免费文献传递   相关文献

Mitochondrial dysfunction induced by excessive ROS/RNS-metabolic cardiovascular disease and traditional Chinese medicines intervention

过量ROS/RNS引发的线粒体功能障碍与代谢性心血管病及中药介入



全 文 :#{|
#
¡·
3T1Z3>1
“[nÍþÞgÑÒi
ôӛßQРGrÇ}Ð
E¾¾
P
#
¼¿
P
#
ÀÁÂ
P
#
%|
P
#
ÃÄ
P#W
!
!Pf
¼c9ILB¯ NO9LéÏñMN90
#
¼c
WMPWMO%
Wf
i<´PÛB¯ QÛRI¯K SFAÛLLò¯þ
#
´PÛB¯ T·I¯MNO
#
i< QÛR
@+[[MOM
$
‚;
%!
ôӛßQРC´þبJYôÓTUê‚& ª[|¨ßQÐM 
!
ªr
W
âØ  »CÒâ[ô
ӛM 
!
(Y—äͱä㓬—”¡
!
-iʂ–#@\è‰

ñƒ›R
Z
ƒ›jäã[R\\äC“³Ê‚–#@[|i&ª—
!
fnÍþY—Cƒ›R
Z
ƒ›j[;¬
!
-CªE›`-
!
RèÆ)¼.
!
nÍþÞgÑÒCQ¿ßQÐÀ
Á[| ´Ü

7œ±ƒ›R
Z
j²“[nÍþÞgÑÒм
!
}z/üF¡·¾²ä[nÍþ¶Àm+Aʂ–#@
\[ef
!
nüFm¡efYôÓGP
W
âØ  
!
¼fäãßQÐM ³|š£
!
>}z/Ö!
#
.—>
#
±
#
wêÑ
tCO‡(ZrÇm¡¡
3T1Z3>1
GefnÍþ¶Àm+
!
±fkh1KE›

f*_˜Zrǐè˜û¡VÑ¡™š
‡E›
!
ènËÒ)ÇE›[H|›
!
u½/rÇE›[™T›

$
‰Š‹
%!
ƒ›R
Z
ƒ›j
&
nÍþÞgÑÒ
&
¶À
&
ʂ–#@&

$
8Œ$f
%!WMPMMNMWMML
$
Ž E p
% !
­æö÷ Ø
)
ÿ|A
*
ö ÷ Ý P . ç u v
$WMMX7=:PP7MN;MO%&
_&S;ø…ø|R\ji¸ºÀ]
-
ƒ„A
.çuv
$-;M^MPM%&
_&Söø­1÷ÑK^uv
$MN^OM[PPOMM%&
_&SöørÇRô\uv
$MNRcP_[WPM^%
$
€>
%!
!
›½
!
;<
!
89ãQó
!
‚&±×ßQÐÇ¥ƒ„N
E
!@(&. $MWP%LPOWWLOL! -;I$&. V$b$)O\*I$&fG/I
$
>‘’
% !
=((
!
’9ƒ„ã
! @(&. PONPXON[OM[! -;I$&.
#`$)*G#()G#()fPXNN\PXOfG/I
!!
nÍþC±²ôÓ[rœ

±þ±²ÄÚ[|„h|
„Aã *tYr
!
è
WMg hOMg
Œ]nÍþr
!
¬ln
Íþ
R>=
[
PO
 *tYû°inÍþ~[.„!Ñ
ãÚ
=@8
љi&ã?ôÓ+sŒèünÍþ[K
;Ú

nÍþ`Cž|wèlñ[sªÙ
$I2R>=%

²à

ž/g·KOÞgg®
!
nÍþãڃ›Rlñ
s
#
i¨©±²[R\ÈÎ\ÑnfKQ‡

¯nCñ
nÍþO~±²¶Àª„f]±²¶Àr³‰ŠE›

òföƒ[×
!
d;d™[ƒ„u½
!
]
W
âØ  
#
ʂ–#@\›ßà‡S1›M rnÍþ[ÞgÑÒ
iavM [‰F3E
!
>CavM  ´Ür[i&…
T

