Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Protective effect of trimetazidine on myocardial free radical inj ury induced by pirarubicin / 吉林大学学报(医学版)

Objective To explore the effects of trimetazidine on myocardial free radical inj ury induced by pirarubicin,and to clarify the protective effect and mechanism of trimetazidine on myocardial inj ury induced by pirarubicin.Methods 3 6 Wistar rats were randomly divided into pirarubicin group (n= 1 3 ), trimetazidine intervention group(n=13)and control group (n=10).The rats in pirarubicin group and trimetazidine intervention group were inj ected with pirarubicin 2.5 mg · kg-1 by the vena caudal once a week for 6 weeks. The rats in trimetazidine intervention group were intragastricly infused with trimetazidine 5.4 mg · kg-1 · d-1 one day for 8 weeks before making the model. At the end of the experiment,the malonaldehyde (MDA)level,nitrogen oxide (NO)level,superoxide dismutase(SOD)activity,and nonprotein sulfhydryl (NPSH)level in myocardium tissue were measured. The histological changes of myocardium tissue were detected by electron microscope. Results Compared with control group ,the levels of MDA and NO in pirarubicin group were increased(P<0.05), and the SOD activity and NPSH level in pirarubicin group were decreased(P<0.05).Compared with pirarubicin group,the levels of MDA and NO in trimetazidine intervention group were decreased(P<0.05),the SOD activity and NPSH level in trimetazidine intervention group were increased(P<0.05).Under electron microscope,the myocardiocytes of the rats in pirarubicin group showed irregular arrangement in sacromere structure, shrinkage in nuclear membrane, vacuolation in nuclear matrix, obvious mitochondria swelling, deposition of metachromatin throughout the nucleus,and an indistinct view of intercalated disc with isolation;while in trimetazidine intervention group the nucleus was round and nuclear membrane was indented,myofilament bundles were decreased slightly with a regular arrangement, intercalated disc oriented transversely with partial vague in cell j unction structure, and mitochondria slightly swelled.Conclusion Trimetazidine has the protective effects on the damaged myocardiocytes caused by pirarubicin,and its mechanism may be related to reducing the production of free radicals and decreasing the injury of structures within the cells,such as the nucleus,mitochondria and intercalated disc.

Ischemia-reperfusion injury induced overexpression of autophagy-related genes in cardiomyocytes / 第二军医大学学报

Objective: To investigate the effect of ischemia-reperfusion (IR) injury on the expression of autophagy-related gene in cardiomyocytes. Methods: Male adult SD rats, weighing 250-300g, were randomly divided into 2 groups, namely, the control group, in which rats underwent thoracotomy without left anterior descending coronary (LAD) ligation, and IR group, in which the left anterior descending coronary arteries were ligated for 45 min, followed by reperfusion for 2 h. Beclin 1 and Atg5 mRNA expression levels were examined by RT-PCR in the myocardium, and the LC3 protein was determined by Western blotting analysis. Results: Beclin 1 and Atg5 mRNA expression levels in IR group increased to 2.45 and 1.6 times those of the control group, respectively (P<0.05). The expression of LC3-II protein was increased, which led to significant increase of LC3-II/LC3-I ratio in IR group (1.4 vs 0.2, P<0.01). Conclusion: Ischemia-reperfusion injury can induce expression of Atg family, promoting autophagy and causing cardiomyocyte damage.

Influence of collagenase with different degrees of activity on the isolation of rats' myocardiocytes / 解放军医学杂志

Objective To investigate the influences of 4 kinds of collagenase with different degrees of activity on the survival rate,contraction and relaxation functions of isolated rats' myocardiocytes.Methods Rats' myocardiocytes were isolated by enzymolysis with 4 kinds of collagenase with different degrees of activity.The survival rate of myocardiocytes was observed immediately after isolation(D),one hour after loading with calcium(E time point) and 10 minutes after electric stimulation(F time point).The contraction and relaxation functions of myocardiocytes,including contraction amplitude(ph),the proportionality of ph/single cardiocyte length(bl),maximal velocity of contraction(+dL/dt) and maximal velocity of relaxation(-dL/dt),were measured with IonOptix video edge tracker.Results From 203U/mg to 299U/mg,with lowering of the activity of collagenase,the isolation time became longer,the survival rate of myocardiocytes declined 1 hour after loading calcium and 10 minutes after electric stimulation(P

Effect of ropivacaine on ion channels in isolated cardiomyocytes of guinea pig / 中华麻醉学杂志

0 05) Conclusion The cardiotoxicity of ropivacaine is related to the inhibition of sodium and calcium channels

Study on antioxidant effect of Astragalus polysaccharide / 中国药理学通报

Xanthine-Xanthine oxidase ( X-XOD) added to the culture medium of cultured cardiac cells in rats may damage cell membrane. Electrophysiological findings indicated that APA, MDP, OS,Vmax, were decreased and the SDF was increased. Astragalus polysaccharide (APS) could protect the cells from being damaged by X-XOD. APS recoverted all the de-creased cardiac functional parameters in free-radical-damaged rats by X-XOD. APS had anti-free-radical damage action on the cultured my-ocardiocytes and the myocardial contractility of the isolated rat working heart.