Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clo...Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clopidegrol on the development of atherosclerosis, accumulation of lipid- filled macropha-ges in apoE null mice. Methods All mice were done cuffed common carotid artery and fed a Western-type atherogenic diet for 6 weeks from the day of surgery, at same time the therapy group mice were gavaged S18886 5 mg/Kg/day and clopidegrol respec- tively, the same volume water were gavaged as the placebo group. Results profound inhibition of lesion area growth after cuff of the right common carotid artery in mice with 5 mg/kg of S18886, markdely reduce intima to media ratio and intima to total wall area compare with clopidegrol or blank group; Macrophage infiltration into sites of arterial plaque was also markedly attenuated by ICAM-1 deficiency in the S18886 group, whereas inside the arterial wall plaque of placebo apoE null mice α-smooth muscle actin markedly attenuated. Treatment with 25 mg/kg/day clopidegrol reduced the level of ICAM-1 stai ning, both S18886 and clopidegrol didn't influence the α-smooth muscle actin inside plaque. Conclusions It was considered that the novel anti-thrombotic drug significant reduce macrophage infiltration in the sites of arterial plaque by ICAM-1 deficiency, S18886 not only reduce the size, but also stabilized the plaque.展开更多
The effect of high frequency oscillatory ventilation（HFOV） at early stage on hemodynamic parameters, extravascular lung water（EVLW）, lung capillary permeability, CC16 and s ICAM-1 in piglets with pulmonary or extr...The effect of high frequency oscillatory ventilation（HFOV） at early stage on hemodynamic parameters, extravascular lung water（EVLW）, lung capillary permeability, CC16 and s ICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome（ARDS） was explored. Central vein pressure（CVP） and pulse indicator continuous cardiac output（Pi CCO） were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS（ARDSp） and extrapulmonary ARDS（ARDSexp） models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index（EVLWI）, EVLW/intratroracic blood volume（ITBV） and pulmonary vascular permeability index（PVPI） were measured before and after modeling（T0 and T1）, and T2（1 h）, T3（2 h）, T4（3 h） and T5（4 h） after HFOV. CC16 and s ICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group（P〈0.05）. The EVLWI in ARDSp group was increased at T1（P=0.008）, and sustained continuously within 2 h（P=0.679, P=0.216）, but decreased at T4（P=0.007） and T5（P=0.037）. The EVLWI in ARDSexp group was also increased at T1（P=0.003）, but significantly decreased at T3（P=0.002） and T4（P=0.019）. PVPI was increased after modeling in both two groups（P=0.004, P=0.012）, but there was no significant change within 4 h（T5） under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI（P=0.13）, ΔPVPI（P=0.28） and ΔEVLW/ITBV between the two groups（P=0.63）. The significant decreases in both CC16 and s ICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.展开更多
文摘Objectives To investigate whether thromboxane receptor antagonist S18886 inhibits infiltrating macrophages to vessel wall and influence the morphology of atherosclerotic plaque; The effective of S18886 compared to clopidegrol on the development of atherosclerosis, accumulation of lipid- filled macropha-ges in apoE null mice. Methods All mice were done cuffed common carotid artery and fed a Western-type atherogenic diet for 6 weeks from the day of surgery, at same time the therapy group mice were gavaged S18886 5 mg/Kg/day and clopidegrol respec- tively, the same volume water were gavaged as the placebo group. Results profound inhibition of lesion area growth after cuff of the right common carotid artery in mice with 5 mg/kg of S18886, markdely reduce intima to media ratio and intima to total wall area compare with clopidegrol or blank group; Macrophage infiltration into sites of arterial plaque was also markedly attenuated by ICAM-1 deficiency in the S18886 group, whereas inside the arterial wall plaque of placebo apoE null mice α-smooth muscle actin markedly attenuated. Treatment with 25 mg/kg/day clopidegrol reduced the level of ICAM-1 stai ning, both S18886 and clopidegrol didn't influence the α-smooth muscle actin inside plaque. Conclusions It was considered that the novel anti-thrombotic drug significant reduce macrophage infiltration in the sites of arterial plaque by ICAM-1 deficiency, S18886 not only reduce the size, but also stabilized the plaque.
文摘The effect of high frequency oscillatory ventilation（HFOV） at early stage on hemodynamic parameters, extravascular lung water（EVLW）, lung capillary permeability, CC16 and s ICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome（ARDS） was explored. Central vein pressure（CVP） and pulse indicator continuous cardiac output（Pi CCO） were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS（ARDSp） and extrapulmonary ARDS（ARDSexp） models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index（EVLWI）, EVLW/intratroracic blood volume（ITBV） and pulmonary vascular permeability index（PVPI） were measured before and after modeling（T0 and T1）, and T2（1 h）, T3（2 h）, T4（3 h） and T5（4 h） after HFOV. CC16 and s ICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group（P〈0.05）. The EVLWI in ARDSp group was increased at T1（P=0.008）, and sustained continuously within 2 h（P=0.679, P=0.216）, but decreased at T4（P=0.007） and T5（P=0.037）. The EVLWI in ARDSexp group was also increased at T1（P=0.003）, but significantly decreased at T3（P=0.002） and T4（P=0.019）. PVPI was increased after modeling in both two groups（P=0.004, P=0.012）, but there was no significant change within 4 h（T5） under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI（P=0.13）, ΔPVPI（P=0.28） and ΔEVLW/ITBV between the two groups（P=0.63）. The significant decreases in both CC16 and s ICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.