¤7±¡·
3T1Z3>1
ä“nÍþÞgÑÒм
!
}z/ñ.²äƒ[nÍþ¶Àm+
!
]Ê‚–#@\ê
Òâ[ôӛßQР[ ´Ür[E›
!
>•¶rÇ}
Ð
$
JÇÜ
%
¡·
3T1Z3>1
ä[¶Àm+
!
;1Kôӛ
ßQР

!3T1Z3>1
inÍþÞgÑÒ[‰F
nÍþC±²èRôÓÑãڃ›Rlñs
$3T1%
[
‰Šû²

nÍþ´G2.„S¯*äã Rlñs
$T
Q
/
W
%!
Öf*ãڃ›R
$3T1%
±²~ÑnÍþ~™ 
¡R\Fã*¨©nÍþ
3T1
[ãÚ
!
±f¨©/»Ÿ
㥶qª±²~
3T1
[)Ä

nÍþ
3T1
`ì[Þô
!
Úê´þäãM Ñ“÷ø[i&ª—

љø÷›ÊɛM ÑôӛM 
!
RŒ] DÃà
Qc˜*ÑÒÑÙNª…Q…RJÚQR6M
$8T
W
%
ªÊ

ÎnÍþ
8T
W
ªÊ­
MfP hMfW II.*
7
!
nÍþR\:@ÞgÓ«F


:
R\â
Z

:
Èâ
$>=RZ>=R.
p
%
YgÖã
!
¿ §FãghÇÜ
!
±fÇÜ45Ø
#
žG}
þÖЃç@˜*

nÍþèRR\…}µog·[¡
ÙãÑÒ7
!
Kf,RŸÿ…}ê´þµog·
!
Q¿
x·ƒ@ãÚ
!
ƒ@]±²~x·ÔU
!
Q¿±²~@rp

±²~@rp“x·
$
Wp
Öб²~
!
Q¿±²~  
è
!
Q¿nÍþ¥ãY*ËÀÁ
!
£¤Q¿nÍþÞgÑ
Ò

nÍþ
R>=
A…R›Ÿ½ 

]úv ¥j´ª
!
±
²~¡R\̧G|v¡R\6„ûÄÅlÆѨã—
-
YgÖ¥x·³U[ƒ›R
!
Öa_nÍþrŒ]| ¯°
[|R\jÄÚ§
!
gh…R‡®]ä¾äè¡·[
>T
äã
!
ƒ›RÑ
>T
0Ääホj
!
|ÚQ¿nÍþÞg
/OW^W/
{
OX
ï{
P[
•
WMPP
÷
_
²
!!!!!! ! ! ! ! ! !!!! ! ! ! !
S/&fOX! :004(!P[
1(U2(Ib(%! WMPP
Ñ[6„ ¥]s©

#3T1Z3>1
AnÍþ±²¶Àm+[efGªiʂ–
#@\[‰F
#]!3T1Z3>1
inÍþ¶Àm+y}
!
ñnÍþäã[
ƒ›R
Z
jlñs
$3T1Z3>1%!
AnÍþ~¶À*t[ef
C(©
3T1Z3>1
E›´Ü[i&*©

±²¶À‚&ñâ¶ÀÑ¡¶À*tÐZE›>¨Ú
[

¡¶ÀÚ@
7G&;W
Ñ
7G&;+
B
6XŒ]nÍþ®¥
#
~
Y¸¥Ñ*¥
!
]±²gh¶Àä¾

¡¶ÀÚ@*ã
:@\½¡Ñ*tY‹ÿ

nÍþ®¥r[
7G&;W
Ñ
7G&;+
B
Œ*…*tä§:@\JË
G$0U$0(
Q\,ÿ
7G&;W
Ë*
t§Q\,ÿ¾|KDêâ¶À*tY6„
!
ªf*ä
A2G
O~
!
â’·Î!
äã¶À

