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Objective To investigate the protective effect of menatetrenone (MK4) on the osteoblasts in oxidative stress, and to clarify the anti-osteoporosis mechanism of MK4. Methods Mouse osteoblasts (MC3T3-E1) induced by hydrogen peroxide (H2O2) was used. Cell viability, ALP activity and the area of bone nodule were observed. The level of ROS was detected by DCFH-DA, mitochondrial membrane potential by JC-1, apoptosis rate by annexin V-FITC/PI, and the expression of FoxO1, FoxO3, SOD, bcl-2 and bax by RT-PCR. Results Menatetrenone at 10 μmol/L significantly increased the proliferation of osteoblasts stimulated by H2O2, ALP activity, bone nodule formation area, cell membrane potential, the antioxidant SOD and transcription factors FoxO1 and FoxO3 mRNA expression. In the meantime, the elevated malondialdehyde and reactive oxygen species level in cells induced by H2O2, the apoptosis rate and the mRNA expression level of bax/Bcl-2 were significantly reduced. Conclusion menatetrenone can protect osteoblasts from oxidative damage by regulating FoxO pathway and reduce osteoblasts apoptosis by up regulating the proportion of Bcl-2/bax.
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Objective To compare the effects of vitamin K1 (VK1), vitamin K2 (MK4), vitamin K2 (MK7) and vitamin K3 (VK3) on bone formation and bone absorption. Methods Osteoblasts were isolated from calvaria of newborn rats and osteoclasts were induced by receptor activator of nuclear factor-κ B ligand (RANKL). ALP and TRAP activity were measured by diphenyl phosphate method. Osteoclast metabolic activity was measured by Celltiter kit. The inhibition of cathepsin K (CTSK) was measured by Z-FR-MCA fluorescent substrate and collagen substrate degradation. Results MK4 and MK7 at 0.1~1 μmol/L significantly increased the proliferation of osteoblasts (P<0.05) and at 1 μmol/L increased ALP activity and bone nodule formation area. VK3 inhibited bone nodule formation (P<0.05). VK1,VK3,MK4 and MK7 at 1 μmol/L had no effect on osteoclastic bone absorption. MK4 and MK7 significantly inhibited TRAP activity at 0.1~1 μmol/L (P<0.05), while VK1 and VK3 did not show the inhibitory effect. The inhibition of MK4 at 25 μmol/L on CTSK binding to Z-FR-MCA substrate activity is 58.9% and the inhibition of MK4 at 100 μmol/L on collagen degradation of CTSK activity is 73.2%. Conclusion Compared with VK1 and VK3, MK7 and MK4 significantly increase osteoblast activity and inhibit osteoclast bone absorption, MK4 inhibits osteoclast CTSK enzyme activity.
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Objective:To determine the protective effect of cardio-pulmonary bypass(CPB) with autologous lung as oxygenator on CPB-relative inflammatory response.Methods:Twelve adult mongrel dogs were randomly divided into control group and study group.Cardiopulmonary bypass (CPB) using a membrane oxygenator (control group) or using the autologous lung (study group) for gas exchange was performed for 120 min in an alternating series of 12 mongrel dogs with the heart arrested for 90 min by crystalloid cardioplegia and 30 min reperfusion.The blood samples were collected at the same time point of pre-operation(T1),60 min of cardiopulmonary bypass(T2),and 1 hour(T3),2 hours(T4) after cardiopulmonary bypass. Plasma concentration of IL-6,IL-10,TNF-α were detected with ELISA.Results:The plasma levels of IL-6,IL-8,IL-10,TNF-α in each group were significantly increased at T2,T3,T4.The plasma levels of IL-6,IL-8 and TNF-α in study group were significantly lower than in the control group at T2,T3,T4.The plasma levels of IL-10 in study group were significantly higher than the levels in control group at T2,T3,T4.Conclusion:This study indicates that extracorporeal circulation with autologous lung as oxygenator could reduce the increased amplitude of plasma levels of TNF-α,IL-6 and IL-8 whereas enhance the increased amplitude of the plasma IL-10 levels that result from CPB.In other word,extracorporeal circulation with autologous lung as oxygenator possesses the effect to regulate inflammatory cytokine balance and down-regulate CPB-relative inflammatory response.
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Objective To study the effects of ShaJi on the indexes of oxygen metabolism such as coronary blood flow in myocardium of anesthetized thoraco-opened dogs. Methods Dogs were randomly divided into control group,4 and 16 mg?kg-1 ShaJi groups,and positive control group(n=6).The anesthetized thoraco-opened dog models were set up.The administration of intravenous injection was used by femoral vein.The blood pressure,heart rate and coronary blood flow(CBF) were measured.Coronary resistance,myocardial oxygen uptake rate,myocardial oxygen consumption index and myocardial oxygen consumption were calculated.Results Compared with control group,the CBF was increased (P0.05).Conclusion ShaJi can significantly ameliorate oxygen metabolism in myocardium of anesthetized thoraco-opened dogs.
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Objective:The experiment researched relation between applying p38MAPK inhibitor(SB203580) and pulmonary injury during CPB.Methods:18 pigs randomly distributed three groups(n=6). We perfused the lung of the second group with SB203580 during CPB. The first group(n=6) and the second group(n=6) are control group. Lung samples were collected. Activated forms of P38 were measured by Western blot. Pulmonary injury was determined by histology. Tissue water percentage was measured. Pulmonary function was measured.Results:Phospho-P38 of the first group were increased compared with both the second group and the third group(P