全 文 ：Chinese Bulletin of Life Sciences
17 2
2005 4
Vol. 17, No. 2
Apr., 2005
201203
3 -
A T P
R 9 7 1 Q 4 2 7 A
The protective effects on the brain by pharmacological preconditioning
XIAO Liang, ZHU Xing-Zu*
(Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences,
Chinese Academy of Sciences, Graduate School of CAS, Shanghai 201203, China)
Abstract: Based on endogenous protective mechanisms of ischemic preconditioning, pretreatment of some
chemical agents was found to be capable of inducing protective effects in brain tissues in recent years. This
phenomenon was defined as pharmacological preconditioning. The chemical agents include endotoxin and its
analogs, 3-nitropropionic acid, volatile anesthetics, adenosine and its mimetic agents, the openers of ATP-
sensitive potassium channels, morphine and desferroxamine, et al. The time course, potency and mechanisms
of the protective effects vary among the different chemical agents. New drugs that could induce pharmacologi-
cal preconditioning may be useful in protection of the brain in neurosurgery or in prevention of ischemic brain
damages.
Key words: pharmacological preconditioning; brain; protective effects
1004-0374(2005)02-0165-05
2004-06-18 2004-07-09
(30128004); (2004CB720305)
( 1 9 7 4 ) ( 1 9 4 6 ) *
[1]
[1~2]: (1)
(trigger) (sensor) (2)
(transducer)
(3)
(effector)
166
(pharmacological preconditioning)
1
1997 [3]
48 72
4
48 72 4
22.8 25.9 20.5%[3]
[4]
[4]
15
4 24
24
(PMNs)
PMNs
[4]
-α
-α
-α
[5] 6
48 TNF-α
TNF-α
[ 5 ]
ω-
-L- (nitro-L-arginine methyl ester L-
NAME) [6]
-
β1 -β1
-β1
-β1
[7]
[8]
A
24
A
[ 9 ]
2 3- (3-nitropropionic acid 3-NPA)
3-NPA
II
3-NPA
3-NPA
3-NPA
[10] 1
3 [10] 3-NPA
1~6 3-NPA
8
[10] 3-NPA
(20 mg/kg) 1 15
45 90%[11] 3-NPA
24
48 3-NPA 3
[12] 3 3 -NPA
(20mg/kg) 70%
ATP 3
3 120
4 16%
23%
3
3-NPA
20
3-NPA
[13]
3-NPA
[10] ATP
5-hydroxydecanoate (5-HD)
3-NPA [14] 3-
NPA ATP
3-NPA
ATP
[14]
24 3-NPA 15 96
3-NPA bcl-2 bax mRNA
3-NPA
15 3 bcl-2
bax
[15] 3-NPA
CA1 c-Jun (c-Jun NH2-terminal kinases
JNK ) N- -D-
(NMDA) [11]
3
3
12~24 3
0 12 24
31% 35% 34%[16] (2.25%)
1 5 24
[17]
24
49
(1%)
30 [18]
- A NMDA
[16]
[16]
ATP
ATP
[17]
[18]
DL-threo-β-hydroxyaspartic acid (THA)
[18]
4
A1 8- -1,3-
(8-cyclopentyl-1,3-dipropylxanthine DPCPX)
(theophylline)
A1
[19~20] (propentofylline)
[21]
R-
(R-phenylisopropyladenosine R-PIA) 15
10 [22]
3 [23] R-PIA
3
[24]
3 70
[24]
ATP [22~23]
5 ATP
(cromakalim
10 mM ) 15 10
[22] 3
[24] (diazoxide) ATP
[25] ATP
ATP [22]
[25]
168
3 70
[24]
C C
(chelerythrine)
[ 2 5 ]
6
24
(pentylenetetrazol)
CD50 ( 50%
) [26]
[27]
κ µ nor-binaltorphimine
(nor-BNI) cyprodime
U-69 593 DAMGO
κ µ [26]
δ
ATP [27]
7 (desferroxamine)
Fe3+
[28]
300 mg/kg 48
72 22
35 100 300 1 000 mg/kg 72
17 35 16
(300 mg/
kg) 72 40
(cycloheximide)
48
47
-1 DNA
mRNA
-1
mRNA [28]
8
ATP
[1]: (1) (2)
(3)
(4)
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