Impact of adipokine metabolism on coronary microvascular dysfunction and clinical application value of Shexiang Tongxin dropping pills
10.16781/j.CN31-2187/R.20240008
- VernacularTitle:脂肪因子代谢对冠状动脉微血管功能障碍的影响及麝香通心滴丸的临床应用价值
- Author:
Yuanhao WU
1
;
Yanjun LIN
;
Hongliang FU
;
Shu MENG
Author Information
1. 上海交通大学医学院附属新华医院临床医学院,上海 200029
- Keywords:
microvascular dysfunction;
coronary artery;
Shexiang Tongxin dropping pills;
leptin;
adipokine metabolism;
anti-inflammation
- From:
Academic Journal of Naval Medical University
2024;45(10):1250-1258
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the impact of adipokine metabolism on coronary microvascular dysfunction(MVD)and the clinical application value of Shexiang Tongxin dropping pill(STDP).Methods From Sep.2018 to Dec.2019,41 patients with coronary heart disease in Department of Cardiology,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled and divided into non-MVD group(20 cases)and MVD group(21 cases);29 MVD patients were randomly divided into basic treatment group(14 cases)and STDP group(15 cases)with basic treatment or additional STDP treatment for 3 months;and the patient's complaints,blood biochemical indicators,expression levels of plasma inflammatory factors and adipokines were analyzed.A myocardial ischemia-reperfusion model was established in male C57BL/6 mice aged 12-14 weeks.Mice were divided into sham operation group,ischemia-reperfusion(IR)group(normal saline gavage),and IR+STDP group(STDP gavage),with 5 mice in each group.The levels of plasma inflammatory factors were measured by enzyme-linked immunosorbent assay,the microvascular occlusion of the heart tissue was measured by thioflavin-S staining,and the differential expression proteins between the IR group and IR+STDP group were explored by proteomics analysis and verified by Western blotting.Results Compared with the non-MVD group,the MVD group showed a significant increase in plasma leptin level([9.89±2.42]μg/L vs[4.76±1.02]μg/L,P<0.01),a significant decrease in adiponectin level([5.02±1.3]pg/mL vs[7.19±1.76]pg/mL,P<0.05),and a significant increase in resistin level([9.20±2.03]μg/L vs[5.70±1.32]μg/L,P<0.05).Pearson correlation analysis showed a positive correlation between leptin levels and MVD(r=0.82 and P<0.01).Receiver operating characteristic curve analysis showed that the area under curve value of plasma leptin was 0.855(sensitivity 0.714,specificity 0.867,and optimal cutoff value>9.395 μg/L).After 3 months of treatment,compared with the basic treatment group,the improvement rates of symptoms of chest distress and chest pain in the STDP group were significantly higher(73.3%[11/15]vs 21.4%[3/14]),and the levels of plasma leptin,interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were significantly lower([11.36±0.54]μg/L vs[12.12±0.85]μg/L,[3.96±1.76]pg/mL vs[8.65±1.29]pg/mL,[24.82±3.07]ng/mL vs[32.45±3.32]ng/mL,all P<0.05).In animal studies,compared with the IR group,the mice in the IR+STDP group showed a 45%reduction in no-reflow area(P<0.01)and a 23%reduction in low-reflow and no-reflow areas(P<0.05)after myocardial ischemia-reperfusion;the expression levels of IL-6 and TNF-α were significantly decreased([378.25±19.66]pg/mL vs[457.32±32.01]pg/mL,[289.71±47.62]pg/mL vs[371.28±41.05]pg/mL,both P<0.05).Proteomic analysis showed that the expression levels of von Willebrand factor(vWF)and intercellular cell adhesion molecule-1(ICAM-1)in the cardiac tissue of mice in the IR+STDP group were significantly lower than those in the IR group.Western blotting results also showed that the expression levels of vWF and ICAM-1 in the IR+STDP group were significantly lower than those in the IR group(both P<0.01).Conclusion MVD patients have abnormal adipokine metabolism and high plasma leptin.STDP can improve clinical symptoms of MVD patients,reduce the plasma leptin level and inflammatory indicators,and the mechanism may be related to its antiplatelet and anti-inflammatory effects.