有氧运动改善自发性高血压大鼠心肌胰岛素抵抗的作用及机制初探

【作者】 王伟；

【导师】 张昆茹；

【作者基本信息】 陕西师范大学 ， 运动人体科学， 2012， 硕士

【摘要】 实验目的：许多疾病的发生发展都和胰岛素抵抗有关,如Ⅱ型糖尿病、冠心病和高血压病等重大疾病。胰岛素抵抗是一种病理状态,当细胞的胰岛素受体或受体后信号转导发生障碍时会引起胰岛素抵抗。高血压是目前发病率较高的一种疾病,以往的研究主要集中在高血压与血管胰岛素抵抗这一方面,对高血压心肌胰岛素抵抗的研究较少。新近的研究表明：高血压大鼠存在心肌胰岛素抵抗,这和心肌PPARγ的表达减少及其下游的PI3K-Akt信号通路的障碍有关。大量的临床及实验证实,运动是改善胰岛素敏感性最经济,最有效,最安全的方法。但关于运动对高血压大鼠心肌胰岛素敏感性的的研究较少,其机制也并不完全清楚。因此本实验主要观察运动对高血压大鼠心肌胰岛敏感性的影响,并对其机制进行初步的探讨,尤其是PPAR Y及其下游的PI3K-Akt信号通路在其中的作用。实验方法：通过建立高血压大鼠长期有氧运动模型,使用BP-6A全自动无创血压测量系统测血压,在整体实验水平观察运动对高血压大鼠心肌血流动力学的影响及运动对心肌胰岛素敏感性的的作用,并用Western blot等方法检测心肌PPAR γ及Akt蛋白表达的变化。实验结果：(1)和WKY大鼠相比,SHR大鼠体重明显下降,但两者的心脏重量没明显区别,SHR大鼠的心脏/体重比值即心系数明显上升,说明高血压大鼠存在一定程度的心肌肥厚(P<0.01,n=10)。运动可使高血压大鼠的体重下降,心脏重量增加,心系数进一步增大,这可能和运动引起的适应性的心肌肥厚有关,是心脏的一种良性适应(P<0.01,n=10)。(2)和WKY大鼠相比,同龄的SHR大鼠收缩压和舒张压均明显升高；与SHR对照组相比,SHR运动组的收缩压和舒张压均明显降低(P<0.05,n=10),说明运动可以有效防治高血压。(3)和WKY大鼠相比,SHR对照组大鼠空腹血糖浓度显著升高(P<0.01,n=10)；和SHR对照组相比,SHR运动组血糖浓度显著下降(P<0.01,n=10),说明运动可以降低高血压的空腹血糖浓度。(4)给予胰岛素后,WKY大鼠心脏的±LV dP/dtmax增快(与SHR对照组相比,P<0.05,n=8),SHR运动组大鼠心脏的±LV dP/dtmax增快, SHR组±LVdP/dtmax变化不大(P<0.05,n=8)；和SHR相比,运动可使胰岛素诱导SHR心脏的±LV dP/dtmax升高(P<0.05,n=10)。说明运动可以提高心肌在整体水平对胰岛素的反应,降低高血压大鼠心肌胰岛素抵抗。(5)与WKY大鼠相比,SHR对照组大鼠Akt、PPAR γ蛋白的表达显著减少(P<0.01,n=4)；与SHR对照组相比SHR运动组大鼠Akt、PPAR γ蛋白的表达显著增多(P<0.01,n=4),说明运动可以提高高血压大鼠心肌Akt、PPARγ的表达。结论：(1)有氧运动可以有效降低自发性高血压大鼠的收缩压和舒张压,对高血压有一定的防治作用；(2)高血压大鼠存在明显的整体和心肌胰岛素抵抗,而心肌胰岛素的抵抗和心肌Akt、PPAR γ蛋白的表达减少有关；(3)有氧运动可以明显改善心肌胰岛素抵抗,提高心肌的胰岛素敏感性,这可能和运动增加心肌Akt、PPAR γ表达有关。更多还原

