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Objective@#To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice.@*Methods@#We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 μg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed.@*Results@#Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro. Doxorubicin induced the G2/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm3, (216.80±57.18)mm3, (246.10±21.90)mm3, (327.50±44.24)mm3, (213.30±32.31)mm3 and (495.80±75.87)mm3 in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo (P<0.001). The median survival times were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above, respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM-CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control (P<0.05).@*Conclusion@#Synergistic effect of sequential treatment with doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.
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Aim To investigate the protective effect of compound total flavonoids on atherosclerosis in ApoE -/- knockout mice.Methods Seven-week old C57BL/6 mice considered of the normal group (n =1 5 );seven-week old ApoE -/- mice were fed with high-fat diet and were assigned randomly into 5 groups:model group,simvastatin group,the low com-pound flavonoids group,the middle compound fla-vonoids group and the high compound flavonoids group.After 1 6 weeks,mice serum and aortas were harvested.The formation of atherosclerotic plaque was analyzed by HE staining,The serum level of lipids pro-files and superoxide dismutase (SOD )were deter-rnined.The levels of IL-1 βand NF-κB in serum were detected by ELISA assay.Results Area of atheroscle-rotic lesion was significantly less in the compound fla-vones group than in model.The level of TC,TG,LDL-C,IL-1 β,NF-κB in serum of the compound flavonoids group were decreased significantly,while SOD and HDL-C increased significantly compared with the mod-el group,and the difference was significant (P <0.05).Conclusion The compound flavonoids have a good protective effect on early atherosclerosis in mice, which may be due to its alleviating effects on hyperlipi-demia and inflammation and oxidation.
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Aim To explore the role of endoplasmic reticulum stress (EPR) in high fatty acid induced injury in cardiomyocytes.Methods Cardiomyocytes were exposed to different concentrations of palmitic acid (0, 0.1, 0.2, 0.4 mmol·L-1) for 24 h and different time points of high palmitic acid (0.2 mmol·L-1) (12, 24, 48 h).Cell viability was measured by CCK8, and the protein expressions of EPR such as GRP78, CHOP, PERKphos, IRE1phos, ATF6 and apoptosis related proteins such as Bcl-2 and Bax were determined by Western blot.Results When the cells were stimulated with palmitic acid (0.1~0.4 mmol·L-1) for 24 h, the cell proliferation rates of 0.2 and 0.4 mmol·L-1 groups were significantly decreased.Cardiomyocytes exposured to high palmitic acid (0.2 mmol·L-1) for 24 h showed an increase in theexpression of EPR related proteins (GRP78, CHOP, PERKphos, IRE1phos and ATF6) and Bax(P<0.05), while Bcl-2 expression was significantly reduced.Pretreatmented with EPR inhibitor pravastatin(10 mol·L-1) significantly increased high palmitic acid induced Bcl-2 expression (P<0.05) and significantly decreased high palmitic acid induced Bax expression (P<0.05).Conclusion Activated EPR might play an important role in treatment of high fatty acid induced myocardial injury.
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AIM To investigate if the protective effect of baicalin on cerebral injury induced by transient focal ischemia is related to modulation of expressions of inflammatory cytokines or adhesive molecules. METHODS Transient focal cerebral ischemia injury model in rats was induced by occlusion of the right middle cerebral artery for 2 h, followed by 24 h reperfusion. The infarct volume and neurological deficit were determined by TTC staining and the scoring method of Longa et al. The expression of intracellular adhesion molecule-1 (ICAM-1), neutrophils infiltration, and myeloperoxidase (MPO) activity in brain were measured by immunohistochemistry, hematoxylin-eosin staining, and spectrophotometer, respectively. Semiquantitative RT-PCR was employed to assess the expression of inducible nitric oxide synthase (iNOS) mRNA. The level of interleukin-1 (IL-1) in brain was assayed by radioimmunoassay. The expression of nuclear factor-κB (NF-κB) protein was evaluated by Western blot. RESULTS After transient cerebral ischemia, MPO activity and the expression of ICAM-1 in the periphery of ischemic cortex were significantly increased. Increase in iNOS mRNA and NF-κB protein expression was also shown in the ischemic area. Treatment with baicalin markedly reduced brain infarct volume and neurological deficit induced by ischemic insult, inhibited MPO activity, inflammatory cell infiltration, as well as expression of ICAM-1, iNOS and NF-κB, and decreased IL-1 level. CONCLUSION Baicalin may play a protective effect on cerebral ischemic injury through inhibiting the expression and release of the inflammatory mediators after cerebral ischemia.
