灵芝药用研究进展.PDF
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减轻老年组(≥ 60岁)缺血反应,而缺血180 s或服用一种 K ATP激
动剂nicorandil能明显减轻老年组缺血反应,但nicorandil的效应能
被格列本脲抑制。以上说明老年人 K ATP活性减弱致缺血预处理
保护作用丧失。Ovunc等〔 17〕 让有慢性稳定性心绞痛的 8 例 2 型
糖尿病病人先在空腹状态下进行中间有15 min休息间隙的连续
踏步运动,然后口服10 mg格列本脲,30 min后口服200 ml 3010 %
的糖水,015 h后。再进行上述运动。结果显示,格列本脲能使心
肌缺血的阈值下降,表现为S 2 T段下移的时间、发生心绞痛的时
间和 S 2 T段恢复时间缩短,运动的时间亦缩短。
总之 ,大多数研究认为线粒体 KATP是心肌 IPC的重要组
成部分 ,且可能是最后效应器 ,但也有不同的报道。显而易见
糖尿病动物实验结果显示 ,格列本脲能抑制 KATP参与的 IPC。
但在 2 型糖尿病人中 ,结果不一致 ,且未见在长期应用格列本
脲情况下观察 IPC变化的报道。按循证医学的要求 ,应进行
前瞻性的随机化对照临床试验来评价 Sus对心血管的影响。
参考文献
〔 1〕 Murry CE ,Jennings RB ,Reiner KA. Preconditioning with ischemic :
a delay of lethal cell in jurry in ischemic myocardium. Circulation ,1986 ;74 :1124
〔 2〕 Gross GJ , Fryer RM. Sarcolemmal versus mitochondrial ATP 2
sensitive K+
channels and myocardial preconditioning [ J ] . Cire
Res ,1999 ;84 :973
〔 3〕 Toyoday ,Friehs I ,Parker RA ,et al. Differential role of sarcolemmal and
mitochondiral KATP channels in adenosine 2 enchanced ischemic
preconditioning [J ].AmJ Physiol Heart Circ Physiol ,2000 ;279 :2694
〔 4〕 Gaudette GR , Krukenkamp IB ,Saltman AE,et al. Preconditioning with
PKC and the ATP 2 sensitive potassium channels : a codependent
relationship [J ].Ann Thorac Surg ,2000 ;70 :602
〔 5〕 Pain T , Yang XM , Critz SD , et al . Opening mitochondiral KATP
channels t riggers the preconditioned state by generating f ree radicals
[J ] . Cire Res ,2000 ;87 :460
〔 6〕 Macho P ,Solis E ,Sanchez O ,et al . Mitochondiral KATP dependent
potassium channels mediate non 2 ischemio preconditioning by
tachycardia in dogs [J ] . Mol Cell Biochem ,2001 ;216 :129
〔 7〕 Miuro T , Kawamura S , Tatsuno H , et al : Ischemic precondition
attenuates cardiac sympathetic nerve injury via ATP 2 sensitive
potassium channels during myocardial ischemia ,Circulation ,2001 ;
104 :1053
〔 8〕 Alekeev AE , Brady PA , Terzic A. Ligand 2 insensitive state of
cardiac ATP 2 sensitive K+
channels. Basis for channel opening
[J ] . J Gen Physiol ,1998 ;111 :381
〔 9〕 Grovel GJ . Pharmacology of ATP 2 sensitive potassium channel KATP
openers in models of myocardial ischemia and reperfusion [J ] . 1997 ;
75 :309
〔 10〕 冯力,刘伊丽,查道刚,等.经静脉心肌声学造影技术评价 ATP
敏感钾通道的开放对心肌缺血的保护作用. 中国超声医学杂
志,2001 ;17 :81
〔 11〕 Mocanu MM, Maddock HL , Baxter GF , et al. Glimepiride , a novel
sulfonylurea, dose not abolish myocardial protection afforded by either
ischemic preconditioning on diazoxide [J ]. Circulation ,2001 ;103 :3111
〔 12〕 Ghosh S , Standen NB , Galinanes M. Evidence for mitochondiral
KATP channels as effectiors of human myocardial preconditioning
[J ] . Cardiovase Res ,2000 ;45 :934
〔 13〕 Tomai F ,Crea F ,Gaspardone A ,et al. Myocardial preconditioning during
coronary angioplasty is prevented by glibenclamide , a selective ATP 2
sensitive K+
channels blocker [J ]. Circulation ,1994 ;90 :700
〔 14〕 Scognamiglio Roldano ,Avogaro Angelo ,Vigili 2 de 2 Kreutzenberg Saula ,et al. Effects of treatment with sulfonlurea drugs or insulin on ischemia
induced myocardial dysfunctionin type 2diabetes [J ]. Diabetes ,2002 ;51 :
808
〔 15〕 Ghosh S , Standen NB , Galinianges M. Failure to precondition
pathological human myocardium [ J ] . J Am Coll Cardiol , 2001 ;
37 :711
〔 16〕 Lee Tsung 2 Ming ,Su Sheng 2 Fang ,Chou Tsai 2 Fwu ,et al . Loss ......
