1.Study on the modeling method of rat model of coronary heart disease complicated with depression"double heart"disease
Fangge LU ; Yaxi LU ; Ge WU ; Ping YANG ; Qian WANG ; Yangyu PAN ; Yanna LUO ; Chengxiang WANG ; Pengyun KONG ; Liqiang YANG ; Xiaohong LI
Chinese Journal of Comparative Medicine 2025;35(7):11-24
Objective To observe the effects of four different modeling method on the hypothalamus-pituitary-adrenal(HPA)axis,blood rheology,platelet aggregation rate,and myocardial ischemia in rats,and to provide new ideas for the establishment of a rat model of"double heart"disease in line with clinical diagnosis and treatment characteristics.Methods Sixty-nine male Sprague-Dawley rats were divided randomly into a Control group(unstimulated),chronic unpredictable mild stimulation(CUMS)group,isoproterenol(ISO)group(intraperitoneal injection of ISO),high-fat diet(HFD)group(fed high-fat chow),and composite model(CUMS+ISO+HFD)group(n=12 rats in the Control and HFD groups;n=15 rats in the other three groups,respectively).Modeling procedures were carried out for a total of 8 weeks,with ISO injection started from week 6 of the experiment for a total of 3 weeks.At the end of modeling,rats in each group were subjected to absent-field and sugar-water preference behavioral tests.Electrocardiography(ECG)was performed to observe changes in ECG lead Ⅱ in each group.Serum levels of adrenocorticotropic hormone(ACTH),cortisol(Cor),corticosterone(CORT),endothelin-1(ET-1),and soluble intercellular adhesion molecule-1(sICAM-1)were detected by enzyme-linked immunosorbent assay.Myocardial histopathological changes were detected by hematoxylin/eosin(HE)staining.Serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an enzyme labeling instrument.Whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were assessed using an automatic blood rheology analyzer.The maximum platelet aggregation rate(MAR)and average platelet aggregation rate(AAR)induced by arachidonic acid and adenosine diphosphate were detected using a whole-blood platelet aggregometer.Results Compared with the Control group,all four model groups had significantly lower absenteeism distance and number of entries into the central region in the absent-field test,and a lower sugar-water preference ratio(P<0.01).ECG revealed ST-segment elevation in the ISO and CUMS+ISO+HFD groups,tachycardia in the CUMS group,and mild ST-segment elevation in the HFD.Serum ACTH,Cor,CORT,ET-1,and sICAM-1 were all significantly elevated in the four model groups(P<0.01).HE staining showed that myocardial tissue was severely damaged in rats in the ISO and CUMS+ISO+HFD groups,with pathological changes such as localized fibrosis and inflammatory infiltration of the myocardium,while mild cardiomyocyte disarrangement and fracture was seen in the CUMS and HFD groups.Rats in the HFD group had increased serum TC and LDL(P<0.01)and decreased HDL contents(P<0.01).Compared with the Control group,whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were all increased in the CUMS,HFD,and CUMS+ISO+HFD groups(P<0.01,P<0.05),while whole blood high-cut viscosity(200 V/S),whole blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen levels were decreased in rats in the ISO group(P<0.01,P<0.05).MAR and AAR were significantly higher in rats in the CUMS,HFD,and CUMS+ISO+HFD groups(P<0.01),while the platelet aggregation rate was decreased in the ISO group compared with the Control group(P<0.01,P<0.05).Conclusions These result showed that the rat CUMS+ISO+HFD model better reflected the complexity of clinical double heart disease than the other three models.
