心力衰竭大鼠不同阶段尾加压素Ⅱ和脑钠素含量变化与心功能及中医辨证的相关性研究

发布时间：2018-01-02 09:34

本文关键词：心力衰竭大鼠不同阶段尾加压素Ⅱ和脑钠素含量变化与心功能及中医辨证的相关性研究　出处：《泸州医学院》2010年硕士论文　论文类型：学位论文

【摘要】： 目的：观察大鼠在不同心功能状态尾加压素Ⅱ(urotensinⅡ, UⅡ)和脑钠素(brain natriuretic peptide, BNP)含量变化规律与中医辨证之间的相互关系,并探讨其临床意义。方法：雄性Wistar大鼠40只,体重(200±20)g,将其随机分成心力衰竭(chronic heart failure, CHF)模型组30只,生理盐水组(physiologic saline, NS)(正常对照组)10只。1.建立CHF模型：取健康雄性Wistar大鼠30只,体重(200±20)g,皮下注射异丙肾上腺素(isoprenaline, ISO) (170mg/kg,分2次,间隔24小时,用生理盐水配制成17mg／ml溶液,即10ml／kg),建立大鼠慢性心力衰竭(CHF)模型,ISO购自美国SIGMA公司。分别在用药后2、4、8周进行心功能测定,抽取静脉血测定尾加压素Ⅱ和脑钠素含量并取心肌观察病理形态学特征。2.正常对照组：取健康雄性Wistar大鼠10只,体重(200±20)g,皮下注射生理盐水0.25ml。3.模型鉴定：(1)同室常规饲养,观察大鼠的饮食、毛色、粪便、活动、紫绀、水肿等一般性状,每周称体重(body weight, BW),并根据大鼠症状及活动等表现将其分为心气虚型和阳虚水泛型。记录死亡大鼠的时间和死亡率。(2)心功能测定,经颈总动脉测量左室收缩压(left ventricular systolic pressure, LVSP),左室舒张末压(left ventricular end-diastolic pressure, LVEDP)及左室压力最大上升及下降速度(left ventricular developed pressure,±LVdp/dt)。(3)心功能测定结束后,摘取大鼠心、肝和肺,分别计算心、肝、肺脏质量指数。(4)病理切片检测：左心室心肌组织常规石蜡包埋切片,HE染色,显微镜观察。4.血浆UⅡ浓度测定：用酶联免疫法测定UⅡ含量。5.血浆脑钠素(BNP)测定,用酶联免疫法测定BNP含量。6.数据分析：所有计量资料以均数±标准差(x±s)表示,应用SPSS13.0软件包进行数据统计,方差齐性检验,单因素方差分析；多组间均数比较采用方差分析的F检验,计数资料用x2检验,相关分析采用线性相关分析,p0.05,差异无统计学意义,p0.05,差异有统计学意义,结果：1.大鼠一般情况及死亡率：与NS组大鼠比较,CHF模型组大鼠多有萎靡不振、乏力、皮毛干枯、活动和进食相对减少,体温下降、畏缩扎堆、缩肩拱背、足背水肿、唇舌紫暗或淡白等虚寒征象,死亡率为20%,而NS组无一例死亡。组间率比较p0.05,NS组大鼠一般情况无明显变化。2.大鼠心肌病理切片观察(HE染色)：NS组大鼠心肌纤维排列整齐,细胞间隙正常,无心肌纤维断裂破坏；CHF模型组大鼠心肌组织受损破坏,心肌纤维紊乱,部分断裂,心肌细胞间可见炎性细胞浸润和充血表现,部分肌源纤维溶解、消失；3.大鼠血浆UⅡ含量：与对照组比较,CHF组大鼠血浆UⅡ含量明显升高,具有显著统计学意义(p0.01),并随CHF组大鼠周期延长,即心衰程度加重,UⅡ含量也随之升高,CHF2周组(21.38±4.93) ng/ml, CHF 4周组(47.63±14.24) ng/ml, CHF 8周组(119.58±24.91) ng/ml;明显高于对照组(5.20±1.25) ng/ml的含量。各组间两两比较均有统计学意义或显著统计学意义(P0.05或P0.01)。4.大鼠血流动力学测定：与对照组比较,CHF组LVSP,±LVdp／dtmax有明显下降(P0.01)。LVEDP升高(P0.01)。5.大鼠血浆BNP含量：模型2周组BNP浓度较正常对照组升高(P0.05),模型4周组及8周组较正常对照组明显升高(P0.01)6.相关性分析：(1)血浆UⅡ水平与血浆BNP水平呈显著正相关,r=0.912(P0.01)；(2)血浆UⅡ水平与左心室收缩压(LVSP)呈显著负相关,r=-0.800(P0.01)；(3)血浆uⅡ水平与左心室收缩压最大上升速率(+dp/dt max)呈显著负相关,r=.0.894(P0.01)。结论：1.皮下注射异丙肾上腺素,可以造成病理学上明确的心肌损伤,血流动力学也证实存在充血性心力衰竭。2.模型组大鼠血浆UⅡ含量与心功能呈负相关关系,3.模型组大鼠血浆UⅡ含量与BNP含量呈正相关关系,4.血浆UⅡ含量的变化有潜力作为临床心力衰竭严重程度的客观指标,5.CHF中医证型与UⅡ水平密切相关。
[Abstract]:Objective: To observe the cardiac function in rat urotensin II (urotensin II, U II) and brain natriuretic peptide (brain natriuretic, peptide, BNP) the relationship between the changes and TCM syndrome, and to explore its clinical significance. Methods: 40 male Wistar rats, weight (200 + 20) g, were randomly divided into heart failure (chronic heart failure, CHF) 30 rats in model group, saline group (physiologic saline, NS) (normal control group) 10.1. CHF model: 30 healthy male Wistar rats, weight (200 + 20) g, subcutaneous injection of isoproterenol (isoprenaline (170mg/kg, ISO), 2 times, 24 hours apart, with normal saline into 17mg / ml solution, 10ml / kg), the establishment of rats with chronic heart failure (CHF) model, ISO was purchased from SIGMA company. In 2,4,8 weeks after treatment of cardiac function determination, venous blood determination of urotensin angiotensin II And the content of brain natriuretic peptide and myocardial pathological observation on morphological characteristics of.2. normal control group: 10 healthy male Wistar rats, weight (200 + 20) g, subcutaneous injection of saline 0.25ml.3. model identification: (1) in conventional breeding, observe the rat diet, hair color, stool, activity, cyanosis, edema and the general traits, weighed weekly (body weight, BW), and according to the rat's symptoms and activities will be divided into Qi deficiency and Yang water generic. Record the time of rat death and mortality. (2) heart function test, the measurement of left ventricular carotid artery systolic blood pressure (left ventricular systolic pressure, LVSP), left ventricular end diastolic pressure (left ventricular end-diastolic pressure, LVEDP) and left ventricular pressure maximal rising