PPARγ研究新进展

promotion of em

ployment, form a rea

sonabl

e and orderly pattern

of income di

stributi

on,

buil

d a more fair a

nd sustai

nable

social se

curity sy

stems, medi

cal and health system reform. T

he plenar

y, innovati

on

of social gover

nance, must focus on the mainte

na

nce

of fundame

ntal intere

sts of the

ov

erwhelming majority of the

pe

ople, maximize fact

ors,

nha

nce

social development, impr

oving soci

al governance, the i

nterests

of national security, e

nsur

e that the

pe

ople live

and

work,

social stability a

nd

orde

r.

o improve soci

al governance, stimulati

ng social

organizati

on, i

nnovative and effective system of preventi

ng and resolvi

ng social

conflicts, im

proving t

he publi

c se

curity sy

stem, set up the

National Se

curity Council,

national security

systems and nati

onal

security strategy to ensure

national se

curit

y. Pl

enary

sessi

on, t

he

construction

of ecologi

cal

civili

zation, you m

ust esta

bli

sh systems

of ecological system, using the system to

protect t

he ecologi

cal e

nvironme

nt.

o improve natural

resour

ces a

sset pr

operty right sy

stem and

use

contr

ol, red li

ne of delimitation

of ecol

ogica

l prote

ction, resources pai

d use system and ecologi

cal compe

nsati

on system i

n ecologi

cal envir

onment

protecti

on ma

nagement system reform. Pl

enary sessi

on,

centeri

ng on buildi

ng a listeni

ng party comma

nd, can wi

n and havi

ng a fine style of the pe

ople'

s army, a strong army under the

new sit

uation of the

party Goal

s, restricti

ng the

development

of national defense and army buil

ding i

s solved outstanding

contradicti

ons and problems, i

nnovation a

nd

devel

opment

of military theory, enhance milit

ary strategic guida

nce, improve t

he milit

ary strategy in the

new period, buildi

ng a moder

n military force system wit

h Chi

nese characteristi

cs.

o deepe

n the a

djustment of per

sonnel system reform in t

he army, military policy a

nd system reform, pr

omote the

devel

opment

of military and

civi

lian integration de

pth.

Plenary session stressed that

compre

he

nsive reform must be to strengt

hen a

nd impr

ove the

party's leadershi

p, give full play to t

he core role

of the party commands the overall

situati

on and coor

dinati

ng all parties, improvi

ng the party'

s leadi

ng water ... M

argin. Challe

nged t

he leadershi

p of the

Communist Party of China, M

arxism- Leni

nism and Ma

o Zedong thoug

ht by Deng

Xia

o-ping's fla

g, replace

d by thr

ee repre

sentatives a

nd the harmonic

society.

The former Communist Party spirit and social cohe

sion point of almost all politi

cal makeover. Characteristi

cs of sociali

sm public

ownershi

p is shifting to private ownership, pla

nne

d regulati

on a

nd market regulation, the proletari

an regime controlle

d by the e

lite. Of universal e

qualit

y, fairness and

ba

sic pri

nci

ples

of distribution system is sociali

st society,

how

ever after economic m

onopol

ized

by powerful, veste

d interests gr

ow, em

ployers

do

not have t

he same status, har

dly seems fair social

distribution.

State key protection of ca

pital interest

s rather tha

n the intere

sts of citizens, had

bee

n hits t

he bottom of the pr

oletariat

PPA Rγ

研究新进展

过氧化物酶体增殖物激活受体

(peroxisome proliferator-activated receptor, PPAR)

是

调节目标基因表达的核内受体转录因子超家族成员

[1]

，

1990

年

Issemann

等

[2]

首先

发现了这种能被一类脂肪酸样化合物过氧 化物酶体增殖剂

(peroxisome proliferators, PP)

激活

,

而被命名为

PP

激活受体

( peroxisome proliferator activated receptor, PPAR)

。

根据结构的不同，

PPAR

可分为

α

、

β(

或

δ)

和

γ

三种类型， 其中

PPARγ

主要表达于脂肪组

织及 免疫系统，

与脂肪细胞分化、

机体免疫及胰岛素抵抗关系密切，

是胰岛素增敏剂噻唑烷

二酮类药物

(t roglitazone, TZDs)

作用的靶分子，成为近年来研究热点

1.

PPARγ

的结构及特征

基因位于

3

号 染色体短臂上

[3]

，

含有

个外显子。

由于基因转录时所用的启动

子和接拼方式的不同，

PPARγ

可以分为

γ1

、

γ2

和

γ3

三种亚型，其中

γ3

< br>和

γ1

编码

的蛋白质相同

[4,5]

。

PPARγ2

< br>编码的蛋白质由

505

个氨基酸组成，

< br>比

PPARγ1

在氨基

端多

30

个氨基酸。进一步研究发现

[6]

，

PPARγ1mRNA

是由

8

个外显子编码，而

PPARγ2mRNA

由

7

个外显子编码，编码的氨基酸数量虽有不同 ，但两者

PPARγ

的结

构域、

DNA

结合域及配体结合域等完全相同，作用基本相同。

研究发现，不同种属间

PPARγcDNA

具有高度同源性，如人与小鼠的

PPARγ1

的一致

性达

91%[7]

。在啮齿类动 物中，

PPARγ

主要在脂肪组织中表达，而在人体，除脂肪< /p>

组织外，在巨噬细胞以及其他脂肪贮存细胞，如肝、肾、肺及直肠中均有表达，并且人

肝组织比鼠肝表达更为丰富，

而肌肉组织基本不表达。

PPARγ1

是

PPARγ

的主要形式，

表达范围相对广泛，

PPARγ2

表达范围较窄，主要在脂肪组织中表达，

PPARγ3

仅表达

于巨噬细胞和大肠中

[8,9]

