| Backgroud Atherosclerosis (AS) disease is seriously harmful to human health, Coronary atherosclerotic heart disease accounted for a higher proportion. Before the occurrence of coronary atherosclerosis, coronary microvascular lesions has appeared. AS coronary microvascular lesions has become a research hotspot, but the mechanisms has not been reported.Objective To explore the protective effect and mechanism of Guizhi Fuling Capsule on coronary microcirculation in AS Sprague-Dawley (SD) rats. To provide the research materials for coronary microvascular lesions in clinical detection and Guizhi Fuling Capsule in the further clinical application.Methods Fifty healthy male Sprague-Dawley rats were randomly divided into two groups:normal group (administered with ordinary diet, n=12), atherosclerosis (AS) model group (established by high cholesterol diet and intraperitoneal injecting Vit D3, n=38). Two rats of each group were killed randomly at the8th weekend. To detect the serum lipids and observe the morphological of the thoracic aorta pathology specimens, and confirm the AS model has been copied successfully. Then the AS model group will be given by half of the high cholesterol diet. AS model group was randomly divided into3groups:AS group (group B, administered with normal saline at the daily dose of8mL/kg by gastrogavage, n=12), control group(group C, administered with equal simvastatin and captopril at the daily dose of0.86mg/kg and4.3mg/kg by gastrogavage, n=12), trentment group (group D, administered with equal Guizhi Fuling Capsule at the daily dose of0.24g/kg by gastrogavage, n=12).Normal group (group A, n=10). All the rats were killed at the14th weekend. Using Hematoxylin and eosin staining method to observe the formation of pathological change in thoracic aortia. The tissue of left ventricular perpendicular to the long axis of1/3rat was taken to detect the changes of the microvessel density and the protein expression of Matrix metalloproteinase-2(MMP-2), Tissue inhibitor of metalloproteinas-2(TIMP-2), Nuclear transcription factor kappaB (NF-κB) in myocardium by immunohitochemical method. MMP-2, TIMP2and NF-κB mRNA expression in myocardium were detected using reverse transcription-polymerase chain reaction (RT-PCR).Results1. The aorta of normal group rats showed smooth, complete and no pathological changes under light microscope. The atheromatous plaques could be found in the vessel wall of AS group. They consists of a large number of collagen fibers and smooth muscle. The foam cells, inflammatory cells, smooth muscle cells, and other substances could be found under the fibrous cap. Only a small amount of endothelial in the blood vessel wall shed in the treatment group and the control group.2. Compared with normal group, control group and treatment group, the density of microarteries in myocardium in AS group significantly increased with statistical difference (P<0.05). Compared with normal group, AS group and control group, the density of capillaries in myocardium in treatment group increased, showing statistical difference (P<0.05). Compared with normal group and control group, the density of microarteries in myocardium in AS group significantly decreased with statistical difference (P<0.05). There was no statistical difference in the rest comparison (P>0.05).3. Compared with normal group, control group and treatment group, MMP-2and NF-κB expression in myocardium in AS group significantly increased with statistical difference (P<0.05). Compared with normal group and control group, NF-κB expression in treatment group significantly decreased with statistical difference (P<0.05). Compared with normal group, AS group and control group, TIMP-2expression in treatment group increased, showing statistical difference (P<0.05). Compared with AS group and control group, TIMP2expression in normal group significantly decreased with statistical difference (P<0.05). There was no statistical difference in the rest comparison (P>0.05).4. The expression of MMP-2、NF-κB in AS rats was negatively correlated with the density of capillaries in myocardium (r<0, P<0.05), and was positively correlated with the density of microarteries in myocardium (r>0, P<0.05). The expression of MMP-2was positively correlated with the expression of NF-κB (r>0, P<0.05) in myocardium. The density of microarteries was negatively correlated with the density of microarteries in myocardium (r<0, P<0.05).Conclusions1. The expression of MMP-2、NF-κB in myocardium of AS rats will increase. It could decrease the density of capillaries and increase the density of microartery in myocardium. Thereby the structure and function of coronary microcirculation would be destroyed.2. The expression level of MMP-2of AS rats in myocardium is positively correlated with the expression level of NF-κB. Both them can promote each other to affect myocardium microcirculation.3. Guizhi Fuling Capsule could protect the coronary micro vessels and improve coronary microcirculation by regulate the expression of MMP-2、TIMP-2、NF-κB in myocardium. |
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