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????????ALT????1000U???????????????????"?????????????"?????????. ??: ???????(drug inuced liver injury, DILI),????????,???????/??????????????????????????????????????????,???????????????????? ???????????,???????????????,????????????????????????????????????????????,??????????2%,??????????

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2007.7

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2007 7 1347541

2007.7


2007 7 1347541

ALT1000U


2007 7 1347541

drug inuced liver injury, DILI

21020


2007 7 1347541

1.

2.

3.

4.

5.

6.

7.

8. ADR


2007 7 1347541


2007 7 1347541


2007 7 1347541

900

20-40%

3-9%

Lewis JH. Drug-induced liver disease. Best Practice of Medicine. January 2000.


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Sgro1997200081301

14 /100,000DILI

  • 12% 6 %

    DILI16

    Hepatology 2002;36:451-455.


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, . . , 2004.3, P514


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1015%


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10

40

90

60


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1525

50

50%

25


2007 7 1347541

(1)

Michael F.Sorrell Schiffs Diseases of the Liver2003


2007 7 1347541

(2)

Michael F.Sorrell Schiffs Diseases of the Liver2003


2007 7 1347541


2007 7 1347541


2007 7 1347541

  • I

    • -OH -SH-NH2 -COOH

  • II


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1P450(CYP450)

CYP450

CYP1

CYP3A4

CYP2C2

CYP450

CYP450


2007 7 1347541

1P450(CYP450)

CYP450

P450CPY1A2CPY2CPY3A

P450

P450


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1P450(CYP450)

CYP450

CYP450

P450

CYP450


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2

2

2S

21

21


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2007 7 1347541

FDASFDA


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P450

O2

Ca++


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()

, 2-


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1

1

1,

2


2007 7 1347541

P450

P450

CYP450


2007 7 1347541

P450

P450

CYP450


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1

1

1,

2


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1

1.

2.

3.

4.

5.

6.


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2

1.

2.

T

3.


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3

1.

2.

28

3.

4.

P450 2E1GRP94

5.


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2007 7 1347541


2007 7 1347541

6


2007 7 1347541


2007 7 1347541

ALT

GGTALP


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1-5

1

ALT

2~330


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  • (6%)

  • ()


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2007 7 1347541

2000


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2


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1.

2.

3.

4.

5.

6.

7.

8.


2007 7 1347541


2007 7 1347541

1.

2.

3.

4.


2007 7 1347541


2007 7 1347541

1.

2.

3.

4.

5.


2007 7 1347541


2007 7 1347541

1.

2.

3.

4.

5.


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1.

2.

3.

4.

5.

6.;

7.

B6


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1.

2.

3.

4.

5.


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2007 7 1347541


2007 7 1347541

6779


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2007 7 1347541

1818


18 18 c 18

1818C18

C-18

C18

18

18


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1999131

20032312


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2007 7 1347541


2007 7 1347541

%

0

40

60

80

20


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Ca2+

1997.7168


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*p<0.01

18H 200110929


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P450

18P450II 200136(5)321 324


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GSH

*

*

* p<0.05


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N10

P 0.01

P

GaIN


D galn sod

D-GalNSOD

** p

n=10 ** p<0.001

GaIN


D galn nos

D-GalNNOS

* p<0.05

n=10 * p<0.05

GaIN


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P450

P450

GSH

GSH


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P450

O2

Ca++


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2007 7 1347541

GalN


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MgIGGalN

() 0

() +++ +++ + ++ +++ +++ ++ ++ ++ +++ 2.4

60mg/kg ++ ++ + + +++ ++ ++ +++ + ++ 1.9*

15mg/kg +++ ++ ++ ++ +++ ++ + + ++ +++ 2.1*

30mg/kg + ++ +++ ++ ++ ++ + ++ 1.5**

60mg/kg ++ + + ++ ++ ++ + + 1.2***

N =10,* p > 0.05; ** p < 0.05; *** p < 0.01


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  • 462

  • 17

    Vc

    100mg

  • 29

    Vc

  • 4


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*P<0.01

#P<0.05

*

#


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  • 924646226249+(DA)45mgm23d150 mgm27 d

    • l50mg+5250ml11

    • 1d8

  • ALT>45 UL


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13

13

8.7

8.7

4.3

0

0

ALT1343.5 P < 0.05


2007 7 1347541


2007 7 1347541

Thank you!


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