| Aim:To explore the expression of MMP-8 and its correlation with cardiac function indexes of STEMI(acute ST segment elevation myocardial infarction) patients and its effect and mechanism.Methods:100 cases of STEMI patients who went through PCI and 50 cases of healthy volunteers were selected. Echocardiography were used to check ejection fraction(EF),left ventricular end systolic diameter(LVESD), left ventricular end diastolic diameter thickness, heart function index(LVEDD). The expressions of MMP-2, MMP-8,MMP-9, TIMP-1, type I and type III collagen were detected by ELISA. The correlation between MMP-8 and ventricular remodeling indexes was analyzed. Acute myocardial ischemia reperfusion rat models and MMP-8 si RNA lentivirus were established. The animals were divided into control group, ischemia reperfusion group(I/R group), I/R+control-si RNA group, I/R+MMP-8-si RNA group. Observe and record the survival rate 28 d after operation. The changes of heart function were analyzed by M type ultrasonic. Immunohistochemical methods were used to detect myocardial fibrosis. MMP-8 expression in the myocardium after 1, 7, 14, 28 d after operation was detected by Western blot. Localization of myocardial MMP-8 was detected by indirect immunofluorescence. Real-time PCR was used to detect M1 macrophage markers IFN-r, IL-6, TNF-? and M2 macrophage markers CD163,MRC1 and TGF?. Macrophages and fibroblasts of rats were isolated and cultured anddivided into control group, control-si RNA group, MMP-8 si RNA group, respectively.Macrophages were stimulated with LPS(100u M) and IL-4(30u M) 24 h and the changes of M1 and M2 markers were detected by Real-time PCR. Fibroblasts were stimulated with TGF?(10ng/ml) 24 h and ? smooth muscle actin(?-SMA) and fibronectin(FN) were detected by western blot.Results:Left ventricular ejection fraction(EF) decreased significantly after operation compared with that of before operation,with significant differences(P<0.05);LVESD and LVEDD increased significantly(P< 0.05), left ventricular wall thickness(LVAWT) of ventricular wall thickness and left ventricular posterior wall thickness(LVPWT) decreased significantly after operation compared with that before operation(P < 0.05).MMP-2 and MMP-9 significantly increased when STEMI compared with control group(P< 0.05); MMP-2 and MMP-9 further increased after PCI compared with that before operation(P<0.01). In contrast, TIMP-1 significantly decreased when STEMI compared with control group(P< 0.05); TIMP-1 further decreased after PCI compared with that before operation(P<0.01).Type I collagen significantly increased when STEMI compared with control group(P<0.05); it further increased after PCI compared with that before operation(P<0.05). Type III collagen increased when STEMI and increased further after PCI, but without significant differences(P>0.05).MMP-8 significantly increased when STEMI compared with control group(P< 0.05);after 24 h after operation, MMP-8 increased further but without significant differences compared with that before operation( P > 0.05). And 3 months after operation,MMP-8 increased significantly compared with that before operation(P < 0.05).Before operation and after 3 months after operation, MMP-8 was negatively correlated with left ventricular EF(r=-0.458, P<0.05); MMP-8 were positively correlated with LVESD and LVEDD(r=0.54, P<0.05; r=0.423, P < 0.05); MMP-8was negatively correlated with LVPWT and LVAWT(r=-0.627, P < 0.05; r=-0.716, P< 0.05). 28 d after operation, the survival rate of control group, I/R group,I/R+control-si RNA, I/R+ MMP-8- si RNA group was 100%, 50%, 50% 80%,respectively. The survival rate in I/R+ MMP-8-si RNA group significantly increased compared with I/R group(P < 0.05). 28 d after operation, the increase of body weight in I/R group and control-si RNA was lower than that of MMP-8- si RNA, with significant difference(P<0.05). LVESD and LVEDD in I/R group and I/R+controlsi RNA group increased with significant difference compared with the control group(P<0.05), after MMP-8- si RNA treatment, LVESD and LVEDD reduced significantly compared with I/R group(P<0.05). Similar changes can be seen in left ventricular mass index( LVMI). Myocardial collagen fibers increased significantly in I/R and I/R+control-si RNA group compared with the control group(P<0.01); after MMP-8-si RNA treatment, the collagen fibers reduced significantly compared with I/R group(P < 0.05). MMP-8 protein increased significantly 14 d and 28 days after operation. Compared with 1 day after operation, the difference was statistically(P<0.05; P < 0.01). MMP-8 was not found in cardiac macrophages of control group In I/R group, MMP-8 was detected in macrophages. M1 macrophage markers increased significantly in I/R group, compared with control group(P<0.05; P<0.01). In I/R+MMP-8- si RNA group, M1 macrophage markers reduced significantly compared with I/R group(P<0.05); The changes of M2 macrophage markers were contrast to M1 macrophage markers. After inflammatory stimuli, M1 macrophage markers were significantly more than M2 macrophage markers. After MMP-8 si RNA treatment,M1 macrophage markers decreased significantly compared with the control group(P<0.05, P<0.01). After MMP-8 si RNA treatment, M2 macrophage markers increased significantly compared with the control group(P<0.05, P<0.01). ?-SMA expression was more obvious in the inflammatory stimuli. After MMP-8- si RNA treatment, ?-SMA expression decreased obviously and there was a significant difference compared with the control group(P < 0.05). LN expression was less in the inflammatory stimuli. After MMP-8- si RNA treatment, LN expression increased obviously and there was a significant difference compared with the control group(P <0.05).Conclusions:1.Patients with STEMI after PCI treatment can lead to changes of heart function parameters and ventricular remodeling,2. MMP-2 and MMP-9 increased and TIMP-1 decreased when STEMI and ventricular remodeling, and the ratio between MMPs and TIMP-1 may be involved in ventricular remodeling.3.The balance of extracellular matrix synthesis and degradation is broken during myocardial remodeling, and the collagen fibers increased.4.MMP-8 can be used as one of the indexes of heart function.5. MMP-8 may be involved in STEMI and ventricular remodeling process,providing the basis for clinical target treatment.6. MIRI can cause deterioration of the general condition, body weight and ventricular function.7.Type I and type III collagen of extracellular matrix are involved in MIRI and ventricular remodeling, resulting in deterioration of ventricular function.8.MMP-8 can participate in MIRI and ventricular remodeling. MMP-8 si RNA can reduce the cardiac injury and improve ventricular function.9.Macrophages can secrete MMP-8 and be involved in MIRI and left ventricular remodeling.10.M1 type macrophages is the key type in MIRI. MMP-8 si RNA changes M1 type macrophages polarization and weaken the high inflammatory type, improving to reversing vascular remodeling.11.M1 macrophages are the main type in inflammatory environment.Inhibition of MMP-8 can promote macrophage polarization and convert into M2 type macrophages, thereby weakening the high inflammatory status.12. MMP-8 si RNA can inhibit fibroblast differentiating into muscle fibroblast and reduce ventricular remodeling. |
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