目的:探讨丝裂素活化蛋白激酶(P38MAPK,P38)是否参与去甲肾上腺素预处理的延迟保护作用。方法:18只大鼠随机分成三组:(1)缺血／再灌注(I／R)组;(2)NE预处理组;(3)SB203580(P38的特异性抑制剂)+NE预处理组。于预处理后24 h对心脏进行较...目的:探讨丝裂素活化蛋白激酶(P38MAPK,P38)是否参与去甲肾上腺素预处理的延迟保护作用。方法:18只大鼠随机分成三组:(1)缺血／再灌注(I／R)组;(2)NE预处理组;(3)SB203580(P38的特异性抑制剂)+NE预处理组。于预处理后24 h对心脏进行较长时间缺血再灌注,观察其心肌梗塞范围、LDH释放。结果:与未预处理组的心肌组织比较,于NE预处理后24 h I／R所致的心梗范围缩小,血浆LDH活性降低(P均<0.01)。用SB203580抑制P38磷酸化时,则消除了预处理后的延迟保护作用,上述心肌损伤指标接近单纯缺血／再灌注组(P>0.05)。结论:去甲肾上腺素预处理有使心肌减少缺血／再灌注损伤的延迟保护作用,P38参与了这种保护作用。展开更多
Aims: The sympathetic nervous system plays a central role in cardiac growth but its overstimulation is associated with increased mortality in patients with chronic heart failure. Presynaptic α 2- adrenoceptors are es...Aims: The sympathetic nervous system plays a central role in cardiac growth but its overstimulation is associated with increased mortality in patients with chronic heart failure. Presynaptic α 2- adrenoceptors are essential feedback regulators to control the release of norepinephrine from sympathetic nerves. In this study we tested whether a deletion polymorphism in the human α 2C- adrenoceptor gene(α 2CDel322- 325) affects progression of heart failure in patients with dilated cardiomyopathy(DCM). Methods and results: We genotyped and phenotyped 345 patients presenting with DCM in the heart transplant unit of the German Heart Institute, starting in 1994. Patients were treated according to guidelines(99% ACEI, 76% β - blockers)and were followed until December 2002 or until a first event [death, heart transplantation, or implantation of a left ventricular assist device(LVAD) for a life- threatening condition] occurred. Mean follow- up time was 249 weeks(4.9 years) in event- free patients and 104 weeks(2 years) in patients with events. During follow- up, 51% of the patients exhibited an event: death(18% ), implantation of LVAD as bridging for transplantation(7% ), or heart transplantation(25% ). By Kaplan- Meier analysis, DCM patients with the deletion variant Del322- 325 in the α 2C- adrenoceptor showed significantly decreased event rates(P=0.0043). Cox regression analysis revealed that the presence of the deletion was associated with reduced death rate(relative risk: 0.129, 95% CI: 0.18- 0.9441, P=0.044) and event rates(relative risk: 0.167, 95% CI: 0.041- 0.685, P=0.012). Conclusion: α 2C- Adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guidelines.展开更多
文摘目的:探讨丝裂素活化蛋白激酶(P38MAPK,P38)是否参与去甲肾上腺素预处理的延迟保护作用。方法:18只大鼠随机分成三组:(1)缺血／再灌注(I／R)组;(2)NE预处理组;(3)SB203580(P38的特异性抑制剂)+NE预处理组。于预处理后24 h对心脏进行较长时间缺血再灌注,观察其心肌梗塞范围、LDH释放。结果:与未预处理组的心肌组织比较,于NE预处理后24 h I／R所致的心梗范围缩小,血浆LDH活性降低(P均<0.01)。用SB203580抑制P38磷酸化时,则消除了预处理后的延迟保护作用,上述心肌损伤指标接近单纯缺血／再灌注组(P>0.05)。结论:去甲肾上腺素预处理有使心肌减少缺血／再灌注损伤的延迟保护作用,P38参与了这种保护作用。
文摘Aims: The sympathetic nervous system plays a central role in cardiac growth but its overstimulation is associated with increased mortality in patients with chronic heart failure. Presynaptic α 2- adrenoceptors are essential feedback regulators to control the release of norepinephrine from sympathetic nerves. In this study we tested whether a deletion polymorphism in the human α 2C- adrenoceptor gene(α 2CDel322- 325) affects progression of heart failure in patients with dilated cardiomyopathy(DCM). Methods and results: We genotyped and phenotyped 345 patients presenting with DCM in the heart transplant unit of the German Heart Institute, starting in 1994. Patients were treated according to guidelines(99% ACEI, 76% β - blockers)and were followed until December 2002 or until a first event [death, heart transplantation, or implantation of a left ventricular assist device(LVAD) for a life- threatening condition] occurred. Mean follow- up time was 249 weeks(4.9 years) in event- free patients and 104 weeks(2 years) in patients with events. During follow- up, 51% of the patients exhibited an event: death(18% ), implantation of LVAD as bridging for transplantation(7% ), or heart transplantation(25% ). By Kaplan- Meier analysis, DCM patients with the deletion variant Del322- 325 in the α 2C- adrenoceptor showed significantly decreased event rates(P=0.0043). Cox regression analysis revealed that the presence of the deletion was associated with reduced death rate(relative risk: 0.129, 95% CI: 0.18- 0.9441, P=0.044) and event rates(relative risk: 0.167, 95% CI: 0.041- 0.685, P=0.012). Conclusion: α 2C- Adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guidelines.
