慢性肾功能衰竭微炎症状态下心力衰竭的大鼠模型研制及其心衰机制研究

发布时间：2018-03-01 09:43

本文关键词： 慢性肾功能衰竭肾透析微炎症慢性心力衰竭超声心动描记术　出处：《石河子大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:研制慢性肾功能衰竭(CKD)微炎症状态下心力衰竭大鼠模型并探索其心衰机制。方法:SD大鼠70只,随机分为3组:对照组(10只)食用油10ml·kg-1·d-1灌胃,1次/d;CKD组(30只)3%腺嘌呤食用油10ml·kg-1·d-1灌胃;造模组(30只)初始腺嘌呤灌胃同CKD组,Scr升高1.5倍腺嘌呤灌胃减为1次/3d,开始腹腔注射阿霉素2.5mg/kg,1次/7d,10 mg/L溴酸钾溶液代替饮水。监测肾功、C-反应蛋白及心脏超声。造模成功后对比各组心脏超声、全心质量指数(HM/BM)及左心室质量指数(LVM/BM)、病理学特点。对比各组基质金属蛋白酶-2、9(MMP-2、9)及基质金属蛋白酶抑制剂-1(TIMP-1),VG染色病理学及胶原面积百分比,电镜超微结构及心肌细胞的凋亡。结果:(1)模型达标情况:从CKD、心力衰竭和微炎性反应评价,造模达标。(2)心脏超声:造模组左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)升高,收缩末期室间隔厚度(IVSs)、左心室收缩末期后壁厚度(LVPWs)降低,缩短分数(FS)、左室射血分数(LVEF)下降,与对照组及CKD组有统计学差异(P均0.05);CKD组与对照组相比LVESd、LVESV升高,FS、LVEF下降(P均0.05)。(3)HM/BM及LVM/BM:与对照组相比,CKD组及造模组增高(P均0.05),但两组间无统计学差异。(4)病理学:HE染色造模组心肌细胞及纤维破坏伴单核细胞浸润;CKD组病变较轻且不伴炎细胞浸润。VG染色及电镜超微结构中,CKD组及造模组心肌病理损伤逐渐加重,VG染色各组胶原面积与所测视野的面积比分别为0.132、0.151、0.053。(5)金属蛋白酶测定:MMP-2,造模组低于对照组及CKD组;CKD组低于对照组,差异接近但尚未达统计学标准(P=0.058)。MMP-9和TIMP-1,各组间无统计学差异,但其比值随着心衰程度的逐渐加重而显著升高,除CKD组与造模组差异接近但尚未达统计学标准外(P=0.055),其他均有统计学意义。(6)细胞凋亡测定:未见心肌细胞凋亡。结论:(1)腺嘌呤灌胃联合阿霉素腹腔注射,溴酸钾溶液饮水可建立慢性肾功能衰竭微炎症状态下心力衰竭大鼠模型。(2)慢性肾功能衰竭微炎症状态下大鼠心力衰竭的机制是心功能下降、心脏相对增重及相应的心肌病理损害,并出现心肌细胞外基质减少,心室重构明显,但尚未出现心肌细胞凋亡。(3)除心脏相对增重外,单纯CKD上述其他表现均明显轻于慢性肾功能衰竭微炎症状态下心力衰竭。
[Abstract]:Objective: to develop a rat model of heart failure induced by chronic renal failure (CKD) microinflammation and to explore the mechanism of heart failure. The rats were randomly divided into three groups: control group (n = 10): 10 ml 路kg-1 路d ~ (-1) of edible oil (n = 30) were perfused with 10 ml 路kg-1 路d ~ (-1) of 3% adenine. 30 rats in the model group) the initial adenine administration was 1. 5 times higher than that in the CKD group. Adenine administration was reduced to 1 / 3 d, and was injected intraperitoneally with doxorubicin 2.5 mg / kg / 1 / 7 d / 10 mg/L potassium bromate solution instead of drinking water. Renal function C-reactive protein (CRP) and cardiac ultrasound were monitored. After the model was successful, the echocardiography of each group was compared. Total cardiac mass index (HM / BMN) and left ventricular mass index (LVM / BMN), histopathological characteristics, pathological characteristics, and matrix metalloproteinase inhibitor (MMP-2) and matrix metalloproteinase inhibitor (TIMP-1 / VG) staining were compared in each group. Ultrastructure of electron microscope and apoptosis of cardiomyocytes. Results: CKD, heart failure and microinflammatory response were evaluated from CKD, heart failure and microinflammatory response. Cardiac ultrasound: left ventricular end-diastolic diameter (LVED), left ventricular end-systolic diameter (LVES), left ventricular end-diastolic volume (LVEDVV), left ventricular end-systolic volume (LVESVV) were increased in model group. The left ventricular posterior wall thickness (LVPWs) decreased, the left ventricular ejection fraction (LVEF) decreased, the left ventricular ejection fraction (LVEF) decreased, the left ventricular septal thickness decreased, the left ventricular posterior wall thickness (LVPWs) decreased, and the left ventricular ejection fraction (LVEF) decreased. There was significant difference between CKD group and control group (P < 0.05). Compared with control group, LVESdsLVESV increased and LVEF decreased (P < 0.05). HM-BM and LVM-BM: compared with control group, CKD group and model group were 0.05p, but there was no statistical difference between two groups. Myocardial cell and fiber destruction with monocyte infiltration in CKD group with mild lesion and no inflammatory cell infiltration. VG staining and ultrastructural changes of cardiomyopathy in CKD group and model group were gradually aggravated. The area ratio of visual field to visual field was 0.132 / 0.151 / 0.053.5) the ratio of metalloproteinases to MMP-2 in the model group was lower than that in the control group and the CKD group was lower than that in the control group, and that in the CKD group was lower than that in the control group. The difference was close but not up to the statistical standard. There was no statistical difference among the three groups, but the ratio increased with the increase of heart failure. Except that the difference between CKD group and model group was similar but not up to the statistical standard, there was no myocardial apoptosis. Conclusion: 1) adenine plus adriamycin was injected intraperitoneally. Potassium bromate solution can establish a rat model of chronic renal failure induced by microinflammation) the mechanism of heart failure in rats with microinflammation of chronic renal failure is the decrease of cardiac function. The relative weight gain of the heart and the corresponding pathological damage of cardiomyopathy resulted in the decrease of extracellular matrix and ventricular remodeling, but no cardiomyocyte apoptosis was found, except for the relative weight gain of the heart. All the other findings mentioned above in CKD alone were significantly less than those in chronic renal failure with microinflammation.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692.5;R541.6;R-332

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