AIM To study the protective effect of TFA against cerebral ischemia reperfusion injury. METHORDS The cerebral ischemia model in mice was made by means of ligating bilalateral common carotid arteries.The mice survive rate during 6 h was observed,and malondialdehyde (MDA) in the ischemic cerebral cortex was measured. Using nitrogen anoxia model in mice,the survive time was observed. Ligating bilateral common carotid arteries and descending blood pressure,the cerebral ischemia reperfusion model in rabbits was established. The brain of rabbits was initiated by ischemia for 60 min followed by 30 min of reperfusion. The electroencephalogra phy (EEG) of cerebral ischemia and reperfusion was recorded. Malondialdehyde(MDA) and lactate dehydrogenase(LDH) in the ischemic cerebral cortex were measured. RESULTS TFA(30,60,120 mg?kg -1 ) prolonged the survive time after anoxia in mice,enchanced the survive rate after cerebral ischemia and inhibited the increasing of MDA contents in the cerebral cortex in mice.TFA(12,24,48 mg?kg -1 ) inhibitid the changes of EEG,MDA and LDH induced by cerebral ischemia reperfusion in rabbits. CONCLUSION TFA has protective effects on cerebral ischemia reperfusion injury,the mechanism may relate to attenuating free radical and lipid peroxidation.

Aim To study the action mechanism of hyperin(Hyp) on neonatal rat's neuron with anoxia/reoxygenation(A/R).Methods The dissociated neonatal rat brain cells were subjected to 30 min of anoxia or followed 40 min of reoxygenation.Lactate dehydrogenase(LDH),malondialdehyde(MDA)and nitric oxide(NO)in the supernatant were measured.The intracellular free calcium concentration([Ca~(2+)]_i)in brain cells was assayed with Fura 2-AM method.Results Anoxia induced a significant increase of LDH in the supernatant from (62.0±13.0) U·L~(-1)(Sham group)to (116.0±16.6) U·L~(-1)(Control group,P<0.01),and reoxygenation markedly increased LDH and MDA in the supernatant from (45.6±9.2) U·L~(-1) and (9.1±0.9) μmol·L~(-1)(Sham group)to (106.0±17.4) U·L~(-1) and (16.4±2.7) μmol·L~(-1)(Control group,P<0.01),respectively.In the range of 1.0 ～ 16.0 μmol·L~(-1),Hyp markedly and concentration-dependently inhibited anoxia-or reoxygenation-evoked increases of LDH and MDA.1.0～16.0 μmol·L~(-1) Hyp not only inhibited anoxia-induced increase of NO in the supernatant and rise of [Ca~(2+)]_i in brain cells(P<0.05 or P<0.01),but also attenuated reoxygenation-evoked increases of NO and[Ca~(2+)]_i(P<0.05 or P<0.01),Hyp 16.0 μmol·L~(-1) significantly reduced NO and[Ca~(2+)]_i from (34.4±6.3) μmol·L~(-1) and (640±94) nmol·L~(-1) to (25.0±5.1) μmol·L~(-1) and (331±56) nmol·L~(-1),respectively.Conclusion The protective effect of Hyp on A/R-injured neurons may be related to the inhibition of overload of[Ca~(2+)]_i,NO release and lipid peroxidation.

Objective To study the effect of remifentanil precondition on myocardium against ischemia/ reperfusion (I/R) injury. Methods Fifty male SD rats weighing 300-350 g were anesthetized with intraperitoneal 5% pentobarbital 40 mg?kg-1, tracheostomized and mechanically ventilated. Right carotid artery and jugular vein were cannulated for BP monitoring and drug administration. ECG, BP and HR were monitored continuously. The chest was opened and heart exposed via a left thoracotomy. A 6-0 prolene suture was placed around the left coronary artery and a snare was made. The coronary artery was occluded by tightening the snare. Myocardial ischemia was confirmed by the appearance of a regional cyanosis of myocardium, decrease in BP and ST-T changes on ECG. After the surgical procedure a 15-minute stabilization period was allowed. The animals were then randomly divided into 3 groups: Ⅰ control group (CON, n = 9) ; Ⅱ ischemic preconditioning group (IPC, n = 9) and Ⅲ remifentanil preconditioning group which was further divided into 5 subgroups according to the dose of remifentanil (RPC) . In control group the hearts were subjected to 30 min ischemia followed by 120 min reperfusion (I/R). In IPC group the hearts were subjected to 3 episodes of 5 min ischemia in succession at 5 min interval for reperfusion before I/R. In RPC group the animals received 3 periods of 5 min remifentanil infusion at 0.2 (RPC1 , n = 5), 0.6 (RPC2,n = 6), 2 (RPC3 ,n = 8), 6 (RPC4 ,n = 7) or 20 (RPC5 ,n = 6) ?g?kg-1?min-1 at 5 min interval before I/R. MAP, HR and RPP (SP?HR) were recorded before and after I/R. Infarct size (IS) and the area at risk (AAR) were determined by triphenyltetrazolium staining. Results MAP was significantly lower at the end of 30 min ischemia in RPC2, RPC3, RPC4 and RPC5 subgroups than in control group. There was no significant difference in MAP, HR and RPP at the end of 120 min reperfusion among the 3 groups. The infarct size was significantly smaller in IPC and RPC groups than in control group. RPC at 6 ?g?kg-1?min-1 provided best protective effect. The sigmoidal equation of the dose-effect curve was Y = 15.18 + 17.76/ [1 + 10(-2.57-X)]. ED50, was 2.689 ?g?kg-1?min-1.Conclusion Remifentanil and IPC have similar protective effect on the heart against I/R injury.