ìÔI~Y¸¥Ñ
*¥[
7G&;W
Ñ
7G&;+
B
!
*giúv›nÍþ¦ü[±²¶
Àrsè‰

â¶ÀÚ@‚&wx
75!7$K!7$5
Ñ
7GB;+0
‡
!
‚&6
띱²r
7$K
C£ÃR[â¶ÀÚ@
!7$K
]»Ÿ
±²r‚&ÔI±²

&é]nÍþ_`RèØ6
7$K
Œ]
!
ì
7$K
6„>›±ÐnÍþ®¥~fC\uQ
fnÍþ¼T

Aâ¶À*t[ª¸Ú@
!
û
7$5!75
‡Œ‚&Œ]±²r
7$V
CüýR[—è[|
!
ÔInÍþ[â¶À*tYÚ@

ìC
!7$V
]»Ÿ±²
r>Y¼Râ¶Àƒ›
!
*gCªê]nÍþ®¥r[
7$V
i
7G&;+
B

!
fͪƒ›…ÇÜ

±²gh¶Àä¾
!
7$V

>
©€>ã1iD!7$V
&i
7G&;+
B
6!
!
O~K;[
7$V
(¼ŽB]nÍþ®¥~
!
>iäƒ[
75

!
0•Q¿
7$V
äƒ>|Ú
A2G
[rKm–
!
Í
A2G
±nÍþO~­±²c
!
>]0Ä
=U$6;P$$U/U2/2GU%/2($0(
$G2D$2)*6$G2/%;P%
¾¬Ê
G$0U$0(
’·Î!
Ó
A2GZ=U$6;P
jÄÌäƒ
G$0U$0(;_!
¾FÖäƒ
G$0U$0(;O
Ѫ¸ª6
G$0U$0(!
±f“³±²¶À

nÍþCm¡
8@8$U(%I($b&2A2%$)02/) U/%(!8@8%
;
¨©ªª«›Ñ¶Àª„[O~[

]¡¶À[‰Šª„
$7G&;W!7G&;+
B
Ñ
7G&;E%
Ñâ¶À[‰Šª„
$7$K!7$V!7$5!
7I
Ñ
75%
r
!
|²¶Àäª—KR
!275
nâÍ
7$KZ7$V
ã&#Î\Ñ¥±Ð
!
Q¿xW|Ú


!
èƒ„¼
.
!275Z7$K
PQ[nÍþª«›Cm¡Ñ| …Pê
@T<
jÄþ[®¥Þg›K^§[jNE›;¨©[
P(

3T1
i
I2R>=
ÀÁääƒnÍþ~Ø[¶Àm+
!
âÍ®¥[ª«E›G±²{—

[O~
#
¶ÀPQª„
=:J$$U/U2/00;)54G)*6$G2/%%
J
1I$GZR$b&/$0(G/)5 I2/;
G#/)5%$;5(%D(5 $G2D$2/%/6G$0U$0(0Z5%(G2:=8b)5)*U%/2()
/6&/EU:%
±nÍþh²[4I

_Rg“¸Å @
8!§¦üJ›¸Å @8!§¦ü[²~nfKQ

]
¸Å @8!§¦ü[nfm+r
!
±²{—

i¶À*t
§ƒ\ª„
=U$6;P
|Ú¶ÀjÄþ>òÓr®
U%/G$0U$0(;
_!
PQª6[
G$0U$0(0;O
Ñ
;[
[6,


!1I$GZR$b&/
A
¡
:=80
[ÇÜé!
âָŠ@8!§[ƒ =:J

±²Yh²*[4I;¨Ú›¸Å @8!§¦ü[nf

!
>PQ±²*?{þ[<¢Ñ
R>=
[6,
$
d
P%
d
P!
nÍþ¶Àm+
#]#3T1Z3>1
“[nÍþ¶Àm+iʂ–#@!
nÍþ~[
3T1
äÌ[¥™Y—Q¿
I2R>=
ÀÁ
!
`ef
nÍþYÑ*tY[`Ô
!
AnÍþ¥JÚY*Ë[À
Á

