C.-Q. Xu’s research while affiliated with Harbin Medical University and other places

Aim: To observe the protective effect of quercetin on rat cardiomyocyte apoptosis induced by adriamycin and explore its possible mechanism. Methods: Cultured neonatal rat cardiomyocytes were randomly divided into six groups: normal control group, adriamycin group, quercetin control group, adriamycin + quercetin (25,50,100 μmol·L-1) groups. The activity of LDH was detected by chromatometry, the cardiomyocyte viability was measured by MTT, the ultrastructure of cardiomyocyte was observed by electron microscope, the expression of protein Bcl-2 and Bax was analyzed by immunocytochemical, and the mRNA and protein of caspase-3 were detected by RT-PCR and Western blot respectively. Results: Compared with the control group, the activity of LDH was increased but the viability of cardiomyocyte was decreased; the expression of Bax and caspase-3 was up-regulated while Bcl-2 was down-regulated in ADR group. Compared with ADR group, the above changes were lightened in adriamycin + quercetin groups. But the quercetin control group, in which cultured myocardial cells only exposed to quercetin without ADR, had no obvious changes. Conclusions: Quercetin significantly inhibits the apoptosis induced by ADR in the cultured myocardial cells. Its mechanism is involved in the apoptosis-related pathways, including caspase-3, Bax and Bcl-2.

Aim: To observe the protective effect and mechanism of resvera on adriamycin-induced cardiotoxicity. Methods: The cardiotoxicity was induce by adriamycin (ADM) intraperitoneal injection (ip. 15 mg·kg-1). Then the protective effect of pretreatment of resvera on injured cardiomyocyes was observed. Results: Compared with the normal control group, ADM decreased the amplitude of ECG's QRS complex (P < 0.01), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH, levels of NO and MDA in serum, decreased the activity of SOD, and increased the expression of p53 (P < 0.01). Compared with ADM group, 5, 10, 15 mg·kg-1 resvera decreased levels of LDH, NO and MDA, increased SOD activity, recovered the amplitude of QRS complex, decreased the incidence of arrhythmia and p53 expression (P < 0.01 or P < 0.05) in concentration-dependent manner, and lightened the myocardial ultrastructure injury. Resvera showed no significant change on normal mice except increasing the activity of SOD in serum. Conclusion: Resvera had protective effect on adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, inhibiting myocardial lipid peroxidation and apoptosis.

AIM: To elucidate the possible antiarrhythmic mechanism of matrine. METHODS: Whole-cell patch-clamp technique was used to record ionic currents in ventricular myocytes. RESULTS: In guinea pig ventricular myocytes, matrine 100 μmol·L-1 prolonged 90% action potential duration (APD 90) by 40% at a stimulation of 0.1 Hz in a frequency-independent manner, inhibited IK1 by 47% at the test potential of - 120 mV, reduced IKr,tail by 50% and had no effect on IKs,tail. CONCLUSION: Matrine prolonged APD through blockade of multiple potassium currents, which may relate to its antiarrhythmic efficacy.

Objective: To observe the effect of quinidine on sodium current of ventricular myocytes from post-ischaemic rats so as to explore the proarrhythmic mechanisms of quinidine. Methods: The left anterior descending (LAD) coronary artery was ligated to establish the ischemia head model in Wistar rats. Quinidine (10 mg·kg-1·d-1) was administered to rats with coronary occlusion for 3 months. Whole-cell patch clamp techniques were used to record sodium current (INa). Results: The morbidity rate of post-ischemic rats was increased by chronic application of quinidine. At the test potential of - 30 mV, the sodium current amplitude of ventricular myocytes from quinidine-treated group was significantly decreased to - (1284 ± 129) pA from - (1985 ± 204) pA in ischemic group (t = 3.015,P < 0.01). Conclusions: Sodium current was sensitive to quinidine even in post-ischemic heart. The different effects of quinidine on different currents in post-ischemic heart resulted in imbalance of ionic currents of ischemic heart. That may be the ionic mechanism of proarrhythmic effect of chronic application of quinidine.

