OBJECTIVE:To study the effect and mechanism of cilostazol in experimental anti-bradyarrhythmia.MET-HODS:Bradyarrhythmia model of mice was induced using verapamil hydrochloride and nicotine,respectively.The electrocardiograms at different time and the heart rates of the model mice after intragastric administration of different dosages of cilostazol were recorded.The in vivo His' bundle electrogram(HBE)recordings in rabbits were obtained after intragastric administration of different dosage of cilostazol for detection of A-H interval and H-V interval,which were compared with control group(normal saline group).RESULTS:Verapamil hydrochloride and nicotine markedly slowed down the heart rates of mice,but cilostazol significantly sped up the heart rates in mice(P

Objective To study the effects of potassium channel blocker,tetraethylammonium(TEA) on the proliferation and apoptosis of ovarian cancer cell line SKOV3.Methods SKOV3 cells were treated with TEA.The effect of TEA on proliferation of SKOV3 cells was assessed by MTT assay.Hoechst 33258 fluorescein staining and flow cytometry(FCM) were employed in detection of SKOV3 cells apoptosis.Results TEA(1,5,10 and 20mmol/L) can significantly inhibit the proliferation of SKOV3 cells,the inhibitory rates were 8.61%,18.86%,46.63% and 65.22%,respectively(P

In both clinical and animal experiments,it has been confirmed that the inflammation in heart is involved in the development of heart injury after the ischemia/reperfusion.However,the pro-inflammatory mechanism is extremely complicated.Recently,a growing number of reports indicates that many factors play their roles in the inflammation,such as cytokinemia,inflammatory cells,metabolic product of arachidonic acid and COX et al.They are released/presented in the region of myocardial ischemia/reperfusion and include both ischemic and secondary heart injury.

Aim To observe the neuroprotective effect of sinomenine on hippocampal neurons from injury in-duced by oxygen glucose deprivation ( OGD ) and its underlying mechanism. Methods Hippocampal neu-rons were exposed to OGD for 4 h followed by 24 h re-oxygenation ( OGD-R) . Then cell viability was detec-ted by MTT. LDH release was detected by LDH kit. Cell apoptosis was detected by Hoechst stain. The ex-pression of Bax, Bcl-2 and caspase-3 were detected by Western blot. [ Ca2+] i of hippocampal neurons was detected by calcium imaging. Acid-sensing ion chan-nels ( ASICs ) current was detected by patch clamp technique. Results SN increased cell viability and reduced LDH release. SN also inhibited neuron apop-tosis and increased ratio of Bcl-2/Bax and reduced the expression of caspase-3 . OGD-induced increase of [ Ca2+] i was inhibited by SN. Furthermore, SN inhib-ited ASIC1 a current and also inhibited OGD induced increase of ASICs current in hippocampal neurons. Conclusion SN protects hippocampal neurons against OGD-R-induced injury. The inhibitory effect of SN on ASIC1 a and calcium overload was involved in the pro-tective effect of SN.

Objective To observe the protective effect of total flavone of Camellia (TFC)against cerebral ischemic injury.Methods Decapitation method and close hypoxia method were used to observe the effect of TFC on anoxic tolerance of mice and step down test was used to observe the effect of TFC on learning and memory; after ischemia, the content of malondialdehyde (MDA)and nitric oxide (NO)and the activity of lactate dehydrogenase (LDH)were detected. Rat models with acute incompletely cerebral ischemia were established by means of ligating right common carotid arteries and effect of TFC on cerebral water volume, permeability of cerebral vessels and cerebral histopathological changes were also observed.Results TFC prolonged the grasping time after decapitation and the survival time after anoxia in mice, and improve the learning and memory during the step down test. TFC decreased MDA and NO contents, counteracted the de creases of LDH activities in the mice cerebral cortex, reduced the water volume and permeability of cerebral vessels in ischemic rats and improve the cerebral hitstopathological changes. Conclusion TFC has protective effects against cerebral ischemic injury and the mechanism may be related to the inhibition of free radicals and NO production.

Aim To study protective effects of Total of flacone C(TFC) against cerebral ischemia-reperfusion injury.Methods Four-vessel occlusion method was used to make acute cerebral ischemia-reperfusion model. Rats were initiated by ischemia for 30 min followed by 40 min of reperfusion.The electroencephalography(EEG) during cerebral ischemia and reperfusion was recorded.The level of intracellular calcium ion concentration([Ca~(2+)]i) in cerebral cells after ischemia was measured by using a Ca~(2+) indicator Fura-2/AM.Superoxide dismutase(SOD),Glutathione peroxidase(GSH-Px),Lactate dehydrogenase(LDH),nitric oxide Synthase(NOS) activeties and Malondialdehyde(MDA),Nitric Oxide(NO)contents in the ischemia cerebral cortex were measured.Results TFC can improved the EEG change,significantly attenuated the decrease of the intracellular calcium ion concentration([Ca~(2+)]_i), remarkly increased GSH-Px,SOD and NOS activities in the cerebrum,inhibit the decrease of LDH activity and NO,MDA contents.Conclusion TFC has protective effects on cerebral ischemia-reperfusion injury,the mechanism may be related to attenuating free radical,[Ca~(2+)]i overload and NO.

