1.Effect of compound salvae-dropping-pill on intracellular free calcium concentration of cultured rat myocardial cells in case of hypoxia and reoxygenation
Quanfeng LI ; Xiaoming WANG ; Shijun ZHU ; Jing AI ; Huanhuan GAO ; Changqin XU
Chinese Journal of Pathophysiology 2000;0(07):-
AIM: To examine the effect of compound salvae-dropping-pill (CSDP) on intracellular free calcium in cultured rat myocardial cells subjected to hypoxia and reoxygenation.METHODS: The Fluo- 3/AM was applied to probe intracellular calcium concentration and the fluorescent intensity was detected using laser confocal microscopy technique.RESULTS: Fluorescent intensity in hypoxia plus CSDP group was significantly lower (1 217 78?312 07) than that of hypoxia group (1 509?508 48), and the Fluorescent intensity of hypoxia/reoxygenation plus CSDP group was also markedly lower (1 567.91?577 61) than that of hypoxia/reoxygenation group (1 617.60?477.53).CONCLUSION: The cultured rat myocardial cells could be effectively protected by administration of CSDP in case of hypoxia and reoxygenation through decreasing the intracellular calcium concentration. [
2.Protective effect of compound Danshen dripping pills on isolated rat myocardium with anoxin/reoxygenation
Yajun ZHAO ; Congning SHI ; Xiaoming WANG ; Shijun ZHU ; Liying MA ; Xiaoshu JIANG ; Yanping LOU ; Lina WANG ; Quanfeng LI ; Changqing XU
Chinese Journal of Pathophysiology 2000;0(10):-
AIM: The experiment was designed to study the effect of compound Danshen dripping pills (DSDP) on myocardium with anoxin/reoxygenation. METHODS: The myocardial anoxin/reoxygenation model was made in perfused isolated rat heart. DSDP and isosorbide dinitrate (ID) were given at the time of pre-perfusion and reperfusion, then HPLC and H-600 electron microscope were used to detect the change of high energy phosphate and the ultrastructure of myocardial cell. RESULTS: ① The contents of AMP, ADP, ATP and AN in myocardium in only anoxin/reoxygenation group were obviously lower than those in the control group (P0.05). ③ In the groups with ID, the contents of AMP, ADP, ATP and AN were distinctively lower than those in the control group (P
3.Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
ZOU HAI ; ZHANG MENGYU ; YANG XUE ; SHOU HUAFENG ; CHEN ZHENGLIN ; ZHU QUANFENG ; LUO TING ; MOU XIAOZHOU ; CHEN XIAOYI
Journal of Zhejiang University. Science. B 2024;25(9):756-772
Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.