1.Effects of acute mixed hyperlipidemia on acute myocardial infarction size and its mechanism
Hong CHEN ; Ruojie WANG ; Jingyi REN ; Bei WU ; Lijun LI
Journal of Peking University(Health Sciences) 2004;0(03):-
Objective:To investigate the effect of acute mixed hyperlipidemia on acute myocardial infarct size and the potential mechanism.Methods: Fifty-three Sprague-Dawley(SD) rats were divided into three groups: the control group(n=15) was injected with 1.0 mL 0.9% sodium chloride,the low dose group(n=17) and high dose group(n=21) were injected with 0.5 mL and 1.0 mL 10% Triton WR-1339 solution respectively.Acute myocardial infarction was produced 24 hours after the injection.Serum lipid and the activity of lipoprotein-associated phospholipase A2(Lp-PLA2) were measured before and 24 hours after the injection.Rats were killed 24 hours after ligation and their hearts were excised to evaluate the myocardial infarct size.Results: Serum total cholesterol(TC) and trig1ycerides(TG) concentrations were(6.92?1.48) mmol/L and(11.76?2.76) mmol/L in the low dose group 24 hours after injection,(11.91?0.87) mmol/L and(33.97?5.85) mmol/L in the high dose group,and both increased significantly compared with the baseline.Also serum low density lipoprotein cholesterol(LDL-C) concentration increased(P0.05).Myocardial infarct size was significantly(P
2.Establishment and Evaluation of Mouse Model of Pregnancy Pain-depression Comorbidity Induced by Chronic Unpredictable Stress, Complete Freund's Adjuvant and Formalin
Yisu ZHANG ; Xinru LIU ; Ruojie WU ; Rui LIU ; Hong OUYANG ; Xiaohong LI
Laboratory Animal and Comparative Medicine 2024;44(3):259-269
Objective To establish a mouse model of pregnancy pain-depression comorbidity induced by chronic unpredictable stress (CUS), complete Freund's adjuvant (CFA), and formalin, and to systematically evaluate the associated phenotypes and preliminarily explore the pathological basis of the comorbidity.Methods Eight-week-old C57BL/6J female mice were randomly strarified divided into a control group (no intervention before pregnancy) and a CUS model group (CUS intervention before pregnancy) based on sucrose preference test (SPT) data. After completing the CUS treatment, female and male mice were paired and mated. Pain was induced by injecting 50% CFA and 5% formalin in the right hind foot during pregnancy to create a model of pregnancy pain-depression comorbidity. The experiment was divided into 8 subgroups: control-blank group, CUS-blank group, control-CFA group, CUS-CFA group, control-formalin group, CUS-formalin group, control-CFA+formalin group, and CUS-CFA+formalin group, with 10 mice in each group. The mice in each group were subject to behavioral tests, including the SPT, forced swimming test, tail suspension test, and open field test before and after CUS intervention, during pregnancy, and after delivery. Pain sensitivity changes were measured using mechanical allodynia and thermal hyperalgesia tests. Mice were then euthanized. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in hippocampus, as well as cortisol and adrenocorticotropic hormone (ACTH) in serum, were detected by enzyme-linked immunosorbent assay (ELISA).ResultsCompared with the control-blank group, the CUS-blank group showed a significant depression-like behavior with reduced pain threshold (P<0.001). The control-CFA+formalin group showed a decrease in pain threshold after both CFA injection and formalin injection (P<0.01). Compared with the control-blank and control-formalin groups, the pain threshold was significantly lower in the CUS-formalin group (P<0.01), with a sequential decrease among the three. Compared with the control-blank and control-CFA groups, the pain threshold was significantly lower in the CUS-CFA group (P<0.001), with a sequential decrease among the three. Compared with the control-blank and control-CFA+formalin groups, the mechanical pain threshold of mice in the CUS-CFA+formalin group was significantly lower (P<0.001) and the thermal radiation tolerance time was shorter (P<0.01), both with sequential decreases among the three. Compared with the control-CFA+formalin and the CUS-blank groups, the CUS-CFA+formalin group had a significantly lower percentage of sucrose preference (P<0.001), longer immobility time during the forced swimming test (P<0.001) and tail suspension test (P<0.001), reduced central exploration time in the open field test (P<0.001), reduced total exploration distance (P<0.001), and reduced percentage of distance traveled for central exploration (P<0.001). Compared with the control-CFA+formalin and CUS-blank groups, the serum cortisol and ACTH levels of the CUS-CFA+formalin group were significantly higher (P<0.01), and the levels of IL-6 and TNF-α in the hippocampus were higher (P<0.05).Conclusion The combination of CUS+CFA+formalin injections is an ideal method for establishing a C57BL/6J mouse model of pregnancy pain-depression comorbidity. The behavioral changes in model mice may be attributed to the regulation of inflammatory response in hippocampus and hormone levels in the hypothalamic-pituitary-adrenal (HPA) axis.