【Abstract】 Objective:Insulin resistance can lead to the start and development of big diseases, such as Ⅱ type diabetes, coronary heart disease and high blood pressure etc. Insulin resistance, a kind of pathological condition, can be caused after cells’ insulin receptor or when signaling transduction is disturbed after the receptor. High blood pressure is one of high incidence of diseases. So previously, researches mainly focus on studying high pressure and blood vessel insulin, while only a few researches focus on studying myocardium insulin resistance. Recent researches show that there exists insulin resistance in rats with high blood pressure. A large amount of clinical examinations and experiments prove that doing exercises is the most economical, effective and secure way in improving insulin susceptibility. But there is only a small amount of researches on studying how much benefits the exercises will do to myocardium insulin of rats with high blood pressure. Besides, its mechanism is not clear. So this experiment pays much attention to what impacts exercises will make on myocardium insulin susceptibility of rats with high blood pressure and also explores the first-step discussion on its mechanism. Especially, the effects of the pI3K-Akt signaling pathway, the downstream of PPARy, will be discussed.Methods:Build a long-terme on myocardium Hemodynamic of rats with high blood pressure and what the effects of myocardium insulin susceptibility are. And test myocardium PPARy and Akt protein expressio aerobics model for rats with high blood pressure. Observe what impacts exercises will makn by using Western blot.Results:(1) Compared with rats in WKY group, the weights of rats in SHR group decrease greatly. But heart weights of rats in these two groups are almost the same. The ratio between heart weight and weight of rats in SHR group increases distinctly, which proves that rats with high blood pressure have myocardium hypertrophy. Exercises can decrease the weight, increase heart weight and increase heart coefficient of rats with high blood pressure. It may be concerned with adaptive myocardium hypertrophy caused by exercises, which is a kind of benign adaptation of heart (P<0.01,n=10)(2) Compared with rats in WKY group, the systolic blood pressure and diastolic blood pressure of rats at the same age in SHR group increase greatly. Compared with rats in SHR group, the systolic blood pressure and diastolic blood pressure of rats in exercises group decrease greatly (P<0.05, n=10). The above information proves that exercises can prevent high blood pressure.(3) Compared with rats in WKY group, blood sugar levels of SHR rats on empty stomach increase greatly (P<0.01,n=10). Compared with rats in SHR group, blood sugar levels of rats in exercises group decrease greatly (P<0.01,n=10). The above information proves that exercises can reduce blood sugar level on empty stomach of rats with high blood pressure.(4) The heart±LV dP/dtmax of rats in WKY group and in SHR exercises group beats quickly after injecting insulin (compared with SHR group after injecting insulin (compared with SHR group, P<0.05, n=8). The heart±LV dP/dtmax of rats in SHR group beats almost normally (P<0.05, n=8). Exercises can increase heart±LV dP/dtmax of rats in SHR group by insulin induction (P<0.05,n=10). The above information proves that exercises can increase myocardium and reduce myocardium insulin resistance.(5) Compared with rats in WKY group, Akt and PPARy protein expression of rats in SHR group decreases greatly (P<0.01,n=10). Compared with rats in SHR group, Akt and PPARy protein expression of rats in SHR exercises group increases greatly (P<0.01,n=10)Conclusions:We can come to the conclusions as follows:(1) Aerobics can reduce the systolic blood pressure and diastolic blood pressure of rats with high blood pressure, which can prevent high blood pressure in some degree..(2) There exists obvious myocardium insulin resistance in rats with high blood pressure, and myocardium insulin resistance is concerned with the decrease of myocardium Akt and PPARy protein expression.(3) Aerobics can improve myocardium insulin resistance significantly and increase myocardium insulin susceptibility, which may be concerned with the increase of myocardium Akt and PPARy protein expression after exercises.更多还原