痰瘀互结证慢性心肌缺血小型猪模型的建立
담어호결증만성심기결혈소형저모형적건립
Establishment of a minipig model of chronic myocardial ischemia of phlegm-blood stasis syndrome type
  • 万方数据
    中国比较医学杂志 중국비교의학잡지
    Chinese Journal of Comparative Medicine
    2015年 9期 1-7 ,共7页

    潘永明%陈亮%徐孝平%朱科燕%徐剑钦%陈民利

    반영명%진량%서효평%주과연%서검흠%진민리

    痰瘀互结证%慢性心肌缺血模型%小型猪 痰瘀互結證%慢性心肌缺血模型%小型豬
    담어호결증%만성심기결혈모형%소형저
    Phlegm-blood stasis syndrome%Chronic myocardial ischemia model%Minipig
    目的：采用高脂、静脉注射维生素D3（ VD3）和异丙肾上腺素建立痰瘀互结证慢性心肌缺血小型猪模型。方法15只雄性巴马小型猪随机分成正常对照（Ctr）组、高脂（HFC）组和痰瘀互结证心肌缺血模型（CMI）组，每组5只，Ctr组饲喂普通饲料，HFC组饲喂高脂饲料，CMI组采用高脂饮食、静脉注射VD3和异丙肾上腺素联合建立痰瘀证慢性心肌缺血模型，连续造模24周，分别通过测定动物体重、心电图、活动、血脂、心肌酶、血液流变学、炎症、心脏指数（ CI）和心肌缺血面积（ MIS）来评价模型的建立及痰瘀互结证的病理进程。结果与Ctr组， HFC组体重、心率（ HR）、总胆固醇（ TC）、低密度脂蛋白（ LDL－C）、高密度脂蛋白（ HDL－C）、动脉粥样硬化指数（AI）、低、中、高切全血粘度和还原粘度、红细胞电泳时间（EPT）、超敏C－反应蛋白（hs－CRP）和白介素－6（IL－6）水平均明显升高（P＜0．05， P＜0．01）；CMI组体重、HR、24 h总的ST段升高数（∑ST）、24 h内平均ST段升高数（ST＿average）、活动度、TC、甘油三酯（TG）、LDL－C、HDL－C、AI、肌酸激酶（CK）、乳酸脱氢酶（LDH）、肌钙蛋白－1（cTn－1）、低、中、高切全血粘度和还原粘度、EPT、卡松粘度（CV）、hs－CRP、IL－6、CI和MIS均显著升高（P＜0．05， P＜0．01），脂联素（APN）水平则显著降低（P＜0．05）；与HFC组比，CMI组AI、CK、LDH、cTn－1、低、中、高切全血粘度、EPT、CI和MIS均明显高于HFC组（P＜0．05， P＜0．01），且APN水平则显著低于HFC组（P＜0．05）。相关分析显示，MIS与TC、LDL－C、AI、CK、LDH、cTn－1、APN、高、中、低切全血粘度、EPT、CV、hs－CRP和IL－6有关（ P＜0．05， P＜0．01），同时线性回归分析显示，痰瘀与TC、LDL－C、AI、CK、LDH、cTn－1、APN、EPT、CV、hs－CRP和IL－6有关（P＜0．01），进一步线性逐步回归分析显示痰瘀衍变与TC、CK和IL－6密切相关（P＜0．01）。结论高脂喂养和注射VD3和异丙肾上腺素能成功建立痰瘀互结证慢性心肌缺血小型猪模型，且脂质代谢、血液流变学、心肌酶代谢和炎症可作为痰瘀互结证的客观生化物质基础，这些变化可反映了中医理论“痰瘀互结、瘀毒致变”的相关生物学基础。
    목적：채용고지、정맥주사유생소D3（ VD3）화이병신상선소건립담어호결증만성심기결혈소형저모형。방법15지웅성파마소형저수궤분성정상대조（Ctr）조、고지（HFC）조화담어호결증심기결혈모형（CMI）조，매조5지，Ctr조사위보통사료，HFC조사위고지사료，CMI조채용고지음식、정맥주사VD3화이병신상선소연합건립담어증만성심기결혈모형，련속조모24주，분별통과측정동물체중、심전도、활동、혈지、심기매、혈액류변학、염증、심장지수（ CI）화심기결혈면적（ MIS）래평개모형적건립급담어호결증적병리진정。결과여Ctr조， HFC조체중、심솔（ HR）、총담고순（ TC）、저밀도지단백（ LDL－C）、고밀도지단백（ HDL－C）、동맥죽양경화지수（AI）、저、중、고절전혈점도화환원점도、홍세포전영시간（EPT）、초민C－반응단백（hs－CRP）화백개소－6（IL－6）수평균명현승고（P＜0．05， P＜0．01）；CMI조체중、HR、24 h총적ST단승고수（∑ST）、24 h내평균ST단승고수（ST＿average）、활동도、TC、감유삼지（TG）、LDL－C、HDL－C、AI、기산격매（CK）、유산탈경매（LDH）、기개단백－1（cTn－1）、저、중、고절전혈점도화환원점도、EPT、잡송점도（CV）、hs－CRP、IL－6、CI화MIS균현저승고（P＜0．05， P＜0．01），지련소（APN）수평칙현저강저（P＜0．05）；여HFC조비，CMI조AI、CK、LDH、cTn－1、저、중、고절전혈점도、EPT、CI화MIS균명현고우HFC조（P＜0．05， P＜0．01），차APN수평칙현저저우HFC조（P＜0．05）。상관분석현시，MIS여TC、LDL－C、AI、CK、LDH、cTn－1、APN、고、중、저절전혈점도、EPT、CV、hs－CRP화IL－6유관（ P＜0．05， P＜0．01），동시선성회귀분석현시，담어여TC、LDL－C、AI、CK、LDH、cTn－1、APN、EPT、CV、hs－CRP화IL－6유관（P＜0．01），진일보선성축보회귀분석현시담어연변여TC、CK화IL－6밀절상관（P＜0．01）。결론고지위양화주사VD3화이병신상선소능성공건립담어호결증만성심기결혈소형저모형，차지질대사、혈액류변학、심기매대사화염증가작위담어호결증적객관생화물질기출，저사변화가반영료중의이론“담어호결、어독치변”적상관생물학기출。
