选择性COX-2抑制剂的研究进展

，但若干研究表明长

期应用特异性

COX-2< /p>

抑制剂可能增加心血

管事件的风险，如 心肌梗塞、脑

卒中。塞莱昔布、罗非昔布和伐地昔布暴露出的问题说明虽然特异性

COX-2

抑制剂在胃肠道安全性方面有显著的优势，但长期用药的 安全性仍需开展

进一步的研究和评价

。

关键词

环氧化酶、

COX-1

、

、花生四烯酸、塞莱昔布、罗非昔布。

The Research Progress in Cyclooxygenase-2 And its Inhibitors

liguojun

Anhui University of Traditional Chinese Medicine,12331133

ABSTRACT

Ring

oxidase

(Cyclooxygenase,

COX),

arachidonic

acid

(AA)

converted

to

prostaglandins (PGs) enzyme important in the process of the speed limit. Its catalytic PGs in the

body

of

a

variety

of

physiological

and

pathological

processes,

such

as

inflammation,

fever,

the

coagulation process. In 1991 confirmed that the ring oxidase (COX), there are two subtypes: COX

- 1 and cox-2, ring oxidase (COX) there are two kinds of isozymes involved in the synthesis of PG

.

Inducible enzyme of cox-2 in arthritis pain and inflammation, and COX enzyme - 1 with gastric

and duodenal stomach protective of the involved in the synthesis of PG

. Traditional NSAIDs such

as

aspirin,

indomethacin

and

diclofenac,

naproxen, etc to

COXl and no

selective

COx2,

can

be

called a nonselective COX inhibitors (Nomelective COX inhibitor). Its inhibition of COX2 is its

foundation

treatment,

the

inhibition

of

COX

-

1

would

become

serious

whole

digestive

tract

damage.

Some

existing

NSAIDs,

low

doses

of

COX2

preferential

inhibition,

referred

to

as

the

1

propensity to cox-2 inhibitors (referential cox-2 inhibitor), such as the U.S. yesterday (meloxicam),

beauty

and

ShuLi

(nimesulide),

depending

on

the

degree

of

acid

(etodolac).

Such

drugs

the

clinical

curative

effect

of

nonselective

COX

inhibitors,

but

the

incidence

of

gastrointestinal

adverse

reaction

is

low.

Specific

cox-2

inhibitor

(specific

cox-2

inhibitor),

like

Mr

Selebi

cloth

(celecoxib),

ever

had

cloth

(rofecoxib),

vardenafil

yesterday

cloth

(valdecoxib),

Paris

yesterday

and

yesterday

cloth

atto,

within

the

scope

of

the

treatment

with

little

or

no

COX

-

1.

Clinical

studies

showed

that

specific

cox-2

inhibitors

of

gastrointestinal

security

is

superior

to

the

traditional

NSAIDs,

but

several

studies

have

shown

that

long-term

application

specific

cox-2

inhibitors may increase the risk of blood tube events, such as myocardial infarction, and stroke.

Mr Selebi

yesterday,

yesterday had the problems exposed by

the cloth and vardenafil

yesterday

shows that while specific cox-2 inhibitor has significant advantages, in gastrointestinal safety but

the safety of the medication for a long time still need further research and evaluation.

KEY WORD

Cyclooxygenase

、

< /p>

COX-1

、

COX-2

、

AA

、

celecoxib

、

rofecoxib

1.

环氧化酶简介

1.1

环氧化酶的结构

1994

Picot

等用

X

射线晶体衍射学方法揭示了

COX

的三维结构，证实

COX

在细胞内分布呈单向性。

COX

的结 构是由三个彼此独立的折叠单位构

成：

N

端的类似于生长因子的表面区域、膜结合区和

C

端酶活性区。

COX- 1

和

COX-2

均是分子量为

71kD

的膜整合蛋白

,

分别含有

599

和

604

个氨基酸

残基，

两者的氨基酸残基有

63%

的同源性。

Hawkey

描述了

COX

的空间结构

，

COX-1

和

COX-2

的活性部位都是由末端带有发夹弯曲的疏水通道组成

，

COX-1

与

COX-2

在通道的一侧的

120

位 有一个不一样的精氨酸（

Arg

）残基。

在通道另一侧的

523

位上，

COX - 1

和

COX- 2

分别是异亮氨 酸（

Ile

）残基和

缬氨酸（

Val

）

，但是

Val

的分子小于

Ile

，因此在旁边留下 一个小空隙，可

与很多药物建立共价结合。在通道的开口处的

513

位，

COX-1

是组氨酸

（

His

）

,

而

COX-2

是柔韧性更好的

Arg

，并且

COX-2

的开口比

COX-1

大，使底

物与

COX-2

结合更容易

。

< br>

1.2

环氧化酶的功能

< /p>

20

世纪

90

年 代末，研究者们确认了

COX

存

在两种同工酶，即

COX-

1

和

COX-

2

。进一步研究

发现：

COX-1

是参与正常生理作用的结构酶，参与

保护胃肠道黏膜、

调节肾血流和促进血小板聚集等作用

COX-1

是诱导酶，

在

生 理状态下，

体内大多数组织中检测不到

COX-