Establishment of a minipig model of chronic myocardial ischemia of phlegm-blood stasis syndrome type
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    Abstract:

    Objective To establish a disease syndrome combined animal model, the miniature pig model of 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 VD3 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 VD3 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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History
  • Received:
  • Revised:July 24,2015
  • Adopted:
  • Online: September 30,2015
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