RESUMO
Aim To explore the mechanism of E.coli heat-labile enterotoxin B subunit(LTB)as adjuvant by analysis of cellular proteins interacting with LTB. Methods Whole cell proteins were purified from RAW 264.7 cell after treated with LTB or NaCl 12 h, respectively.The cellular proteins were interacted with LTB and the interacting proteins were purified by pull-down assay and identified by mass spectrography.The LTB interaction proteins were conformed with Western blot and immunofluorescence assay.Results 25 LTB interaction proteins were found,and their interaction network was mapped;four proteins (Jup,Dsp,Ddx5 and Vimentin)were indicated to be related with LTB adjuvant activity;immunofluorescence assay indicated that GM130 interacted with LTB,however,Vimentin had no interaction with LTB in vivo.After treated by LTB,the expression of β-actin was upregulated obvi-ously in RAW 264.7 cell,whereras,Hspd1 did not show any change.Conclusions LTB exerts adjuvant activity through binding to GM1 of immune cells,cau-sing endocytosis and transporting to the Golgi apparatus by vesicles.Then LTB might bind to Jup and affect TCF/LEF activity,regulating the expression of Bcl 2, IL-6,and Runx3.The result is promoted T cell and B cell proliferation,differentiation and activation by se-cretion of cytokines and immunoglobulins.
RESUMO
A series of andrographolide derivatives with the structure of 12-N-substituted-14-deoxyandrographolide were synthesized from the parent compound andrographolide.Their antitumor activities were preliminarily evaluated on various cancer cell lines and compound 4d stood out due to its potent growth inhibitory effect in comparison with andrographolide.Compound 4d also demonstrated significant antitumor effect on human hepatoma HepG2cells in vitro and on sarcoma 180 (S180) and hepatoma 22(H22)-bearing mice in vivo.Then,the apoptosis induced by compound 4d in HepG2cells was detected by Annexin V/PI double staining assay.Further mechanic study showed that the expression of p53 and Bax was significantly elevated and that of Bcl-2was downregulated in 4d-treated HepG2cells.Collectively,these data suggested that compound 4d had remarkable antitumor effect both in vitro and in vivo and could effectively induce apoptosis via a p53-dependent pathway in HepG2 cells,thus deserving further investigation.
RESUMO
Aim: To investigate the analgesic effect of the new triazole compounds Ⅱ_3 and effects on cycloxygen-ase-1(COX-1) as well as cycloxygenase-2( COX-2). Methods: The hot plate and the stretching settings in mice were utilized to study the effects of compounds Ⅱ_3 on acute pain. Radioimmunologic kits were used to assay the contents of PGE_2 in macrophage and 6-keto-PGF_(1α) in endodermis, which represents the activities of COX-2 and COX-1, respectively. Results: CompoundsⅡ_3( 15,30,60 mg/kg) prolonged the pain liminal value and the writ-hing response time in the initial appearance, and reduced the frequency of the writhing response in 15 min after exposure of the mice to glacial acetic acid( P < 0. 05, P < 0. 01). CompoundsⅡ_3, at the concentrations of 1×10 ~(-5),1×10 ~(-6), and 1×10 ~(-7) mol/L, markedly inhibited the production of PGE_2 in macrophage, and also impeded the activity of COX-2 at 1×10 ~(-6) mol/L But the inhibition of 6-keto-PGFla in endodermis using the same settings of compounds Ⅱ_3 was found to be limited. Conclusion: CompoundsⅡ_3 has analgesic effects on the acute pain and selective inhibition on COX-2.
RESUMO
Objective:To investigate the effect of nimodipine liposomes for injection(NOLI)on focal cerebral ischemia/reperfusion(I/R)injury in rats.Methods:Seventy SD rats were divided into NDLI 1.00 mg/kg,NDLI 0.50 mg/kg,NDLI 0.25 mg/kg,nimodipine 1.00mg/kg,solvent 10 mL/kg,sham-operation and ischemic model groups.The model of middle cerelral artery occlusion in rat was replicated.The behavioral scores in rats were assessed in all groups.The infarct volume,brain water content,biochemical indices of brain homogenate and histology were detected.Results:1he NDLI 1.00mg/kg,0.50 mg/kg and 0.25 mg/kg groups could significantly improve the behavior scores in focal cerebral ischemic rats,reduce the volume of cerebral infarction,decrease the brain water content,improve the activities of Na+,K+-ATPase,Ca2+-ATPase,glutathione(GSH)and superoxide dismutazse(SOD)in brain tissues,reduce conteras of malondialdehyde(MDA),lactic acid(LA)and nitric oxide(NO),and improve histo logical injury.Conclusions:NDLI has the protective effect on focal cerebral ischemia/reperfusion injury in rats.