Aim To study the protective effects of Presumptive endotheliumartmendependent hyperpolarizing factor(EDHF)released from the rat middle cerebral arteries(MCA),which was mediated by acetylcholine(ACh),on primarily cultured hippocampal neurons subjected to hypoxia-reoxygenation injury.Methods Primarily cultured hippocampal neurons was insulted by hypoxia-reoxygenation;EDHF was produced in rat MCA ring by 1 ?mol?L-1 ACh in the presence of NG-nitro-L-argininemethyl ester(L-NAME,a NOS inhibitor)and indomethcacin(Indo,a COX inhibitor);MTT absorbance and the LDH activity were served as the cell injury index,The level of free calcium fluorescence intensity in the cultured hippocampal neurons was monitored by laser scanning confocal microsope.Results Compared with nomal group,MTT absorbance were decreased significantly,LDH activity in the supernate culture fluid and the Ca2+ in hippocampal neurons increased significantly in model group.The conjoined use of 1 ?mol?L-1 ACh and the endothelium-intacted MCA(MCA/Endo)or ACh+MCA/Endo+L-NAME+Indo can repress both the decrease of MTT absorbance and the increases of LDH activity in the supernate culture fluid and the Ca2+ in neurons which resulted from hypoxia-reoxygenation injury;Neither 1 ?mol?L-1ACh alone nor MCA/Endo alone has the similar effects mentioned above,the conjoined use of 1 ?mol?L-1 ACh and the endothelium-denuded MCA(ACh+MCA/-Endo)also has little effect.K+ which concentration is between 25~35 ?mol?L-1 can significantly attenuate the effects afforded by the conjoined use of 1 ?mol?L-1 ACh,MCA/Endo,L-NAME and Indo,but it is not the same situation when it comes to Ba2+.Conclusions Presumptive EDHF can protect primarily cultured rat hippocamal neurons insulted by hypoxia-reoxygenation and the mechanism is partially concerned with the inhibition of calcium overload.

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 study the inhibitory effect of nimodipine on apoptosis induced by cerebral ischemia. METHODS Incomplete cerebral ischemia was made by ligating bilateral common carotid arteries(CCA) in rats. The apoptosis was determined by terminal deoxy-nucleotidyl transforase-mediated dUTP-digoxigenin nick end-labeling(Tunel) method. The DNA fragmentation analysis was measured with the diphenylamine reagent method. RESULTS Ligting of bilateral CCA markedly produced apoptotic cell in cerebral cortex. Nim 2 mg?kg -1 significantly decreased the numbers of apoptotic cells in cortex; Nim 1 mg?kg -1 , 2 mg?kg -1 also inhibited the increase of DNA fragmentation induced by cerebral ischemia. CONCLUSION Nim has inhibitory effect on ischemia-induced apoptosis of cerebral cortex.

Aim To investigate the protective effect of the potent UT receptor(urotensin Ⅱ receptor,UTS2R)antagonist-urantide against myocardial ischemia-reperfusion(I/R)injury and its probable mechanisms in rats.Methods Rat myocardial I/R injury was induced by ligating and untying the left anterior descending coronary artery.The rats were randomly assigned into 6 groups:sham group,model group,urantide 3 ?g?kg-1 group,urantide 10 ?g?kg-1 group,urantide 30 ?g?kg-1 group and Ver(Verapamil)1.6 mg?kg-1 group.All animals except sham group were subjected to 30 min of occlusion and 60 min of reperfusion.Urantide or Ver was given ten minutes before occlusion through intravenous drug perfusion.Heart rate(HR)and the ST segment change of electrocardiogram(ECG)were recorded.The content of malondialdehyde(MDA)and nitric oxide(NO),and the activity of lactate dehydrogenase(LDH)and nitric oxide synthase(NOS)in blood serum were measured.Infarct size(IS),as a percentage of the area at risk(AAR),was determined by Evans blue and TTC double staining.The expression of iNOS protein was detected by western blotting.Results The results demonstrated that during the process of I/R,HR decreased significantly whereas ST segment of ECG markedly elevated.After I/R,MDA content and LDH activity in blood serum increased significantly,while total NO content and total NOS activity decreased sharply.Urantide(10,30 ?g?kg-1)had no significant effect on HR changes,but could markedly inhibit the elevation of ST segment of ECG,MDA content and LDH activity,and inhibit the decline of total NO content and total NOS activity,at the same time decrease I/R induced IS/AAR.But 3 ?g?kg-1 urantide had no significant effect on above indexes.Except for this,urantide(10,30 ?g?kg-1)down-regulated the I/R induced expression of iNOS.Conclusions Our findings indicate that urantide has a protective effect against myocardial I/R injury in rats.The cardio-protective involves the inhibition of lipid peroxidation and the stimulation of NO release.