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AIM: To study the protective effects of baicalin on myocardial ischemia-reperfusion injury in rats. METHODS: The models of myocardial ischemia-reperfusion injury were established by occluding left anterior descending coronary artery (LAD) for 30 min, followed by reperfusion for 120 min. The rate of rise and decline of left ventricular pressure (±dp/dtmax) and end-diastolic pressure of left ventricle (LVEDP) were monitored continuously with polygraph. After reperfusion, the blood and myocardium samples were taken for determination of malondialdehyde (MDA) content, superoxide dismutase (SOD), Na+-K+-ATPase, Ca2+-ATPase activities in myocardium, creatine kinase (CK) and lactate dehydrogenase (LDH) in serum with spectrophotometer. The ultrastructural changes in ischemic myocardium were assessed by transmission electron microscope. RESULTS:dtmax and LVEDP, decreased plasma CK and LDH levels, reduced myocardial MDA content, and increased the activities of SOD, Na+-K+-ATPase, and Ca2+-ATPase in myocardium following ischemia-reperfusion. The ultrastructural injury in reperfused myocardium was relieved. CONCLUSION: Baicalin possesses a protective effect against myocardial ischnemia-reperfusion injury through scavenging oxide radicals and improving Na+-K+-ATPase and Ca2+-ATPase activities.
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Aim To explore the effects of lipoteichoic acid (LTA) induced delayed preconditioning (PC) on hypoxia-reoxygenation (H/R) injury of cultured human coronary artery endothelial cells (HCAECs), and to investigate the potential role of endogenous nitric oxide (NO) participated in the protective mechanism. Methods HCAECs were incubated for 2 h in a hypoxic atmosphere and reoxygenated for 4 h in a normoxic atmosphere. The delayed PC was induced by pretreatment with LTA assessed by the percentage of cellular injury with Trypan blue exclusion and by the amount of lactate dehydrogenase (LDH) in culture media. The NO level of the culture media was measured detect the expression of eNOS mRNA by RT-PCR method after cells were recovered from different points.Results LTA pretreatment significantly decreased the percentage of the killed cell and the concentration of LDH in media. Also, LTA pretreatment obviously raised the concentrations of NO in culture media. The protective effects of LTA were abrogated by pretreatment with N-monomethyl-L-arginine (L-NMMA).Moreover, the expression of eNOS mRNA was significantly upregulated after HCAECs exposure to LTA for 4 h following 2 h or 4 h recovery. Conclusion LTA could induce the delayed protection against H/R induced endothelial injury and dysfunction of cultured HCAECs. NO produced by eNOS acts initially as a trigger and subsequently as a mediator of delayed PC.
