P-p38MAPK And COX-2Expression In Aortic Of Rat Model Of Depression And Hyperlipidemia

BackgroundThe comorbidity of depression and atherosclerosis is increasingly attended. In the depression state, itself disturbance of lipid metabolism and inflammatory mediators may promote occurrence and development of atherosclerosis. Currently, there are few reports about depression and atherosclerosis both relational inflammatory markers and more reports about p-p38mitogen activated protein kinase (phospho-p38MAPK) and cyclooxygenase-2(COX-2) expression in atherosclerosis. But still we know little about p-p38MAPK and COX-2expression in the depressive state, this is the new hot spot to study the comorbidity of depression and atherosclerosis.ObjectiveTo explore p-p38MAPK and COX-2expression in aortic of rat model of depression and hyperlipidemia,and prove that p-p38MAPK and COX-2whether is depression and atherosclerosis relational inflammatory markers, in order to lay the morphological basis for further study of the comorbidity of depression and atherosclerosis.Methods1experimental animal grouping and modeling100SD healthy rats, weight330-480g, adaptively feeding three days, were conducted behavioral score by the openfield test, and selected80rats with similar score, then they were randomly divided into four groups: hyperlipidemia group, depression plus hyperlipidemia group, depression group, the control group with20rats each. The hyperlipidemia group fed high-fat diet; the depression group with chronic unpredictable mild stress (CUMS) stimulus fed basal diet; the depression plus hyperlipidemia group with chronic unpredictable mild stress (CUMS) stimulus fed high-fat diet; the control group fed basal diet. The each group of rats was individually housed.2Evaluation of animal ModelRecorded weight of each group of rats before and after the experiments, used sucrose preference (the sucrose water intake/total fluid intake×100%), the openfield test score and Y-maze score to determine that whether the model was successful.3blood lipids detectionBefore the experiment, the rats were took1.5ml venous blood after8hours of fasting, and the blood was allowed to stand for30minutes at room temperature, then centrifugation15minutes. The serum was stored at4℃, then used enzyme method to measure the level of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterin (LDL-C) and high density lipoprotein cholesterol (HDL-C) in the same day or the next day.4Histopathological stainingEach group of aorta specimens were took out, paraffin embedding, section, and conducted hematoxylin-eosin (HE) staining and resorcinol fuchsin staining; after each group of aorta were took out, liquid nitrogen storage, frozen section, the COX-2and p-p38MAPK immunohistochemistry chromogenic. The two slices were observed with optical microscope.6Statistical methodEach group of the percentage of sucrose preference, openfield test vertical score, openfield test level score, Y-type maze test score, TG, TC, HDL-C, LDL-C and atherogenic index before and after modeling were conducted normality test,(P>0.05),and using the mean±standard deviation(x±s) expression. Paired t-test was used for inferred intra-group before and after modeling comparison; variance analysis was used for inter-group comparison; LSD test was used for pairwise comparisons between groups with using analysis of variance. Used the Image-Pro Plus610graphical analysis software to analyze the results of the COX-2and p38MAPK immunohistochemical staining. Took five slices from each group, and each slice were took two horizons under the microscope with a400-fold, and observed with microscope, and taken figures in a uniform exposure time. Used the Image-Pro Plus610graphical analysis software to determine the average integrated optical density per unit area, and the values were expressed as mean±standard deviation, t-test was used for inter-group comparison, P<0.05was considered that the difference was statistical significance.Results1The experimental rats basic situationAfter120days, rats survived:the control group,20/20; the depression group,19/20; the high-fat group,16/20; the depression plus high-fat group,15/20.2Evaluation of the rat modelCompared with before and after modeling, the percentage of sucrose preference, openfield test vertical score and Y-type maze test score of the depression group and the depression plus hyperlipidemia group had significant difference (P<0.05),and the percentage of sucrose preference openfield test vertical score and Y-type maze test score after modeling were greater than before modeling; the TG, TC, HDL-C, LDL-C and atherogenic index of the hyperlipidemia group and the depression plus hyperlipidemia group had significant difference (P<0.05), after modeling were greater than before modeling. These above results suggested that the model was successful.3Histological change and Immunohistochemical stainingHE staining showed each group without plaque formation, and resorcinol fuchsin stai ning showed that the numbers of elastic fiber layer in depression plus high-fat group, the hi gh-fat group and the depression group significantly increased when compared to control gr oup(P<0.05)while comparisons among depression plus high-fat group, the high-fat group a nd the depression group showed no significant differences.Immunohistochemical staining showed that the p-p38MAPK and COX-2expression of the depression plus hyperlipidemia group, the hyperlipidemia group, the depression group were significantly increased (P<0.05), compared with the control group; the p-p38MAPK and COX-2of the depression plus hyperlipidemia group and the hyperlipidemia group were significantly increased (P<0.05),compared with the depression group; The p-p38MAPK and COX-2of the depression plus hyperlipidemia group was significantly increased (P<0.05), compared with the hyperlipidemia group.Conclusion1Depression can promote blood lipids (LDL-C) and atherosclerosis index (AI) elevated, is an independent risk factor for atherosclerosis.2Depression and hyperlipidemia can increase the p-p38MAPK,COX-2expression associated with atherosclerosis, both are common inflammatory factors of depression and atherosclerosis, and may also be the basis of the comorbidity of depression atherosclerosis.