。

2. PPARγ

的配基和功能

PPARγ

的配基

(

又称激动剂

< br>)

有两种

,

生理性配基和药理 性配基。

生理性配基有

15-

脱氧

前列腺素

J2 (15d-PGJ2)

及其 代谢产物和不饱和脂肪酸等

,

药理性配基有胰岛素增敏剂

噻唑烷酮类化合物

(TZDs),

它是

PPARγ

的高效配基。随着研究的不断深入，越来越多

的配基不断被发现，

Lehmann

等报道吲哚美辛 等非甾体类抗炎药也能与

PPARγ

结合

并使之活化

[10]

，此外胰岛素可活化

PPARγ

，大鼠脂肪细胞经胰岛素处理

30min

后，

能使其磷酸化水平增加

3

倍，显示

PPARγ

活性升高

[11]

。配基与

PPARγ

结合后< /p>

,

可激

活

PPA Rγ

并调节目标基因的转录活性。

PPARγ

的

N

端功能区含有一个能被有丝分裂原激活的蛋白激酶磷酸化位点

,

若该区域

突变或在磷蛋白磷酸酶共同作用下则不能产生磷酸化而 使其活化

[12]

。配体与

PPARγ

结合并使之激活后

,

与

视黄醛

X

受体

α(retinoid

X

receptor

α

，

RXRα)

形成异二聚

体

,

再结合于特异性

DNA

序列而使靶基因活化

,

此序列称为< /p>

PPAR

特异性反应元件

(peroxi some proliferator responsive element,

，< /p>

PPRE)[13,14]

。

PPARγ

还能影

响

NFκB

、信号转录子、

激活蛋白

-1

介导 的信号通路，通过抑制这些途径的激活达到抑

bvi

ousl< /p>

y, face

Chi

na's Socialist sy

stem, the Communi

st Party is not the

party.

In that

case,

politi

cal chaos ha

s bee

n very tight. Is remodeling

or reconstr

ucti

on, i

s a corr

ection or a

stove.

Whet

her to tur

n right or l

eft, is ba

ck to the

source

or put forwar

d ne

w political i

deas.

This is to determi

ne the road

probl

ems in

Chi

na, is al

so the key out

of the de

ep water

of the reform of the e

conomic

system.

After 18, the new Ce

ntral collective le

adership atta

che

s great importa

nce t

o political

orientation.

Fi

rst, the

cles

starting point, starti

ng from the Ce

ntral

Governme

nt's self

-restraint, w

hich prea

che

s and pr

o-image,

brought fresh feeli

ng to the

community.

Secondl

y, before reform a

nd ope

ning

up a

nd reform and openi

ng two

periods after non

-negative,

untyi

ng the tangl

e of the soci

ety a long time on t

his issue. Third, a new ge

neration of part

y leaders

on various

occasi

ons t

o Mao Ze

-Dong a

nd M

ao Ze

-Dong's thoug

ht of evaluati

on

has room for manoe

uvre,

throug

h to the r

uling i

deol

ogy of Ma

o Zedong thought, i

s the

call of the

soul to the S

ociali

st Revolution and constr

ucti

on. Em

pty talks jeopardize national intere

sts and try again, i

s an affirmation of De

ng Xi

ao

-pi

ng's reform ideas.

These strong politi

cal sig

nal showi

ng a ne

w generation of poli

tical leader

s is still kee

ping to t

he Socialist roa

d.

Four is revisiting the

o Ze-Dong's hi

storical

cycle

of

ofile anti

-corr

upti

on a

nd the importa

nce

of the Constit

ution, reorganization is ba

d style

of officialdom, was to

civilize people obey the la

w, w

hile improvi

ng the

col

or change of the regime

of vigilance.

Five is to reform into deeper w

aters and stressed that top

-level de

sign, t

his is a revie

w on the reform and openi

ng up in the

past, is

also l

ooki

ng for a way out.

Six foreign and Russia

closer, t

he flexible attitude on the issue

of the Korean

pe

ninsula, Si

no- Japanese fishing hardline China

on the i

sland out of the

nt

ow pr

ofile sha

dow bega

n to gradually pla

n

development. Signs show that t

he new l

eader

shi

p bega

n to make a left turn in politics.

However, as of right now,

not only ide

ologi

cal confusion in the community, t

he ne

w leader

shi

p's thi

nking is me

ssy.

New lea

ders

both

stresse

d the

nee

d to implement t

he Constit

ution, stressed the

nee

d to turn

off the power i

n a cage. Al

so stre

sse

s that Mao Ze

dong thought

cannot be l

ost, 3

0 years after the reform and

ope

ning

up 30 year

s ago ca

n not de

ny each other.

Both a

dvocate democracy a

nd rele

ase

n does not speak of

cal constrai

nts. Neither

deny the history

of the CPC Central Committee on several issue

s ...

Comrade

s: today bring

s together members, mainly i

n order t

o provi

de a platform to Exchange a

nd le

arn from each other in or

der to facilitate our work. Just now, w

e focus on taxation, pl

anning and stabi

lity, safety,

proje

ct constr

ucti

on, typi

cal topics such as

private facts pre

sentation and intera

ction, and towns currently exist in the in

-de

pth a

nalysis

of the problems to

be solved, t

o explore

new methods to solv

e the pr

oblem.

It can

be sai

d that summing up t

he achievement,

no gra

ndsta

ndi

ng; ana

lysis