The Influence Research Of High Salt On Express Of MMP-2and TIMP-2in Atherosclerosis Rats

Objective Exploring the role of high-salt in carotid atherosclerosis (AS) animal model which on the basis of the clamps method; than detecting the change of MMP-2and TIMP-2in the experiment, further discussing the influence of salt in atherosclerosis rats; so as to opening up new ways and means on research, prevention, treatment of atherosclerosis.Materials and methods140male SD rats were randomly divided into four groups, namely the normal control group, normal salt group,6-times salt group, and12-times salt group(except for the normal control group, each group were given the clamp technique of the left carotid artery operation and high fat diet feeding), blood fat detection were done at2nd、6th and10th weekend after operation,and blood pressure detection were done at10th weekend.2On the rat carotid atherosclerosis model, the left injured artery were taken for pathological change observation with the method of HE staining and transmission electron microscope(TEM). The expression and distribution of MMP-2and TIMP-2were examined with the method of immunohistochemistry. The variation of MMP-2mRNA, TIMP-2mRNA were observed by the method of RT-PCR. Statistical analysis:the experimental data were analysed with the SPSS13.0software package, and were presented as mean±standard deviation (plus or minus s). the T-test inspection is used between groups, and ANOVA is used with more than three groups, P<0.05showed statistically significant difference in all cases.Result1Serological and blood pressure observation TC, TG and LDL in normal salt group,6times and12-times salt group were significantly higher than those in normal control grou-p at2nd、6th and10th weekend (P <0.05), also each group serological changes was higher in different periods (P<0.05);the blood pressure were higher than normal control group at10th weekend.2Visual gross observationThe left carotid artery of normal rats were flexible, soft and pink under anesthesia, the luminal was relatively smooth; Except of the normal group, the left carotid artery of each group were slightly uneven thickening, vessel wall were obviously stiff, there were white stripes in the intima.3HE stainingThe vascular wall of Normal rats were smooth and integrity, endothelial cell were without fall off, smooth muscle was in order; The intima of the injured left carotid artery was thickening mildly in normal salt group, a small number of foam cells can be observed here, smooth muscle cells decreased; The intima of the injured left carotid artery was thickening obviously in6-times and12-times salt group, a large number of foam cells can be observed in the prominent fibrous plaque, smooth muscle cells decreased; necrotic material and extracellular lipids were deep here, all those changes formed more mature atherosclerotic plaques.4Artery electron microscope observationThe endothelial cells in normal rats were normal, the endangium were integrated and smooth, the thickness of elastic lamina were equithickness, and the VSMC of tunica media were in order. The endothelial cells falls off more and more and the VSMC of tunica media were more disorder with salt increasing the thickness of elastic lamina out-of-shape were uneven, and the fibrous plaques were here.5Immunohistochemical observationMMP-2and TIMP-2express principally in the cytoplasm of smooth muscle cells, macrophages foam cells in the endarterium, they expressed low level in the normal group, and they expressed higher and higher level in the other groups with the salt content increasing, obviously higher than the normal control group (P<0.05).6RT-PCR observationIn the order of normal control group, normal salt group,6times salt group,12times salt group, The expression of MMP-2and TIMP-2mRNA in carotid artery increased higher and higher (P<0.05).Conclusions1.Blood pressure and lipids increase with the salt concentration increased, indicating that high salt in the fat state allowed it to increased blood pressure and blood lipids is further increased.2the expression of MMP-2,TIMP-2and its gene level gradually strengthened with the salt concentration increased, indicating that there has the dose-effect relationship between their expression and salt with a certain range.3High-salt plays an important role in the establishment of atherosclerosis model, and it is an important factor in the occurrence of AS.