左旋精氨酸通过激活L-arg-NO通路对异丙肾上腺素致大鼠心力衰竭的作用  

The effects of L-arginine on heart failure rats induced by isoprenaline through activating L-arg-NO pathway

作　　者：李伟建[1] 方达[1] 梁利军[1] 吴玉蕾[1] 潘睿晗 于越[1] 刘晓凡[2] 桑黎黎[2] 

机构地区：[1]徐州医学院临床医学系,徐州221002 [2]徐州医学院机能实验中心,徐州221002

出　　处：《安徽医科大学学报》2015年第12期1716-1720,共5页Acta Universitatis Medicinalis Anhui

基　　金：江苏省高等学校大学生创新创业训练计划(编号:201410313056X);徐州医学院院级科研课题(编号:2014KJ11);国家级大学生创新创业训练计划项目(编号:20130313021)

摘　　要：目的探究左旋精氨酸(L-arg)通过激活L-arg-NO通路对异丙肾上腺素(ISO)导致的大鼠心力衰竭的保护作用。方法雄性SD大鼠随机分为对照组、ISO组、L-arg干预组。腹腔注射ISO复制大鼠心力衰竭模型,灌胃给予L-arg。30 d后监测血流动力学参数:心率(HR)、左室收缩压力(LVSP)、左室舒张末期压力(LVEDP)、左室压力最大上升或下降速率(±dp/dtmax),计算心肺系数,检测血清超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)含量以及一氧化氮合酶(NOS)活性;HE染色观察心肌组细胞排列;Masson染色观察心肌胶原纤维并计算心肌胶原纤维容积分数(CVF)。结果与对照组比较,ISO组大鼠血流动力学参数:HR、LVSP、+dp/dtmax降低,LVEDP、-dp/dtmax升高,心肺系数增加,血清TNF-α、SOD升高,NO、NOS降低,差异均有统计学意义(P<0.05)。L-arg干预组HR、LVSP、+dp/dtmax均高于ISO组,LVEDP、-dp/dtmax、心肺系数低于ISO组,血清SOD和TNF-α降低,NO和NOS增加,差异均有统计学意义(P<0.05)。HE染色显示对照组心肌细胞形态正常,间质无扩张充血,心肌细胞排列整齐;ISO组心肌细胞排列紊乱,炎性细胞浸润,而L-arg干预组心肌细胞接近对照组。ISO组Masson染色心肌细胞间可见大量蓝染的胶原纤维,而对照组观察不到蓝染区域,L-arg干预组在对照组与ISO组之间;ISO组CVF明显高于L-arg干预组(P<0.05),L-arg干预组高于对照组(P<0.05)。结论 L-arg可以通过激活Larg-NO通路,增加机体内NO含量,改善血流,减轻心肌重构,产生对心力衰竭心肌的保护作用。Objective To explore the effects of L-arginine（L-arg） by activating L-arg-NO pathway on heart failure rats induced by isoprenaline （ISO）. Methods Male SD rats were randomly divided into three groups： control group, ISO group, L-arg group. Heart failure model was made by injecting ISO and L-arg was given by gavage. After thirty days, each group was monitored with hemodynamic parameters by carotid artery intubation： heart rate （HR）, left ventricular systolic pressure （LVSP） , left ventricular end-diastolic pressure （LVEDP）, maximal or minimal differentials of left ventricular developed pressure （ ±dp/dtmax ）. Heart and lung indices were calculated. Superoxide dismutase （SOD）, tumor necrosis factor-α （TNF-α） and nitric oxide （NO） concentration and nitric oxide syntheses （NOS） activity in plasma of each group were determined. Myocardial tissue changes were analyzed by HE staining. Myocardial fibers changes and collagen volume fraction （CVF） were analyzed by Masson trichrome staining. Results HR, LVSP and ＋ dp/dtmax in L-arg group were higher than those in ISO group;LVEDP and - dp/dt in L-arg group were lower than that in ISO group（P 〈 0. 05）. L-arg decreased the heart and lung indices （ P 〈 0.05 ）. Meanwhile, the TNF-α and SOD level of L-arg group were decreased than those of ISO group （ P 〈 0.05）. At the same time, the NO concentration and NOS activity of L-arg increased than those of ISO group （P 〈 0. 05 ）. The myocardial arranged disorder, lots of inflammatory cells and interstitial collagen due to isoprenalinc in- jection, L-arg supplements improved the heart function induced by ISO. There were a large number of blue-stained collagen fibers among derangement of myocardial cells in ISO group. But there was rarely the blue-stained region in the control group and L-arg group. CVF in ISO group was higher than L-arg group（P 〈0.05） , CVF in L-arg group was higher than the control group （P 〈 0. 05 ）. Conclusion Exogenous L-arg can

关 键 词：左旋精氨酸 L-arg-NO通路 异丙肾上腺素 心力衰竭 

分 类 号：R364.31[医药卫生—病理学]