ÍnÍþèRR\ÞgãÑÒ>äã-™[
3T1!
Í
QÐ)À¢±²¥ãsª¡¼k
!
PQª¡¥Z>iª

!
ÍßQÐ~CY¥¤
!
i.Z7PQV¢±²¶À
!
Jږ#@\ÀÁ
W(

]ʂ@\ÀÁr~G±²
#
QÐ)
À¢±²
#
¸º±²[¶À(·iÀÁÙÚ»D
!
Ö|›
µ½/¶À]Í4[>£Ñô,r³f‰Š[E›
O(

R\Þ3*t
TK;BRB$/K5`(5 &/E;5()02A;&U/U%/;
2()!TK;BRB%
Co|PQ±²¶À[i&ÌY
TK;BRB
*m¡¾DnÍþ¥.Iѓ³
A2G
O~f“³QÐ~
G±²[¶À

”;R
!TK;BRB
PQ[ߢ±²¶À
Gh
W
¶YZ[ ¦ünÍþm+

{|¶m+Cñ8!
 @¯E[¸Å @§
$G$0U$0(%
äƒ[
!
‚&O~
275
a
¶m+|²…äƒ*Í
8@8
—~
#
±²{—

O~
!
ò¾ä
ƒ¸Å8!§
;N $G$0U$0(;N%!
>Ö|›äƒ¸Å8!§
$G$0U$0(;O%
ͱ²¶À

o|¶m+C›¸Å8!§¦ü
›m+
!
ñâ¶Àª„
7$K
J
7$5
[O~²¨Ú
!
`gâÖ
±²{—

[O~
!
ì×i
=6$6;P
|Ú¶À6þ
!
gäƒ
¸Å8!§
;_ $G$0U$0(;_ %
òÓ䃸Å8!§
;O! X! [
$G$0U$0(;O!X![%
PQ±²¶À

nÍþgäã
>T!
>*
>T
C Rì!„[i&¨
Úª—
!-@$(&(G2%/) 2%$)0U/%2G#$)!-@%
ZèљÍsƒ
›rß
!
]»Ÿ[ã¥<
!>T
gm¡Çܱ²{—

R;¨©nÍþ[R•
!
gA
3T1
äãA¡E›

ì] ¥
/^W^W/
{
OX
ï{
P[
•
WMPP
÷
_
²
!!!!!! ! ! ! ! ! !!!! ! ! ! !
S/&fOX! :004(!P[
1(U2(Ib(%! WMPP
ëìª
!
¡™[
>T
DÑ Rì!„
$T
Q
/
W
%
|Ú¡RöÍs
$T>TT
Q
%!
gA*tY[¤ @æs|ÚY*Ë[R!
Í
§ƒ›¥ª
!R>=
ÀÁ
!
nÍþ[ž›¦hôõ
^(

$3T1Z3>1
iôӛßQР
”;胄u½
!
nÍþ]ʂ–#@\×r³‰Š

!
ªnÍþR\äã
=@8
ÞgÑÒ²O~[¡·
3T1
䓳ßQÐ[¸ºÎ\>Q¿Ê‚–#@\›ÀÁ[Ö
|›aµ
L;X(

-è¬F
!
nÍþ
3T1
[¥a*Í~GÞ
gTU
#
ߢ)À¢±²¥ZÑV¢±²¶À
!
a#|;
!
Ê
‚–#@\ÀÁäaµ
!
f*Í4`èô,[©Å
[(

W
âØ  CÒâ[ôӛM 
!
x·ƒ„Æ)¼.
!W
âØ  Ñ“¬—”¡RinÍþÞgÑÒè‰
N;_(

ñn
ÍþÞgÑÒ²“[“¬—”¡`䓳ßQÐÞgE
Ÿ>¼ª¸ßLQÐM 
!
}ªCʂ–#@
Ã]
WM
¾ö
_M
÷ô
!?$%5)/
‡
PM(
Ar‚Ê‚~G±²[§¨
nÆ.…QØä¥a
3T1
[äã
!
ºS÷¾
!
Z|ƒ„6Ù
[ƒ„0•u½
!3T1
[¥a‚&;¬ƒç@˜*
PP(

i»Ÿ±jD
!
u蓬—”¡[±-4&
W
âØ  Ñ˜
ûʂ–#@\g¨[ßQÐM 
!
²
!
ºèYAnÍþ
Þg[Sٛ1KVä謝˜ûʂ–#@\g¨[ß
QÐM [À1
PW(