Background: Dysfunction induced by free radicals is the major cause of ischemic diseases of the heart, bowel, liver, kidney, and brain. It is a hot topic to develop drugs which can prevent cells from damages caused by free radicals. Objective: To study the protective effect of safflower yellow pigment (SYP) on the electrophysiological abnormality induced by oxygen derived free radical in single guinea pig ventricular myocytes. Design: Non-randomized case control study. Settings, participants and interventions: This study was completed in Department of Pharmacology of Harbin Medical University. A total of 30 guinea pigs were selected without considering gender. The single ventricle myocyte before intervention was used as normal control. Exogenous oxygen-derived free radicals (1 mmol/L of H2O2) were given to single ventricle myocyte of guinea pig when SYP(3.3 μg/L) was given in advance. Main outcome measure: Whole-cell patch clamp techniques were used to record action potential duration (APD), L-type calcium current (ICa) and inward rectifier potassium current(Ik1). Results: H2O2(1 mmol/L) led to the damage of ventricle myocytes of Guinea pig which was presented by decrease of action potential duration. The APD50 and APD90 were shortened from (331.2 ± 31.9) ms and (380.8 ± 28.2) ms to (169.5 ± 76.0) ms and (238.4 ± 21.3) ms (n = 8, t = 3.834, P < 0.01 ) respectively. Pretreatment with SYP(3.3 μg/L) could markedly attenuate the injury effect of H2O2 on APD; H2O2 significantly inhibited L-type calcium current (ICa) from (- 1 023.45 ± 74.34) pA to (- 275.21 ± 38.67) pA (n = 6, P < 0.001) at the test potential 10 mV. H2O2 also inhibited inward rectifier potassium current of normal group from (-2 133.5 ± 570.4) pA to(- 567.0 ± 218.0) pA at the test potential of - 120 mV. Although the inhibitory effects on L-type ICa of ventricle myocytes for ten minutes, which caused by exogenous oxygen-derived free redicals could be improved, the effect of H2O2 on IK1 could not be changed. Conclusion: SYP can antagonise the damage induced by free radical. It suggests that free radical can be cleared away by SYP. This study provides the mechanical basis for the treatment of ischemic heart disease and invention of rehabilitation.

The paper described a limited part of the coagulation pathway, and in particular the inhibitory effects of activated protein C in the context of thrombin production. This is a computational modeling study with various assumption made of kinetic rates laws and their summation. The level of complexity and assumed parameters makes conclusions uncertain. However, an interesting outcome is that kinetic reaction rates may show oscillation behavior under particular, high levels of protein C feedback inhibition. The model would defy quantitative practical use, but could have predictive value as a qualitative descriptor of coagulation.

OBJECTIVE: To observe the effect of oxymatrine on intracellular calcium concentration ([Ca2+]i) in freshly isolated ventricular cell of guinea pig. METHODS: An enzymatic method was used to isolate single cardiomyocyte of guinea pig. The isolated cardiomyocyte was placed in Tyrode solution containing Ca2+ 1.8 mmol·L-1 or Ca 2+-free solution containing EGTA 2 mmol·L-1 and loaded with Ca2+-sensitive fluorescent indicator Fluo-3/AM. [Ca 2+]i represented by fluorescent intensity (FI) was measured by laser scanning confocal microscope (LSCM). RESULTS: At resting levels, [Ca2+]i was not affected by 10 μmol·L-1 oxymatrine. However, 10 μmol·L -1 oxymatrine obviously inhibited the Ca2+ influx induced by KCl 60 mmol·L-1 (P < 0.05). CONCLUSION: Oxymatrine showed significant inhibition of voltage-dependent channel (VDC), which may be one of the mechanisms of counteracting arrhythmia.

In plastics, people hope that the conventional expansion be replaced by rapid expansion, because expanded period could be shortened greatly. Also people are concerned at whether skin properties after rapid expansion approach that after conventional expansion. A comparison of skin biomechanical properties in vitro was carried out. Biomechanical properties in vitro, such as tensile strength, stress-strain, stress-relaxation, and creep were tested by INSTRON material testing machine. Results showed that the biomechanical properties of experimental specimens differed significantly from those of their controls immediately after expansion, however, the difference reduced with time. With the same maintenance period, the biomechanical properties of rapidly expanded skin were similar to those of the conventionally expanded skin. The conclusion is that rapid skin expansion dose not exhibit any deleterious effect when compared with the conventional expansion. Extension at the maintenance period could improve the biomechanical properties of expanded skin. Therefore, rapid expansion with an extended maintenance period is acceptable in clinical practice.