    ObjectiveToestablishadiseasesyndromecombinedanimalmodel,theminiaturepigmodelof&nbsp;chronic myocardial ischemia of phlegm-blood stasis syndrome type , by high fat/cholesterol diet feeding and intravenous injection with VD3 and isoproterenol.Methods Miniature pigs were randomly divided into the control (Ctr) group, high fat/cholesterol diet ( HFC) group and chronic myocardial ischemia model of phlegm-blood stasis syndrome ( CMI) group, 5 pigs in each group .The Ctr group was fed with normal regular chow diet , HFC group was fed with high fat/cholesterol diet , while the CMI group was fed with high fat/cholesterol diet and intravenous injection with VD 3 and isoproterenol .The experiment lasted for 24 weeks.The model establishment and its pathological process of phlegm-blood stasis syndrome were evaluated by examinations of body weight , electrocardiogram, activity, blood lipid, myocardial enzymes, hemorheology, inflammation, cardiac index(CI) and myocardial ischemia size (MIS).Results Compared with the Ctr group, the body weight, heart rate(HR), Total cholesterol(TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol ( HDL-C ) , atherosclerosis index ( AI ) , low/middle/high shear rate of whole blood viscosity and reduced viscosity, erythrocyte electrophoresis time(EPT), high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels in the HFC group were significantly increased (P <0.05, P <0.01), while the body weight, heart rate, total ST, ST_average, activity, TC, TG, LDL-C, HDL-C, AI, CK, LDH, cTn-1, low/middle/high shear rate of whole blood viscosity and reduced viscosity, EPT, Casson viscosity(CV), hs-CRP, IL-6, CI and MIS in the CMI group were significantly increased (P<0.05, P<0.01), and APN level in the CMI group was significantly decreased (P<0.05).Moreover, AI, CK, LDH, cTn-1, low/middle/high shear rate of whole blood viscosity , EPT, CI and MIS in the CMI group were significantly higher than those of HFC group (P<0.05, P<0.01), while APN in the CMI group was significantly lower than that of HFC group (P<0.05).Correlation analysis showed that MIS was closely correlated to TC , LDL-C, AI, CK, LDH, cTn-1, APN, high/middle/low shear rate of whole blood viscosity , EPT, CV, hs-CRP and IL-6 (P<0.05, P<0.01).The linear regression analysis also showed that phlegm-blood stasis was closely correlated to TC , LDL-C, AI, CK, LDH, cTn-1, APN, CV, EPT, hs-CRP, and IL-6 ( P <0.01), and further linear stepwise regression analysis showed that the evolution of phlegm-blood stasis was closely related to TC , CK and IL-6.Conclusions Minipig model of chronic myocardial ischemia of phlegm-blood stasis syndrome type can be established by high fat /cholesterol diet feeding and intravenous injection with VD 3 and isoproterenol .Their blood lipid metabolism , hemorheology , myocardial enzymes and inflammatory indexes can be used as external biochemical basis of phlegm-blood stasis syndrome type , which may reflect related biological basis of the traditional Chinese medicine theory of “phlegm and stasis cementation , blood-stasis & toxin causing catastrophe”.
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