??-????? (Ischemia-reperfusion injury)

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??-????? (Ischemia-reperfusion injury)
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??? ??
Clinical practice

• ???DIC?????
• ????????????
• ????????(?????????)
• ?????????????
• ??????????????

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??
???????????????????,???????????????????
????(ischemia-reperfusion injury)? ?? 1.???? ?
?????2.???????
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???(calcium paradox) ???(oxygen paradox)
pH??(pH paradox)
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??? ????(mechanism)

• ?????(Free radical)
• ?????(Calcium overload)
• ????????(Effect of WBC,leukocyte)
• ????????????
• (Lack of high-energy phosphate compound)
  
• ????????(endothelin)
• ???????????(angiotension ?)

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?????
(?)????????
??????????????????????????????
1.???? 2.?????
O2
O2
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(?)??-???????????????
1 ? ????????(??????)

• ??????(XO) 10
• ??????(XD) 90
• XO xanthine oxidase
• XD xanthine dehydrogenase

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Xanthine oxidase,XO
ATP ADP AMP ?????
??????(XD) ??????
??????(XO)
???? ???O2.-H2O2
O2
??????(XO)
??O2H2O2


OH.
???
Ca ATP
???????
???
????
O2
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• 3  ???????
• ???ATP ?????Ca2????????????
• ??????
• O24e?H2OATP
• O2e? O-2 e ?H202e? OH e?H20 O2e ? O-2
  
• Ca2??????Mn-SOD?? ??OFR????

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4. ?????
???
???
CA
????
???
O-2?
(???80O2)
?????
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Organic substance O2
Synthesis Metabolism Transport Muscle
contraction Transmit
oxidation
ADPPi ATP
energy
energy
H2O,CO2 (carbon dioxide)
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(?)OFR?????

• 1. ??????(lipid peroxidation)
• (1)????????
• (2)????????
• (3)???? ATP????

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2. ?????????
???-?????
??-?? ???
????
?????
-S-S-
OH
OH
HO
HO
CH3-S-
??-????
O
?????????????MDA
??? ??
?????
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3. ????????
80?OH???
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?????(calcium overload)
??????
Ca 2
Ca 2
Ca2 B Pr
Ca2?
Ca2
Ca2
SR
Na -Ca 2??
Mt
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?? ???Ca2 10-3mol/L ???Ca2
10-7mol/L ???Ca2 ????Ca2 10000?
??ATP??? ???
Na-Ca2????
???
????
???(SR) ?????(CaBP) ?????
???
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(?) ??????
1. Na -Ca2???? ??Na??H??NE- ?1R-
PLC-PKC 2. ?????,???? ? ?????????OFR
3. ?????
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Na-Ca2????(?????????????) ??3?Na
1?Ca2 ???? (1)??????? (2)??????? ????Ca2
ATP Mg2
Ca2
3Na
K
Na
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(1)????Na????Na-Ca2???? ???
ATP??Na??????Na?? ??Na-Ca2?????Ca2????

ATP?

Na?
Ca2?
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(2)????H????Na-Ca2???? ??Na/H??????????H??
??? Nao Ho Nai
Hi ???????????H?? ???????H????????????
H??????Na/H???????? Na?
???? ??Na-Ca2????
Na
gt
H
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??? H?
H?
Na?
Ca2?
??? H?
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(3)PKC????Na-Ca2???? ?a1?????????G??-PLC
?H /Na ????
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(?)?????????????? 1. ??????? ??Ca2?
?????? ???? ???????
ATP??????? 2.?????? ?????
??????????? 3.???????? ????????
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4.???????? ??XO 5.????????? (1)????Ca2
(2)???????H??????????
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• ?? ????????????
• (?)??-????VEC??????
• VEC????? ??????????
• (adhesion molecule)
• ??????????????????????????????????????
  ?,????????????????????????????????????????????????
  ??????????????

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???? ????
??
???????
CAMs ??
??(PAF?LTs)
?? ??
??
??????????
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(?)??????????????

• 1. ?????
• ?????(no-reflow phenomenon)??
• ?????????????
• OFR????????
• ????????????
• ????????????

???
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No-reflow phenomenon

• Rheology(is concerned with the flow and
• deformation of materials experiencing an
• applied force).
• Microvascular calibre
• Membrane penetrability

2.????
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??? ?????
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?? ????-???????? (?)????? 1.???????? ??
???????? ????? ????????
ECG??????????ST???,R????
???R??????,ST?????? ??,Q???,
????
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• ????
• ????
• ???????
• ?????
• ???????????????
• ????
• ??????????????????? ?,???????
• a-R?CA??????????????
• KATP??,???????

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2. ???????CO? ????myocardial stunning
,?????? ????????????????????????????????????
????????????????????
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Stunning
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(?) ?????? ATP?CP??,????????.
(?)???????? ?????,?????????,????,
???????(????,???,??,???.)
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• ?? ???-????????
• (?)??????
• ATP CP G ??????
• cAMP? cGMP?

?????
??????
???????
? ?????????????? ???? (?)?????
???,?????.
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Brain ischemia/reperfusion injury
Brain ischemia energy substance
lactate
Peroxide reaction
cAMP cGMP
PLC
Phospholipid lysis
Free fatty acid
cAMP cGMP
reperfusion
Free radical
Injury
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??Intestine ischemia/reperfusion injury
?????,????????????????????????,????????????
?? ????????,??????????????????(????)???????,????
??????????????????????????????????????,????,?????
,???????,?????????(???)?????????????,?????????
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??? ???? 1 ?????????????? ??????????pH????
?? 2 ????????? ???????????ATP 3
????? (1)??????VitE VitA VitC ????GSH? NADPH??
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(2)?????SOD CAT? 4 ????? Ca2????? 5 ??
????????? ??????