2.Study on the modeling method of rat model of coronary heart disease complicated with depression"double heart"disease
Fangge LU ; Yaxi LU ; Ge WU ; Ping YANG ; Qian WANG ; Yangyu PAN ; Yanna LUO ; Chengxiang WANG ; Pengyun KONG ; Liqiang YANG ; Xiaohong LI
Chinese Journal of Comparative Medicine 2025;35(7):11-24
Objective To observe the effects of four different modeling method on the hypothalamus-pituitary-adrenal(HPA)axis,blood rheology,platelet aggregation rate,and myocardial ischemia in rats,and to provide new ideas for the establishment of a rat model of"double heart"disease in line with clinical diagnosis and treatment characteristics.Methods Sixty-nine male Sprague-Dawley rats were divided randomly into a Control group(unstimulated),chronic unpredictable mild stimulation(CUMS)group,isoproterenol(ISO)group(intraperitoneal injection of ISO),high-fat diet(HFD)group(fed high-fat chow),and composite model(CUMS+ISO+HFD)group(n=12 rats in the Control and HFD groups;n=15 rats in the other three groups,respectively).Modeling procedures were carried out for a total of 8 weeks,with ISO injection started from week 6 of the experiment for a total of 3 weeks.At the end of modeling,rats in each group were subjected to absent-field and sugar-water preference behavioral tests.Electrocardiography(ECG)was performed to observe changes in ECG lead Ⅱ in each group.Serum levels of adrenocorticotropic hormone(ACTH),cortisol(Cor),corticosterone(CORT),endothelin-1(ET-1),and soluble intercellular adhesion molecule-1(sICAM-1)were detected by enzyme-linked immunosorbent assay.Myocardial histopathological changes were detected by hematoxylin/eosin(HE)staining.Serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured using an enzyme labeling instrument.Whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were assessed using an automatic blood rheology analyzer.The maximum platelet aggregation rate(MAR)and average platelet aggregation rate(AAR)induced by arachidonic acid and adenosine diphosphate were detected using a whole-blood platelet aggregometer.Results Compared with the Control group,all four model groups had significantly lower absenteeism distance and number of entries into the central region in the absent-field test,and a lower sugar-water preference ratio(P<0.01).ECG revealed ST-segment elevation in the ISO and CUMS+ISO+HFD groups,tachycardia in the CUMS group,and mild ST-segment elevation in the HFD.Serum ACTH,Cor,CORT,ET-1,and sICAM-1 were all significantly elevated in the four model groups(P<0.01).HE staining showed that myocardial tissue was severely damaged in rats in the ISO and CUMS+ISO+HFD groups,with pathological changes such as localized fibrosis and inflammatory infiltration of the myocardium,while mild cardiomyocyte disarrangement and fracture was seen in the CUMS and HFD groups.Rats in the HFD group had increased serum TC and LDL(P<0.01)and decreased HDL contents(P<0.01).Compared with the Control group,whole-blood high-cut viscosity(200 V/S),whole-blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen were all increased in the CUMS,HFD,and CUMS+ISO+HFD groups(P<0.01,P<0.05),while whole blood high-cut viscosity(200 V/S),whole blood low-cut viscosity(10 I/S),plasma viscosity,and fibrinogen levels were decreased in rats in the ISO group(P<0.01,P<0.05).MAR and AAR were significantly higher in rats in the CUMS,HFD,and CUMS+ISO+HFD groups(P<0.01),while the platelet aggregation rate was decreased in the ISO group compared with the Control group(P<0.01,P<0.05).Conclusions These result showed that the rat CUMS+ISO+HFD model better reflected the complexity of clinical double heart disease than the other three models.
3.Echocardiographic assessment of cardiac systolic function in patients with systemic lupus erythematosus using non-invasive pressure-strain loop
Yilu SHI ; Ning TIE ; Shasha DUAN ; Yaxi WANG ; Wuping XIAO ; Haiyue ZHAO ; Lu ZHANG ; Minjie ZHANG ; Xiaoshan ZHANG
Chinese Journal of Ultrasonography 2022;31(10):852-858
Objective:To observe the feasibility of evaluating right ventricular (RV) function by the method based on left ventricle (LV) pressure-strain ring (PSL) technique in patients with systemic lupus erythematosus (SLE), and to evaluate the efficacy of non-invasive PSL in the diagnosis of dysfunction of both LV and RV.Methods:Thirty-nine patients were enrolled with SLE who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from March 2020 to September 2021 and 57 sex- and age-matched healthy controls underwent assessment by conventional echocardiography, two-dimensional speckle tracking imaging (2D-STI) and myocardial work (MW). The echocardiographic parameters were compared between the groups. The correlations between RVMW parameters and conventional echocardiographic parameters, and between MW parameters and SLEDAI-2K score were analyzed by Spearman correlation analysis.Results:①The two groups did not show any difference at the conventional echocardiographic parameters of the LV systolic function ( P>0.05). In the SLE group, tricuspid regurgitation maximal velocity (TR V max) and right ventricular index of myocardial performance (RIMP) increased, tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular S′ (S′ tv) decreased (all P<0.05), and others did not show statistical difference (all P>0.05). ②The 2D-STI parameters: There were no significant differences in left ventricular global longitudinal strain (LV GLS) ( P>0.05), however RVGLS decreased ( P<0.05). ③The MW parameters of LV and RV: including global constructive work (GCW), global work index (GWI), global wasted work (GWW), and global work efficiency (GWE). In SLE group, LV GWE, RV GWE decreased and LV GWW, RV GWW increased ( P<0.05), others were no significant differences ( P>0.05). ④The correlation analysis: RV GWI positively correlated with TR V max ( rs=0.481). RV GCW positively correlated with TR V max ( rs=0.587). RV GWW positively correlated with right atrial area (RAA) and TR V max ( rs=0.429, 0.610), negatively correlated with S′ tv ( rs=-0.342). RV GWE positively correlated with S′ tv ( rs=0.326) and negatively correlated with RAA ( rs=-0.462) (all P<0.05). SLEDAI-2K score was negatively correlated with LV GLS ( rs=-0.333) and LV GWI ( rs=-0.326) ( P<0.05). Conclusions:The study has shown the impaired systolic function of both LV and RV in patients with SLE. PSL technique, especially RVMV based on LV PSL technique might emerged as a novel measure to evaluate systolic dysfunction in SLE patients.