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Aim To observe the protective effects and its mechanisms of Garlic Polysaccharide(GP) on toxic cardiac myocyte induced by adriamycin (ADR). Methods Primary culture neonatal SD rat cardiac myocyte and ADR injury model were established. The activities of several superior fluid and cells enzymes were measured. Using MTT assay and flow cytometry, the apoptotic cardiac myocyte was shown. Results ADR increased the superior fluid creatine kinase (CK), lactate dehydrogenase(LDH), glutamic oxaloacetic transaminase (GOT), and augmented myocardial malondialdehyde (MDA) content, while decreased the superoxide dismutase (SOD) activities (P
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To explore the potential of lipoteichoic acid (LTA) induced cardioprotection against ischemia-reperfusion (I/R) injury in isolated rat hearts and whether endogenous nitric oxide (NO) participates in the protection, the rats were pretreated with LTA (1 mg/kg, i.p.) 24 h before the experiment, and the isolated hearts were subjected to 30 min no-flow normothermic global ischemia and 60 min reperfusion after a 20-min stabilization period by the langendorff method. Cardiac functions were evaluated at the end of stabilization, and at 30 min, 60 min of reperfusion. The amounts of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase(LDH) and total NO oxidation products in the coronary effluent were measured spectrophotometrically at the end of reperfusion. It was revealed that pretreatment with LTA could significantly improve the recovery of cardiac function, reduce the release of CK-MB and LDH, and increase the concentrations of NO in coronary effluent. The protective effects were abrogated by pretreatment of the rats with L-NAME. It was concluded that LTA could induce the delayed cardioprotection against I/R injury, and endogenous NO may be involved in the mechanisms.
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Animals , Male , Rats , Cardiotonic Agents , Pharmacology , Creatine Kinase , Metabolism , Creatine Kinase, MB Form , In Vitro Techniques , Ischemic Preconditioning, Myocardial , Isoenzymes , Metabolism , L-Lactate Dehydrogenase , Metabolism , Lipopolysaccharides , Pharmacology , Myocardial Reperfusion Injury , Nitric Oxide , Metabolism , Rats, Wistar , Teichoic Acids , PharmacologyABSTRACT
Objective:To study the effect of diammonium glycyrrhizinate (DG) on left ventricular function impairment during myocardial ischemia－reperfusion in rats. Methods:The left ventricular was cannulated through right common carotid artery on the myocardial ischemia－reperfusion injury model. The left ventricler function was assessed before and 10 minutes after the administration of DG, immediate and 20 minutes after initiation of ischemia, immediate and 30, 60 minutes after reperfusion, by measuring the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ＋dp*dtmax and －dp*dtmax. Results:Compared with the baseline, all measurements of LVSP, ＋dp*dtmax and －dp*dtmax decreased (P＜0.05,P＜0.01), while LVEDP increased (P＜0.01) after administration of DG. As the time of ischemia－reperfusion lasting, LVSP, dp*dtmax and －dp*dtmax generally decreased progressively, while LVEDP generally increased progressively. 20 minutes after the initiation of ischemia and immediate, 30 and 60 minutes following reperfusion, LVSP, ＋dp*dtmax and －dp*dtmax in the DG group were significantly higher than those in IR group (P＜0.01), LVEDP significantly lower than that in IR group (P＜0.01) at the same time. Conclusion:DG can protect left ventricular function against myocardial ischemia－reperfusion injury in rats.
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Objective: To study the protective effects of tetrahydropalmatine (THP) against ischemia－reperfusion induced hippocamp lesion in rats. MethodS: A model of ischemia-reperfusion induced brain lesion was set up by ligation of common carotid arteria in rats, and the protective effects of THP was observed. Results: It was found that, with administration of THP, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and Na+, K+-ATPase as well as Ca2＋－ATPase were increased (P＜0.05, respectively), while malondialehyde (MDA) was decreased to 42.5% (P＜0.01) during brain ischemia－reperfusion. Conclusion:The results suggested that THP can protect the rat against ischemia－reperfusion induced brain lesion.