and falling speed (left ventricular developed pressure, 1 LVdp/dt). (3) measured after cardiac function, removal of rat heart, liver and lung, heart were calculated, The liver, lung mass index (4). Pathological examination: left ventricular myocardium tissue paraffin sections, HE staining, microscopic observation of.4. plasma U II U II.5. content determination: Determination of plasma brain natriuretic peptide by enzyme linked immunosorbent assay (BNP) determination, determination of.6. data analysis with BNP by ELISA immunoassay: all measurement data to mean + standard deviation (x + s) said that the application of SPSS13.0 software package for statistical data, ANOVA test, one-way ANOVA; multiple groups were compared by analysis of variance F test, count data using x2 test, correlation analysis using linear correlation analysis. P0.05, there was no statistically significant difference, P0.05, the difference was statistically significant, results: the general situation and the mortality rate was 1. in rats: compared with NS rats, CHF rats of model group have low-spirited, fatigue, skin dryness, eating and activity of relative reduction, the temperature decreased to Za, shrinkage Shoulder arch, dorsal foot edema, tongue dark purple or pale white deficiency signs, the mortality rate was 20%, while in NS group, no patient died. The rate of groups was P0.05 NS, the general condition of the rats had no obvious change to observe the myocardial pathological.2. rats (HE staining) of myocardial fibers of rats in the:NS group arranged neatly cells, normal space, no destruction of muscle fiber fracture; CHF group: myocardial tissue damage, myocardial fibers disorder, fracture, myocardial cells can be seen between the expression of inflammatory cell infiltration and hyperemia, part of the muscle fiber source dissolved and disappeared; plasma U II content of 3. rats: compared with the control group, plasma U II the content of CHF group rats increased significantly, with statistical significance (P0.01), and with the CHF rats, prolong the period of heart failure exacerbation, namely, U II content also increased, CHF2 weeks group (21.38 + 4.93) ng/ml, CHF 4 weeks group (47.63 + 14.24) ng/ml, CHF 8 weeks group (119.58 + 24.91) ng/ Ml; was significantly higher than the control group (5.20 + 1.25) ng/ml content. 22 groups were statistically significant or significant (P0.05 or P0.01) determination of.4. hemodynamics of rats: compared with the control group, CHF group, LVSP + LVdp / dtmax decreased significantly (P0.01).LVEDP (P0.01) BNP content increased rat plasma.5.: 2 weeks model group, the concentration of BNP increased compared to normal control group (P0.05), model 4 week group and 8 week group was obviously higher than normal control group (P0.01) 6. correlation analysis: (1) the plasma U II level was positively correlated with the plasma levels of BNP, r=0.912 (P0.01 (2); the plasma levels of U II) and the left ventricular systolic pressure (LVSP) was significantly negatively related to r=-0.800 (P0.01); (3) on plasma u level and left ventricular systolic maximum pressure rise rate (+dp/dt max) was significantly negatively related to r=.0.894 (P0.01). Conclusion: 1. subcutaneous injection of isoproterenol, can cause pathology of clear Myocardial injury, hemodynamics also confirmed the presence of congestive heart failure.2. model rats on plasma U levels and heart function was negatively correlated, 3. rats of model group plasma U II content correlated positively with the content of BNP, 4. changes on plasma U content has the potential as an objective index of clinical severity of heart failure. Closely related to TCM Syndromes of 5.CHF and U II level.

【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R-332

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