RESUMO
Aim: To evaluate the effects of HZ08, a novel P-glycoprotein inhibitor, on reversing tumor resistance of K562/ADM to adriamycin in nude mice and on the activities of cytochromes P-450 (GYP) isoforms. Methods: Nude mice bearing K562/ADM were injected at different doses of HZ08 with adriamycin for 4 weeks. The tumor weights of HZ08 treatment groups were determined and compared to those of the control and positive groups. In addition, the effects of HZ08 were examined on GYP isoforms-mediated metabolism of specific substrates by GYP isoforms in rat liver microsomes in the presence or absence of HZ08. Results: The tumor weights of HZ08 treatment groups were significantly decreased and HZ08 was a relatively potent inhibitor of CYP3A4, with no significant effects on other isoforms tested. Conclusion: HZ08 has potent effects on reversing P-glycoprotein mediated tumor multidrug resistance in rive with little influence on cytoehrome P-450 activities of rat liver.
RESUMO
AIM: To study the protective effects of nimodipine liposomes for injection (NDLI) on injuries of total cerebral ischemia/reperfusion(I/R) in rats and anoxia in mice. METHODS: Acute anoxia in mice was produced by hypoxia under normal pressure and decapitation. In these two models the survival time and persistent time of gasping were observed. Ameliorated pulsinelli four-vessel occlusion method was used to make global brain ischemia model. The EEG, the time of righting reflex recovery and Evans blue content in the homogenate of the brain tissues were recorded. RESULTS: NDLI obviously prolonged the survival time and persistent time of gasping in mice subjected to acute anoxia, remarkably shortened the time of EEG recovery and righting reflex recovery, and reduced Evens blue content in the homogenate. CONCLUSION: NDLI has significantly protective effects on injuries of total cerebral I/R and anoxia.
RESUMO
Aim To investigate the protective effects of on focal cerebral ischemic-reperfusion(I/R)injury in rats.Methods The model of rat middle cerebral artery occlusion(MCAO)was induced to observe the change of praxiology of rats,infarction percentage,water content,histology of the rat brains.The levels of superoxide dismutase(SOD),malondialdehyde(MDA),reduced glutathione hormone(GSH),Na+,K+-ATPase,Ca2+-ATPase,nitric oxide(NO)were also measured.Results Salidroside at different dosages(24,12,6 mg?kg-1)could obviously decrease cerebral function score,cerebral infarct size and water content,and repair pathological injury of focal cerebral I/R in rats.MDA,LD,NO contents in brain tissue were significantly decreased and activities of GSH,SOD were significantly improved.Na+,K+-ATPase,Ca2+-ATPase at dosages of 24,12 mg?kg-1 were also significantly improved.Conclusion Salidroside had protective effects on injuries of cerebral I/R.
RESUMO
Endothelial dysfunction plays a crucial role in the development of arteriosclerosis (AS). Accumulating evidence suggests that endothelial dysfunction is an initiating event in the etiology of arteriosclerosis. This article reviewed the relationship between endothelial dysfunction and atherosclerosis, and the effects of therapeutic drugs especially statins on endothelial dysfunction.
RESUMO
AIM:To study the effect of Exendin-4 on the glucose tolerance and serum glucose level in normal animals. METHODS: The fasting blood glucose concentration was tested at 0,1,2,3,4 h and 2,4 week after the first administration of Exendin-4 (0.1, 0.3, 0.9 g/kg, 4 weeks, qd) in Wistar rats ,taking insulin as positive control. Before intragastric administration 2.5 g/kg glucose, Exendin-4 (0.2, 0.6, 1.8 g/kg) were subcutaneously injected, then the fasting blood glucose concentration was tested at 0.5, 1, 2 h after the glucose loading. After hypodermic administration of Exendin-4 (0.2, 0.6, 1.8 g/kg), half of the mice were subcutaneously administrated 2.5 g/kg glucose 15 min later, and the insulin was tested at the end of the experiment. RESULTS:Exendin-4 could not significantly change the fasting blood glucose concentration at different times. The fasting blood glucose concentration was significantly decreased after glucose loading by administration Exendin-4. Exendin-4 could increase the serum insulin concentration remarkably after glucose loading and could not change much without glucose loading. CONCLUSION: The results suggest that the blood glucose regulation of Exendin-4 was related to the concentration of glucose.
RESUMO
AIM: To study antiasthmatic effect of citral from aqueous extract of fruit of cubeb litsea tree and its mechanism.METHODS: By inducing asthma with Ach-histamine method in guinea pig,cough with ammonia in mice and the output quantity of phenol red from the trachea in mice,the antiasthmatic was observed,preventing cough and eliminating phlegm effect of citral. By measuring the tension of guinea-pig isolated tracheal rings,the both influence of citral was observed on isolated guinea pig tracheal rings and inhibition's effects of citral on contraction induced by Ach.RESULTS: Citral prolonged apparently the incubation period of asthma due to Ach-histamine solution in guinea pig and the coughing incubation period,reduced coughing frequency induced by ammonia in mice,increased excretion of phenol red from the respiratory tract in mice,inhibited the constrictions induced by Ach,and shifted the dose-effect curves of Ach to the right.CONCLUSION: Citral has functions of expelling phlegm,relieving cough and resisting asthma,satisfactory bronchi spasmolysis.