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Objective To observe the effects of diammonium glycyrrhizinate (DG) on arrhythmia induced by acute myocardial ischemia-reperfusion injury.Methods Electrocardiogram of lead Ⅱwas examined on the myocardial ischemia-reperfusion model,which was induced by the 10 min of ligation of left descending coronary artery and then 30 min of reperfusion in rats.Myocardial malondialdehyde (MDA) content,superoxide dismutase (SOD) activity and adenosine triphosphatase (ATPase),and serum lactate dehydrogenase (LDH) and creatine phosphokinase (CK) levels were measured.Results As compared with the model,DG significantly reduced the incidence of ventricular arrhythmia and its score (P
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Aim To investigate the protective effect of rosiglitazone on cerebral ischemia/reperfusion injury inrats. Methods Transient focal cerebral ischemia injury model in rats was induced by occlusion of the right middle cerebral artery for 2 h, followed by 24 h reperfusion. The infarct volume and neurological deficit were determined by the method of TTC staining and the Longa′s score, and used to evaluate the effect of rosiglitazone on cerebral injury. The levels of malondialdehyde (MDA), nitric oxide (NO), activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and nitric oxide synthase (NOS) in brain were measured by spectrophotometer. Immunohistochemistry was employed to assess the expression of intracellular adhesion molucule-1 (ICAM-1). The histopathological change was observed after HE staining. Results Pretreatment with rosiglitazone markedly reduced brain infarct volume and neurological deficit induced by transient ischemia, inhibited MPO activity, as well as expression of ICAM-1; it also decreased NO, MDA levels and NOS activity, increased SOD activity, and improved histopathological injury. Conclusion Rosiglitazone has a protective effect on cerebral ischemia/reperfusion injury through inhibiting inflammatory process and lipid peroxidation.
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Aim To study the inhibitory effects and its mechanis ms of Garlic Polysaccharide (GP) on adriamycin(ADR)-induced cardiotoxicity in mic e.Mehtod ADR was injected intraperitoneally to induce myocardiu m injury model in mice. The activities of several serum and heart tissue enzymes were measured. With scanning electron microscope, the cardiac ultrastructural c hanges were examined.Results ADR (3 mg?kg -1 ip, qod?7) induced severe myocardial damages with the increasing activities of creatine kin ase (CK), lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) a nd inducible nitric oxide synthase (iNOS) (P
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IHC-65 was found to be a potent inhibitor of platelet function . It inhibited platelet aggregation induced by threshold concentration of ADP, arachidonic acid and collagen with dose-dependent manner in vitro, and at 96?mol/L, AIR ( aggregation inhibition rate,) were 71.56, 66.93 and 68.47% respectively. IHC-65 inhibited platelet serotonin release induced by collagen,and at 96 ?mol/L, release inhibition rate was 82.97%. IHC-65 did not influence cAMP level in platelet significantly. It is concluded that IHC-65 inhibited platelet aggregation and its action mechanism may be related to inhibition of serotonin release and to antagonizing Ca ++ .
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AIM: To study the potential effects of lipoteichoic acid (LTA)-induced delayed preconditioning (PC) on cardioplegic arrest/reperfusion injury in donor rat heart. METHODS: The rats were pretreated with LTA (1 mg/kg, ip) 24 h before the experiment, and the isolated hearts were subjected to arrested by cardioplegic solution and stored in Eurocollin's solution for 4 h by the Langendorff method, and to evaluate the changes of cardiac function at the reperfusion for 30 min and 60 min, to measure the amounts of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and total nitric oxide (NO) oxidation products in the coronary effluent, and to detect myocardial apoptosis on tissue samples of left ventricle at the end of reperfusion by TUNEL staining. RESULTS: Pretreated with LTA significantly improved the recovery of cardiac function with a significant increase in coronary flow (CF), left ventricular developed pressure (LVDP), maximal rate of left ventricular developed pressure (+dp/dt_ max), and minimal rate of left ventricular decline pressure (-dp/dt_ max) at 30 min and 60 min of reperfusion (all P
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AIM To investigate the preventive effects of taurine on the left ventricle hypertrophy in renovascular hypertensive rats. METHODS Two-kidney 1-clip (2K1C) rats were used to establish the model of renovascular hypertension. The myocardial local aldosterone(Ald) and AngⅡconcentration (MDC,MAC) were measured by radioimmunoassay. Expression of oncogene c-fos mRNA was analyzed by means of in situ hybridization. The myocardial collagen concentration (MCC) was measured by biochemical method. The myocardial tissue structure was observed under the microscope ,and the myocardial fiber diamension (MFD) was measured with micrometer. The linear correlation between MCC, MFD and MAC or MDC was analysed respectively. RESULTS Compared with sham operated rats ,the MCC, MAC, MDC and MFD were significantly increased in 2K1C rats ( P