4.Progress in pathogenesis of autoantibody-related congenital heart block
Tianhao BAI ; Shasha DUAN ; Yaxi WANG ; Yilu SHI ; Lu ZHANG ; Haiyue ZHAO ; Xiaoshan ZHANG
Chinese Journal of Perinatal Medicine 2022;25(12):983-986
Autoantibody-related congenital heart block (ACHB) is a passively acquired autoimmune disease developing in fetuses after exposuring to maternal anti-Ro/Sj?gren's syndrome type A (SSA) antibody and/or anti-La/SSB antibody transported across the placenta, which contributes to fetal heart conduction system damage and signal conduction block at the atrioventricular node. However, fetal atrioventricular block does not necessarily occur with the presence of maternal autoantibodies, indicating its complex pathogenesis. This review focuses on the theories of calcium channels and apoptosis, the influence of other maternal factors and environmental changes on ACHB and the roles of natural killer cells and human leukocyte antigen in ACHB, aiming to provide reference for further study on the pathogenesis.
5.Evaluation of cardiac function and systolic dyssynchrony of fetuses exposed to maternal anti-SSA and anti-SSB antibodies using two-dimensional speckle tracking imaging
Shasha DUAN ; Yong WANG ; Yaxi WANG ; Yilu SHI ; Lu ZHANG ; Wuping XIAO ; Xiaoshan ZHANG
Chinese Journal of Ultrasonography 2022;31(4):289-294
Objective:To evaluate the cardiac function and systolic dyssynchrony of fetuses exposed to maternal autoimmune antibodies (anti-SSA/Ro60, anti-SSA/Ro52 and anti-SSB/La) by using two-dimensional speckle tracking imaging (2D-STI).Methods:A total of 52 pregnant women with singleton pregnancy in the Affiliated Hospital of Inner Mongolia Medical University from July 2018 to November 2020 were selected. Eighteen fetuses of mothers with autoimmune antibodies were enrolled as autoimmune disease (AD) group and 34 fetuses of healthy mothers without antibodies were included as control group. Maternal baseline characteristics, fetoplacental Doppler parameters, and conventional echocardiographic data of two groups were prospectively collected. The systolic global and regional longitudinal strain of left and right ventricles (LV and RV) and the time to peak strain of regional myocardium were measured using 2D-STI. The differences in time to peak strain between the LV free wall and RV free wall (two-chamber dyssynchrony, 2C-DYS) and between the septum and LV free wall (one-chamber dyssynchrony, 1C-DYS) were also calculated.Results:There were no significant differences between the two groups in conventional systolic and diastolic functional parameters for the LV and RV(all P>0.05). The myocardial deformation parameters and 2C-DYS obtained by 2D-STI showed no statistical differences between two groups(all P>0.05). However, 1C-DYS was significantly more prolonged in the AD group than control group[28.50(13.50, 39.25)ms vs 19.50(8.00, 29.25)ms, P=0.042]. Conclusions:LV systolic mechanical dyssynchrony in fetuses of mothers with autoimmune antibodies suggests in-utero subclinical damage of the cardiac conduction system.

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