8ù•ÑR\Þ3*t
$/K5`(5 &/E;5()02A;&U/;
U%/2()! /K;BRB%
Rg“³nÍþÀÁ
PO(
!WM
™÷hnè§
¨Æ.›…8ù•¡O[æËènÍþÞg[ÀÁ
P^(

i
ª¨e[C
!
…8ù•äÍßÃ܁[
I2R>=$I2/G#/)5%$&
R>=! I2R>=%

PL(

ÖÐV¢±²[6!8ù•
$6%((
G#/&(02(%/&! J%!
inÍþÞgÑÒè‰
PX(
/K;BRB

䃴G2jÄþ
:#(>T1
[ÿ©·Ñ
>=R8.
[R\;ä
ã
3T1Z3>1
P[;PN(

“¬—AßÃ[o|i&E›C¥aߢ[Q¬Ñ
¨exëʂAQÐÙ=[”¡
P_(

~G¦ü›QÐÙ=
ÞgÑ45ØJgN[ÀÁŸeòߢ~Y[ÔU
!
a#
Ö|›aµ/
W
âØ  Ñß÷
WM(

¶Ð“¬—”¡i~
GÞgTU[‰F·…6X‰?
WP(
!
ìnÍþ]~GFã
[Þg(Y¬./

éf
!
~G±²nÍþ]R…TDèfi&E›
!
>*Eê±²~
$
Wp
Ñ
>T
[¨Ú
ª—
WW(

ñ~GÞgÑÒ²“[…QØ
!
*m¡ÇÜn
Íþ~¡™[
3T1
ãÚ[…”&hÚÜ

%
|R\j
$>T%
iôӛßQР
hTÏ˵GnÍþi
>T
äÌ[¨ÚE›
!>T
Cn
Íþ´G
#=@8
ÄÚ[3]¨©ª„*ääã˜û¡RöÍ
@‡[
3>1 >T
Cñ|R\jÄÚ§
$)2%G/K5(0A)2#$0(!
>T1%
ÄÚ[
!>T1
|Ÿ*6ê
O
¨
.)>T1$)(4%/)$&)2%G/K;
5(0A)2#$0(!)>T1%!(>T1$()5/2#(&$&)2%G/K5(0A)2#$0(!
(>T1%
Ñ
>T1$)54Gb&()2%G/K5(0A)2#$0(!>T1%
ªr
(>T1
Ñ
)>T1
ãPê
G>T1$G/)02242D()2%G/K5(0A)2#$0(!
G>T1%
£”胄u½
!
]nÍþ~è| Šâ[
>T1
öâ
!
…Pê
I2>T1$I2/G#/)5%$&)2%G/K5(0A)2#$0(! I2>T1%!
f*
I2>T1
]ŸÃ
#
xL
#
ßÃ
#
ÜÃ
#

#
TU
#
ÃÑ¢
]ÙNrRè6ë
WO(

Rè[ƒ„Ͻ
I2>T1
wèi
(>T1
j”[01ƒ›
!
>*]…R7ªƒ›D»Ÿëìª
[&…Ñ™
!
>inÍþ[Þg¨©
WO(

nÍþm¡
$
Wp
½ ›[
I2>T1
;äã
>T!
>m¡i
A2G
R\§[*
ËÎ\;¨©nÍþ[Rá•Ñ#¥.I
!

