Résumé
BACKGROUND: Resveratrol is a naturally occurring phytoalexin present in grapes, peanut and some herbs. It has been demonstrated to produce a variety of biological actions, such as anticancer, antiinflammation. Accumulating line of evidence supported the view that resveratrol may exert protective effect on cardiovascular system. However, its protective mechanism is not completely understood.OBJECTIVE: To investigate the anti-ischemic effect and mechanism of resveratrol (Res) on acute myocardial infarction in rats.DESIGN: Randomly grouping paralleled control study.SETTING: Pharmacological Laboratory of Harbin Medical University, Biopharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory.MATERIALS: The experiment was carried out in Department of Pharmacology of Harbin Medical University from March 2005 to July 2005.Totally 80 male Wistar rats weighting 250-300 g were selected in this study. Among them, 60 rats after operation successful modeling were randomly grouped into 5 groups: sham operation group, blank control group,resveratrol 5 mg/kg, 15 mg/kg and 45 mg/kg groups with 12 in each group.METHODS: Acute myocardial infarction (AMI) model was induced by ligation of the anterior branch of the left coronary artery in rat, Sham operation group: The same suture was put through but not ligated. Resveratrol group: Rats were injected with 5, 15 and 45 resveratrol mg/kg provided by Hunan Huaguang Biological Products Company Limited (batch number: 20050221, purity ≥99%) and ligated after 10 minutes. Model group: The same volume saline was injected for 10 minutes and then rats were ligated. Observe and record ST segment of standard limb lead Ⅱ electrocardiogram (ECG)after 1, 5, 10, 15, 30 minutes after ligating the left anterior decendingcoronary artery. After 6-hour ischemia, the infarct size areas was identified with the myocardium by 2, 3, 5-triphenyltetrazolium chloride (TTC) stain; the activities of serum .creatine kinase (CK)and lactate dehydrogenase (LDH) were determined by spectrophotometric method; the apoptosis in cardiomyocyte was detected by d-UTP end labeling method mediated with tagged deoxynucleotide transferase in situ (TUNEL); apoptosis-related proteins of Bcl-2, Bax and Fas expression were measured with estreptomicina avidin peroxidase chain. Measurement data were compared with t test.MAIN OUTCOME MEATURES: ST increase; the activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH); the infarct size areas and the apoptosis rate in cardiomyocyte; the. expression of apoptosis-related proteins of Bcl-2, Bax and Fas.RESULTS: All of the 60 rats entered the final analysis. ① ST segment raise in high dosage group was lower than that in model group 1, 5 and 10 minutes after ligation (P ＜ 0.05), and it was also lower than that in model 15 and 30 minutes after ligation (P ＜ 0.05). This effect was dose-dependent. ② Infarct size in each dosage group was smaller than that in model group (P ＜ 0.05). This effect was dose-dependent. ③ The activities of CK and LDH in different dosages of resveratrol groups were significantly lower than those in model group (P ＜ 0.05). This effect was dose-dependent. ④ Apoptosis index in model group was higher than different dosages of resveratrol groups (P ＜ 0.05); The expression levels of Bax and Fas proteins in model group were higher than those in high and middle dosages of resveratrol groups (P ＜ 0.05); The expression level of Bcl-2 protein was lower than that in high and middle dosges of resveratrol groups (P ＜ 0.05).These effects were dose-dependent.CONCLUSION: Resveratrol can protect acute myocardial ischemic injury induced by coronary artery of ligated rats, and the effect is dose-dependent.Effect of resveratrol on myocardial ischemia is related to adjusting expressions of Fas, Bcl-2 and Bax and inhibiting myocardial apoptosis.
Résumé
AIM:To explore the effect of long-term (6 months) endogenous testosterone deprivation by orchidectomy on the function of voltage-dependent potassium channels of vascular smooth muscle cells in rats. METHODS:Wistar rats were raised for 6 months after castration. Isometric tension measurement of aortic rings,whole-cell patch-clamp technique and Western blotting analysis were employed to examine the functional and posttranscriptional alterations of voltage-dependent potassium channels. RESULTS:Voltage-dependent potassium channel blocker,4-aminopyridine,significantly decreased the constriction of aortic artery rings from male rats after 6-month castration. In castrated rats the amplitude of voltage-dependent potassium currents of aortic artery smooth muscle cells was significantly decreased compared with that in control rats. Meanwhile,the expression of Kv 1.5 channel protein,which plays an essential role in mediating vasomotor function,was also reduced. The functional and molecular alterations of voltage-dependent potassium channels were both restored when the rats were concomitant applied with physiological level of testosterone after castration. CONCLUSION:Long-term deprivation of endogenous testosterone in rats significantly attenuates the function of voltage-dependent potassium channels,and the decreases in expression of Kv1.5 channel protein accounts for this alteration. Long-term application of physiological concentration of testosterone,which recovered the impaired function of voltage-dependent channels,may be beneficial for male gender with hypotestosteronaemia.