(3): 1106-1113.
    [6] Conrad CH,Brooks WW, Robinson KG, et al. Impaired myocardial function in spontaneously hypertensive rats with heart failure[J]. Am J Physiol, 199l, 260 (1 Pt 2): H136-145.
    [7] 王艳飞,任越,曹雪滨,等.改良慢性压力超负荷大鼠模型的对比研究[J].医学研究与教育,2010,27(6):25-27.
    [8] 王晨阳,孙卫卫,徐鹏,等.红景天苷对慢性心力衰竭大鼠肠系膜动脉舒缩作用的影响[J].解放军医药杂志,2014,26(11):11-13.
    [9] 程向娟,王雄,滕晓焕.利拉鲁肽可对抗大鼠心肌缺血再灌注损伤[J].中华心血管病杂志,2015, 43(3),259-263.
    [10] 高妍.利拉鲁肽对心血管系统的保护作用[J].中华内分泌代谢杂志,2013, 29(10): 10b1-10b4.
    [11] Noyan-Ashraf MH, Momen MA, Ban K, et al.GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice[J]. Diabetes, 2009, 58(4): 975-983.
    [12] 曾山,周欣,涂悦,等.压力容积导管系统评价卒中易感性自发性高血压大鼠左心室功能的意义[J].中华高血压杂志,2008,16(8):737-741.
    [13] 刘颖,谭波宇.乌头提取物对心衰大鼠抗氧化能力的研究[J].安徽医药,2015, 19(9):1661-1664.
    [14] 张胜叶,黄晏,赵乾,等.外源Apelin-13对大鼠阿霉素心力衰竭模型的影响与一氧化碳途径的关系[J].中华中老年心脑血管病杂志,2011, 13(5):452-455.
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王晨阳,曹海涛,张志华,华川.利拉鲁肽对大鼠压力负荷型慢性心衰的保护作用[J].中国比较医学杂志,2016,26(9):64~68.

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  • 最后修改日期:2016-03-20
  • 在线发布日期: 2016-09-22