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麦粒灸对阿霉素毒性心肌病的效应观察及其抗氧化应激机制研究

发布时间:2018-10-21 13:00
【摘要】:目的:观察麦粒灸对阿霉素(Adriamycin,ADR)所致毒性心肌病模型大鼠的效应及其抗氧化应激作用的可能机制。方法:将60只无特定病原体(Specific pathogen Free,SPF)级泼累格·多雷(Sprague-Dawley,SD)大鼠随机分为空白组、ADR毒性心肌病模型对照组(即模型组)及ADR+麦粒灸组(即麦粒灸组),每组20只[1]。各组相同环境饲养,模型组及麦粒灸组予尾静脉注射ADR造模;空白组尾静脉注射等量的生理盐水,不施灸,只接受与其它两组相同方式的抓取固定;麦粒灸组在给药的同时取"内关"、"巨阙"穴进行麦粒灸治疗[1]。共持续4周[1]。末次治疗结束 24h 后测定大鼠心率(heart rate,HR)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室舒张压(left ventricular diastolic pressure,LVDP)、等容收缩期左心室内压最大上升速率(+dp/dtmax)、等容舒张期左心室内压最大下降速率(-dp/dtmax)、左室内压变化时间(t-dp/dtmax)评价心功能[1];麻醉,取各组大鼠血样及心脏,光学显微镜下察看心肌病理形态结构改变[1];制备血清及心肌组织匀浆,酶联免疫法(enzyme-linked immuno sorbent assay,ElISA)检测血清中的乳酸脱氢酶(lactate dehydrogenase,LDH)、磷酸肌酸激酶(creatine kinase,CK)活性及心肌cTnI浓度;心肌组织中超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)的活性[1]。结果:(1)模型组的HR、LVSP、+dp/dtmax、-dp/dtmax均较空白组及麦粒灸组低,LVDP和t-dp/dtmax则升高,差异有统计学意义(P0.05);与模型组比较,麦粒灸组HR、LVSP、+dp/dtmax、-dp/dtmax升高,LVDP 和 t-dp/dtmax降低,差异有统计学意义(P0.05)。(2)与空白组比较,模型组的心肌组织光镜下呈ADR心肌病样改变:细胞肿胀充血、肌纤维部分溶解且排列紊乱,白细胞浸润明显;与模型组比较,麦粒灸组光镜下心肌细胞轻微肿胀、出血,白细胞浸润不明显[1]。(3)模型组、麦粒灸组大鼠血清LDH、CK酶活性,心肌cTnI浓度及MDA活性均较空白组显著升氋(P0.01),心肌SOD活性则显著下降(P0.05);与模型组比较,麦粒灸组大鼠血清LDH、CK酶活性、心肌cTnI浓度及MDA活性显著降低(P0.01),心肌SOD活性显著升高(P0.05)。结论:麦粒灸可提高心肌收缩能力,改善心功能,减轻ADR引起的心肌细胞肿胀、充血及炎症反应,显著降低血清LDH、CK活力,cTnI浓度及心肌组织MDA活性,同时显著升高心肌组织中SOD的活性,实现对ADR毒性心肌病大鼠的抗氧化应激作用。其机制可能与麦粒灸提高SOD活性,同时降低MDA活性来减轻过氧化产物对心肌的损伤,进而最终调控相关的抗氧化信号通路来发挥心肌保护效应有关。
[Abstract]:Aim: to observe the effect of grain moxibustion on adriamycin (Adriamycin,ADR) induced cardiomyopathy model rats and the possible mechanism of antioxidant stress. Methods: sixty Sprague-Dawley,SD rats with no specific pathogen (Specific pathogen Free,SPF) were randomly divided into blank group, model group (model group) and ADR moxibustion group (20 rats in each group). Each group was fed in the same environment, the model group and the wheat grain moxibustion group were injected with ADR by caudal vein, and the blank group was injected with the same amount of normal saline, without moxibustion, only accepted grasping and fixing in the same way as the other two groups. Grain moxibustion group was treated with grain moxibustion at the same time as "Neiguan" and "Juque". It lasted for 4 weeks [1]. Heart rate (heart rate,HR), left ventricular systolic pressure (left ventricular systolic pressure,LVSP), left ventricular diastolic pressure (left ventricular diastolic pressure,LVDP), maximum rate of left ventricular pressure rise (dp/dtmax) during isovolumic systolic period (Isovolumic diastolic phase), maximum rate of decrease of left ventricular pressure during isovolumic diastolic period (IVDD) were measured 24 hours after the end of the last treatment. Rate (- dp/dtmax), left ventricular pressure change time (t-dp/dtmax) to evaluate cardiac function [1]. Blood samples and heart samples were taken from each group of rats, and the morphologic changes of cardiomyopathy were observed under optical microscope [1]. Serum and myocardial tissue homogenate were prepared. The activities of lactate dehydrogenase (lactate dehydrogenase,LDH), creatine phosphokinase (creatine kinase,CK), myocardial cTnI and the activities of superoxide dismutase (superoxide dismutase,SOD) and malondialdehyde (malondialdehyde,MDA) were detected by enzyme linked immunosorbent assay (enzyme-linked immuno sorbent assay,ElISA). Results: (1) the HR,LVSP, dp/dtmax,-dp/dtmax of the model group was lower than that of the blank group and the wheat grain moxibustion group, while the LVDP and t-dp/dtmax levels were higher than those of the control group (P0.05), and compared with the model group, the HR,LVSP, dp/dtmax,-dp/dtmax, LVDP and t-dp/dtmax in the model group were significantly higher than those in the control group (P0.05). (2). The myocardial tissue of the model group showed ADR cardiomyopathy changes under light microscope: the cells were swollen and congested, the muscle fibers were disintegrated and arranged disorderly, the infiltration of white blood cells was obvious, compared with the model group, the myocardial cells in the moxibustion group were slightly swollen and bleeding under light microscope. (1) WBC infiltration was not obvious [1]. (3) Serum LDH,CK enzyme activity, myocardial cTnI concentration and MDA activity were significantly increased in model group and wheat grain moxibustion group compared with blank group (P0.01), and myocardial SOD activity decreased significantly (P0.05), compared with model group, LDH,CK enzyme activity in serum of wheat grain moxibustion group was significantly higher than that of control group (P0.01). Myocardial cTnI concentration and MDA activity decreased significantly (P0.01), myocardial SOD activity increased significantly (P0.05). Conclusion: grain moxibustion can improve myocardial contractility, improve cardiac function, reduce myocardial cell swelling, congestive and inflammatory reaction induced by ADR, decrease serum LDH,CK activity, cTnI concentration and MDA activity in myocardial tissue. At the same time, the activity of SOD in myocardial tissue was significantly increased, and the antioxidant stress was achieved in ADR induced cardiomyopathy rats. The mechanism may be related to the increase of SOD activity by grain moxibustion and the decrease of MDA activity in order to reduce the myocardial injury caused by peroxidation products and ultimately regulate the related antioxidant signaling pathway to exert myocardial protection effect.
【学位授予单位】:南京中医药大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R245

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