>T
i R
ì!„J¡RöÍ@KÎ!
VäAnÍþ~[½ ›`6
„äãY*Ë[½¡
!
±fPQäãR\J¡RöÍ\\ä
ÎW^(

nÍþ×&
>T
;AôÓ³9±¨Ú
!
>.¨©
ã¥Þg
#
±²ò•ƒ›Ñ¶À
!
²èavƒ›Rèü
I2;
>T1
äã[
>T
[`ì<
!
…<[
>T
äQ¿
T>TT
Q
¡
™
!
ÍnÍþ
#
±²*tYѝYöÍZ
Í
觨¼.
¡·
>T
AnÍþ´G2[ÇÜE›
!
*1Kôӛ

$
wxØ  Gʂ–#@%
WL(

&
rÇ]nÍþ6„`-¨Úr[E›
ò­[!ãÀÇYZËÒ[)Ç
!
Ç¥E›H|
!
f
Cw虅T[E›

؏Ö!
#
.—>
#
±
#

#

ÑtCO‡rÇê`
!
Aª]
3T1Z3>1
²PQ[ßQÐr
[nÍþl¨Ú…T[E›³|yH}z

]ßQÐ~GÀÁr
!3T1$
wx
.
W
T
W
%
³f‰ŠE›

Ö!Eêßà1K›ÇÏèÿxñõ
!
]
.
W
T
W
PQ[~
GÀÁ³âr
!
Ö!~gÇܸºÑ¶Àsª[
I3>=
¼
k‹)>’<¦ü

Z7
!
§¨Æ.
!
ñ¡R\ÀÁJ
Ú[Y¡R\Ñ*tY[§s\`g…Ö!~²ÇÜ
!
nÍþäã[
3T1
ѱ²¶À`R¨e
WX(

.„l˜Ð;”
$(&(G2%/) 0U) %(0/)$)G(!-13%
ƒ„R
.—>H}èu¡[óž RlñsÑAlñs[E›
!
ª
YìÍnÍþ~3…[
3T1
‹)ªÊ
!
Í±²~
$
Wp
‹
)ª¨
!
>¨j
=@8
Ñ©ª@„À§[ƒ›
W[(

±C!ãrÀÇ]r…6X›1KßQÐM 
!
¬
­wx«:ÑßÊ,N
!
è¬[C
!
±[·•µ#Ìg.
uÇÜ~ϲ¿[£­xy[þi¥x
!
ÊÞªQØ
#
lW
ƒ´Ñ6!ž@
!
>¾,A“¬—[½ ›
!
ª…é[¡
R\E›gÍ58ù•ÑÞ3*t‹)ŒÊÞ
!
ÍÊ
‚–#@\Í4Y4|Ú
WN;W_(

±gÇܓ¬ #
;
±²¶
À
!
ª´ÜiFnÍþ~ÿ©·*t
$4)G/4U&)*U%/2();W!
,8;W%
¼k
!
¥a
=@8
[ãÚè‰
!
±]PQ¡¶Àª„
7G&;W
¼k[Z7
!
ÇÜâ¶Àª„
G$0U$0(;_
[¼k
!

“¬ #
;
±²
!
±µ#Ìѱ~RgÇܱ²ª„PQ
[¶À

f*Ö|›[§¨0•½
!
±µ#Ìѱ~
]¡¶À7²³[¡R\E›‚&C¨e
>T
Ñ
3T1
‡l
ñs[ãÚ
OM;OP(

]nÍþ~
!
Hê—gû°ÇÜHâR\§

Hê—m
/LW^W/
{
OX
ï{
P[
•
WMPP
÷
_
²
!!!!!! ! ! ! ! ! !!!! ! ! ! !
S/&fOX! :004(!P[
1(U2(Ib(%! WMPP
¡¥aƒ@[ãÚ;ÇÜR[á•ÑâÖ؟ÿ