RESUMO
AIM:To investigate the protective effect of a new type nerves protectant TQ0701-2,as the derivate of edaravone free radical scavenger,on cerebral ischemia reperfusion injury rat.METHODS:120 male SD rats were randomly divided into sham group,model group,edaravone group(3.0 mg/kg)and TQ0701-2 high-dose group(6.0 mg/kg),middle-dose(3.0 mg/kg)and low-dose group(1.5 mg/kg).Animals in the latter five groups were subjected to transient focal ischemia by the middle cerebral artery occlusion(MCAO)for 2 h before reperfusion,while the sham group wasn't ischemic.The rats were injected with edaravone or TQ0701-2 30 min before ischemic and 0 min,2 h after reperfusion in edaravone and TQ0701-2 groups,sham group and model group were treated with normal saline as well.After 24 h of reperfusion,the infarct ratio,neurological and histological deficient and the changes of pathohistology were evaluated.RESULTS:The infarct ratios and neurological deficit scores in the model group were increased(P
RESUMO
Objective To observe the effects of total flavones from Herba Epimedii(TFHE)on the experimental myocardial ischemia and hemorheology of animals.Methods The model of acute myocardial ischemia of rats was established with pituitrin and the model of acute blood stasis was established with high-molecular dextran.The effects of TFHE on the electrocardiogram J-point of acute myocardial ischemia model and the hemorheology of acute blood stasis model were observed.Besides these,the effects of TFHE on coaglutaion time in mice were observed.Results As compared with the model groups,high-,middle-,and low-dosage groups(24,12,and 6 mg/kg)of TFHE could obviously improve the abnormal electrocardiogram J-point of acute myocardial ischemia model,also could effectively prevent the ascending of whole blood viscosity(high-,middle-,and low-shear rate),packed erythrocyte volume,and fibrinogen.High-and low-dosage groups(34 and 17 mg/kg)of TFHE could obviously lengthen the coaglutaion time in mice.Conclusion The results suggest that TFHE possesses protective effects on ischemic myocardium,which may better hemorheology,decrease the whole blood viscosity,prevent blood from coagulating and improve the circulatation of coronary artery.
RESUMO
Objective To observe the effects of ginkgolides on hypoxia tolerance in mice and on myocardial ischemia injury in rats.Methods The mice were given isoprenaline 20 mg/kg(ip) and the survival time of the mice model under the hypoxic condition was recorded. Rat myocardial ischemia was induced by subcutaneous injection of over- dosage isoprenaline(8 mg/kg). Before modeling, rats were pretreated with ginkgolides 10, 20, 40 mg/kg, of ginkgo biloba( EGb) Extract 300 mg/kg, Propranolol 5 mg/kg,or vehicle for four days. The histological changes of myocardiim, serum creatine phosphokinase (CPK) level and lactate dehydrogenase (LDH) activity, myocardial lactate dehydrogenase(LDH) and superoxide dismutase (SOD) content were detected.Results Ginkgolides could prolong the survival time in the mice under a hypoxic condition, lessen the isoprenaline- induced rat myocardial ischemia, inhibit the activities of serum CPK and LDH and the increase of MDA content in ischemic myocardial tissue, enhance superoxide dismutase (SOD) activity. Conclusion Ginkgolides enhance to hypoxia the tolerance in mice and prevent rats from myocardial ischemic injury. The protective mechanism may be related to its inhibition of the activity of platelet activating factor and oxygen free radical.
RESUMO
Aim To investigate effects of Icariin in rats with acute myocardial ischemia induced by isoproterenol(ISO).Methods Icariin(12,6,3 mg?kg-1) was administrated through iv pathway for five days.Myocardial ischemia model of rats was induced by subcutaneous injection(sc) of ISO(30 mg?kg-1 for two days,once a day).The change of Electrocardiogram(ECG) was observed.The levels of lactate dehydrogenase (LDH),superoxide dismutase(SOD), malondialdehyde(MDA) and nitric oxide(NO)in serum were measured.Cardiac indexes(HW/BW and LVW/BW)and cardiac infarction area(IS/V%)were examined.Results Compared with the model group,Icariin(12,6,3 mg?kg-1) could effectively reverse the evident change of T wave and J point induced by isoproterenol,notably decrease the levels of LDH and MDA in the serum, distinctly increase the levels of SOD and NO in the serum(P