Urotensin II (U-II), a cyclic peptide has been initially identified as a neuropeptide of teleost fish. Subsequently, U-II has been characterized in the brain of the European green frog and has also been cloned from the human genome. Human U-II (human U-II, hU-II), composed of 11 amino acid residues is rich in cardiovascular and nervous system. As an endogenous ligand for UT receptor, hU-II exerts a broad spectrum of biological actions, such as vasoconstriction and vasorelaxation, facilitating proliferation of cardiac cells, regulating the cardiac function and playing an important role in pathogenesis of some cardiovascular diseases such as coronary heart disease and cardiac failure. The effects of hU-II on cardiovascular system were briefly reviewed as follows.

Aim To study the protective effect of total flavones of rhododendra pharmacological preconditioning(TFR-PP)on myocardial ischemia and reperfusion injury and its mechanisms involved in myocardial inflammation in rats.Methods In model group the isolated perfused rat hearts set up by Langendorff system were subjected to 30 min ischemia followed by 40 min reperfusion. The hearts in TFR-PP groups were subjected to three cycles of 5 min perfusion with and without TFR before 30 min ischemia followed by 40 min reperfusion. In all groups the activities of lactate dehydrogenase (LDH), creatine phosphokinase (CK), and myeloperoxidase (MPO) in myocardium, the expressions of nuclear factor-kappa B (NF-?B), tumor necrosis factor-alpha(TNF-?), and intercellular adhersion molecule-1 (ICAM-1) were measured, and the myocardial pathomorphological changes were examined.Results TFR-PP(25、50、100 mg?L-1) could inhibit markedly the reductions of LDH and SOD activities in myocardium induced by ischemia and reperfusion injury.100 mg?L-1 TFR-PP also significantly improved the pathomorphological changes of injury. TFR-PP (25、50、100 mg?L-1) could inhibit the expressions of NF-?B, TNF-? and ICAM-1 to varying degrees.Conclusion TFR-PP has marked protective effect on ischemia and reperfusion injury in isolated rat heart via inhibiting the inflammation of myocardium.

OBJECTIVE To investigate the protective effect of urantide on myocardial apoptosis in rats induced by ischemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R) injury and explore the underlying mechanism. METHODS ① In vivo test A rat myocardial I/R injury model was induced by ligating and untying the left anterior descending coronary artery with occlusion 30 min/reperfusion 60 min. Urantide 3, 10 and 30 μg·kg-1 was iv given 10 min before ischemia. TUNEL labeling was used for apoptosis measurement in myocardium. Immu-nohistochemical assay was used for Bcl-2 and Bax proteins expression detection. ② In vitro test An H/R cell model was set up by 3 h hypoxia/3 h reoxygenation. Urantide 0.1,1 and 10 nmol·L-1 was added just before hy-poxia, respectively. Hoechst33258 assay and flow cytometric techniques were used to detect apoptotic cells. RESULTS ① In vivo test Compared with sham group, the number of TUNEL-positive cells in I/R model group significantly increased (P<0.01) ; Bcl-2 protein expression slightly increased with no significant difference, Bax protein expression markedly increased ( P < 0. 01 ) , while Bcl-2/Bax ratio in I/R model group significantly decreased (P <0.01). Compared with I/R model group, the number of TUNEL-positive cells in urantide 10 and 30 μg·kg-1 groups was significantly decreased by about 36.6% and 57. 2% (P<0.05) ; Bax protein expression markedly decreased ( P <0.05 ) , while Bcl-2/Bax ratio was significantly augmented ( P <0.05 ). Urantide 30 u,g-kg1 also markedly increased Bcl-2 protein expression(P <0.05). ② In vitro test Compared with normal control group, the apoptosis rate in H/R model group significantly increased (P<0. 01). Hoechst33258 assay revealed that urantide 0.1, 1 and 10 nmol·L-1 reduced H/R-induced apoptotic nuclei by about 27.9% , 59.0% and 75. 4% , respectively (P <0.05). Flow cytometric techniques showed that the apoptosis rate was significantly reduced by about 32.8% and 64. 7% with administration of urantide 1 and 10 nmol·L-1 (P < 0. 01). CONCLUSION Urantide exerts an inhibitory effect on I/R or H/R-induced apoptosis by increasing Bcl-2 protein expression and decreasing Bax protein expression.