动剂nicorandil能明显减轻老年组缺血反应,但nicorandil的效应能
被格列本脲抑制。以上说明老年人 K ATP活性减弱致缺血预处理
保护作用丧失。Ovunc等〔 17〕 让有慢性稳定性心绞痛的 8 例 2 型
糖尿病病人先在空腹状态下进行中间有15 min休息间隙的连续
踏步运动,然后口服10 mg格列本脲,30 min后口服200 ml 3010 %
的糖水,015 h后。再进行上述运动。结果显示,格列本脲能使心
肌缺血的阈值下降,表现为S 2 T段下移的时间、发生心绞痛的时
间和 S 2 T段恢复时间缩短,运动的时间亦缩短。
总之 ,大多数研究认为线粒体 KATP是心肌 IPC的重要组
成部分 ,且可能是最后效应器 ,但也有不同的报道。显而易见
糖尿病动物实验结果显示 ,格列本脲能抑制 KATP参与的 IPC。
但在 2 型糖尿病人中 ,结果不一致 ,且未见在长期应用格列本
脲情况下观察 IPC变化的报道。按循证医学的要求 ,应进行
前瞻性的随机化对照临床试验来评价 Sus对心血管的影响。
参考文献
〔 1〕 Murry CE ,Jennings RB ,Reiner KA. Preconditioning with ischemic :
a delay of lethal cell in jurry in ischemic myocardium. Circulation ,1986 ;74 :1124
〔 2〕 Gross GJ , Fryer RM. Sarcolemmal versus mitochondrial ATP 2
sensitive K+
channels and myocardial preconditioning [ J ] . Cire
Res ,1999 ;84 :973
〔 3〕 Toyoday ,Friehs I ,Parker RA ,et al. Differential role of sarcolemmal and
mitochondiral KATP channels in adenosine 2 enchanced ischemic
preconditioning [J ].AmJ Physiol Heart Circ Physiol ,2000 ;279 :2694
〔 4〕 Gaudette GR , Krukenkamp IB ,Saltman AE,et al. Preconditioning with
PKC and the ATP 2 sensitive potassium channels : a codependent
relationship [J ].Ann Thorac Surg ,2000 ;70 :602
〔 5〕 Pain T , Yang XM , Critz SD , et al . Opening mitochondiral KATP
channels t riggers the preconditioned state by generating f ree radicals
[J ] . Cire Res ,2000 ;87 :460
〔 6〕 Macho P ,Solis E ,Sanchez O ,et al . Mitochondiral KATP dependent
potassium channels mediate non 2 ischemio preconditioning by
tachycardia in dogs [J ] . Mol Cell Biochem ,2001 ;216 :129
〔 7〕 Miuro T , Kawamura S , Tatsuno H , et al : Ischemic precondition
attenuates cardiac sympathetic nerve injury via ATP 2 sensitive
potassium channels during myocardial ischemia ,Circulation ,2001 ;
104 :1053
〔 8〕 Alekeev AE , Brady PA , Terzic A. Ligand 2 insensitive state of
cardiac ATP 2 sensitive K+
channels. Basis for channel opening
[J ] . J Gen Physiol ,1998 ;111 :381
〔 9〕 Grovel GJ . Pharmacology of ATP 2 sensitive potassium channel KATP
openers in models of myocardial ischemia and reperfusion [J ] . 1997 ;
75 :309
〔 10〕 冯力,刘伊丽,查道刚,等.经静脉心肌声学造影技术评价 ATP
敏感钾通道的开放对心肌缺血的保护作用. 中国超声医学杂
志,2001 ;17 :81
〔 11〕 Mocanu MM, Maddock HL , Baxter GF , et al. Glimepiride , a novel
sulfonylurea, dose not abolish myocardial protection afforded by either
ischemic preconditioning on diazoxide [J ]. Circulation ,2001 ;103 :3111
〔 12〕 Ghosh S , Standen NB , Galinanes M. Evidence for mitochondiral
KATP channels as effectiors of human myocardial preconditioning
[J ] . Cardiovase Res ,2000 ;45 :934
〔 13〕 Tomai F ,Crea F ,Gaspardone A ,et al. Myocardial preconditioning during
coronary angioplasty is prevented by glibenclamide , a selective ATP 2
sensitive K+
channels blocker [J ]. Circulation ,1994 ;90 :700
〔 14〕 Scognamiglio Roldano ,Avogaro Angelo ,Vigili 2 de 2 Kreutzenberg Saula ,et al. Effects of treatment with sulfonlurea drugs or insulin on ischemia
induced myocardial dysfunctionin type 2diabetes [J ]. Diabetes ,2002 ;51 :
808
〔 15〕 Ghosh S , Standen NB , Galinianges M. Failure to precondition
pathological human myocardium [ J ] . J Am Coll Cardiol , 2001 ;
37 :711
〔 16〕 Lee Tsung 2 Ming ,Su Sheng 2 Fang ,Chou Tsai 2 Fwu ,et al . Loss ......
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