BACKGROUND: Total flavone of ginkgo biloba(TFG) can affect on free radical, but the effect on apoptosis induced by cerebral ischemia is unclear.OBJECTIVE: To study the inhibitory effect of TFG on apoptosis induced by cerebral ischemia.DESIGN: Completely randomized controlled experimental study based on experimental animals.SETTING: Department of pharmacology in a university.MATERIALS: Totally 24 SD rats in half genders with clean grade and body mass of(250 ± 50) g, were divided into 4 groups at random: sham-operation group, model group, TFG 40 rmg/kg group and TFG 80 mg/kg group (Certificate No. 01).METHODS: This study was completed in the Department of Pharmacology,Anhui Medical University during October 2001 and January 2002. Incomplete cerebral ischemia was made by ligating bilateral common carotid arteries(CCA) in rats. The cerebral injury was evaluated by brain edema. The apoptosis was determined by terminal deoxy-nucleotidyl transforase-mediated dUTP-digoxigenin nick end-labeling(TUNEL) and transmission electron microscopy (TEM) method. The DNA fragmentation analysis was measured with the diphenylamine reagent method.MAIN OUTCOME MEASURES: Major factor: Effect of TFG on ultrastructral alteration of apoptotic cerebral cortex cells; Secondary factor: Effect of TFG on DNA fragmentation induced by cerebral ischemia.RESULTS: Ligating of bilateral CCA markedly induced apoptotic cell in cerebral cortex. TFG 80 mg/kg significantly inhibited brain edema( P ＜ 0.05 )and decreased the numbers of apoptotic cells in cortex( P ＜ 0.01 ) and improved ultrastructral alteration of apoptotic cells; TFG 40, 80 rmg/kg also inhibited the increase of DNA fragmentation induced by cerebral ischemia (P ＜0.05, P ＜0.01).CONCLUSION: TFG has inhibitory effect on ischemia-induced apoptosis of cerebral cortex and improve the ultrastructual changes of apoptosis. Moreover,TFG can relieve the occurrence of edema of ischemic brain tissue and inhibit the increase of DNA section induced by cerebral ischemia.

AIM　To study the role of 5-HT in antinocieption produced by intrathecal indomethacin (Ind) in mice. METHOD　The antinocieption of indomethacin was investigated on the tail immersion test in mice；the contents of 5-HT, 5-HAA were assayed with fluorescent method. RESULT　Dose-dependent antinocieption was observed following intrathecal administration of Ind 1.8 mg*kg-1, the effect could be obliterated when the animals were pretreated with cyproheptadine. After intrathecal administration of Ind, the content of 5-HIAA in the spinal cord of mice was significantly increased, but PG had no effect. CONCLUSION　The result imply that intrathecal indomethacin could produce antinocieption; this effect is mediated by 5-HT. PG does not participate in the action of 5-HT.

AIM: To investigate the protective effects of total of flavone C (TFC) on acute cerebral ischemia in mice and focal cerebral ischemia in rats. METHODS: The occlusion of bilateral common carotid arteries with vagus nerves in mice was used for make the acute cerebral ischemia models. The survival time and the death rate were observed. The permanent occlusion of the proximal of the right middle cerebral artery (MCA) was used for make the focal cerebral ischemia models. The extent of neurological deficits was observed, and the infarct area was measured by NBT staining technique. The activity of LDH and the content of MDA and NO in the ischemic cerebral cortex were determined. RESULTS: TFC of 80 and 40 mg?kg -1 prolonged the survival time and decreased the death rate of mice with acute cerebral ischemia injury. TFC of 60, 30, and 15 mg?kg -1 ameliorated neurologic deficits score and the infarct size of rats with MCAO. CONCLUSION: TFC provides significant protective effects against cerebral ischemia injury.

Aim To explore the effect of pharmacolog-ical activation of serotonin 5-HT2C receptor (5-HT2C R) on naloxone-precipitated withdrawal in morphine-de-pendent mice. Method EthoVision Noldus video tracking system was used to record the effect of 5-HT2C R agonist WAY on locomotor activities and behavioral performances in mice.Results Selective 5-HT2C R ag-onist WAY (0.5,0.75 or 1 .0 mg·kg -1 ,i.p.)a-lone did not alter the locomotor activities as determined by distance traveled and velocity (all P values >0.05).Chronic morphine treatment induced depend-ence in mice as demonstrated by increases in distance traveled,velocity and jumping behavior.WAY (0.5, 0.75 or 1 .0 mg·kg -1 ,i.p.)and clonidine (0.2 mg ·kg -1 ,i.p.)significantly ameliorated naloxone-pre-cipitated withdrawal symptoms,including burrowing, jumping,body grooming,rearing,“wet dog”shakes, head shakes,face grooming,penile grooming,scratch (all P values <0.05).Conclusion Pharmacological activation of 5-HT2C R ameliorates naloxone-precipitated withdrawal symptoms in morphine-dependent mice.5-HT2C R may be a novel target to develop therapeutic ap-proach against morphine physical dependence,craving and relapsing.