ñ؟
ÿäã[
=@8
[éÿÞ
!
a#ä¥a
=<8Z=@8
[_

è
ƒ„¼.
=<8C$=<8;$G2D$2(5 U%/2() V)$0(!=<8C%
[äƒ
*gCHê—ÇÜnÍþÞg[0•g|

§¨0•¼.
!
ÑQÇÜnÍþÞgè÷“¬—½ ›[µ…
!
`ÑH
ê—g_¨45ØѝYôÓgN
!
ìCªwþ´Üb¶ƒ
„
OW(

wê—C| €_…6X›1KßLQÐM [
ÇÌ
!
§¨Æ.
!
wê—gu¡Ç܅~ÏPQ[
(>T1
¼
k‹)[ÊÞ
!
±f¨e
>T
[ãÚG
3>1
[äã
!
>ÊÞ
Qó58ù•
!
±fkhA¡
W
âØ  Gª²P[ßL
QÐM 
OO(

¨ôÓEŸ¶*¼RêLʂ~C¥¤
!
“L…
Q

AxLrʂÃB[xy
!
]ËvÇ~ÙÖ¥¾gÇÜ

>T
[ãÚ
!
ÊÞ
>T1
[¼k

R]ÏËí–
!
…Qä
JÚnÍþÀÁ
!
]…QÙN
7G&;W
ѱ²{—

[¼kä
¥a
!7$K
[¼k|ÊÞ
!
ìavD\]ËvÇ~ÙÖ¥¾R
gÁ»Ÿ

vÇ~ÙÖ¥¾gͱ²{—

R\§[¡
¼k»Ÿ!
³h,nÍþR\:@\[E›
!
f*
!

~g¨©…Q*Eª[
=@8
‹)
O^(

B:?.@
CŠ”R[| “ʂ–#@\[ª„
!
u
®¯šÑu®¯5šg¨e
B:?.@
PQ[
3T1!:B;N!
H*
±²Á\ª„
$I/)/GA2(G#(I/$2%$G2$)2U%/2();P!<8;P%!
@>J;

!:B;X
[ãÚѼk

f*
!
§¨¼.
!
avE›Cm
¡¨e
3T1
[ãÚÑ
>=R8.
R\§[ƒ›;§R[
OL(

tCOC›1KVº
#
ùúё’[| rÇ
!
¡q
Aª¡R\E›[6„´Üƒ„Y™
!
Rûý
!
胄±@
ƒ„/tCOA
TK;BRB
PQ[~GÞgÑÒ[1K´Ü
!
>R
!
tCOgÇÜ
BRB
[R\>’<¦ü
!
ªgu¡
¨e
TK;BRB
PQäã[
3T1
Ñ~G±²
(>T1
[¼k
!
¨
e
>T
[ãÚ
!
.ÊÞ
3>1
[ãÚ
!
gÊÞÏ3…[ä
6„¼k
!
wx
S=<;P $D$0G4&$%G(&4&$%$5#(0/) I/&(;
G4&(;P!S=<;P%!-;
´µ—
$-;0(&(G2/)%
‡


!
tCO
gÊÞ±²~EŸ3…[
$
Wp
<
!
¨©nÍþ¥.I[)
Ä
!
¨e±²{—

[O~
!
*’<¦ü
OX(


60
vh[ƒ„¼.
!
–([ßQп ª—Riƒ›Rè
‰
!
>*g“³ß¢ÙN~[nÍþÞgÑÒ

nÍþ[
ÞgÑÒiʂ–#@\[ãè‰
!
>*(gm¡ef
“¬—GYôӇª¸iʂ@\è‰[©Åª—
!

|›aµÊ‚@\[×

òfAnÍþƒ„[=Ð
!
±ºR]nÍþ~،]
f| Šâ[
>T1!
…Pê
I2>T1!
ñªäã[
>T
äQ¿n
ÍþsYr[¡RöÍ@KäÌ¡·
!

3>1!
JÚnÍ
þG±²ÀÁ
!
£¾“M 

nÍþ´Üm¡ƒ›R
Z
j
[³U*PQßQб²ÞgÑÒ£¤Q¿Ê‚–#@!
ª.
!
\›¡R\Û
Z
¡Ís\;¨©
3T1Z3>1
­KÎ[·
CA±¨Ê‚–#@\| U2[Ù0Ñ1K…}

՝
rÇE›[™`-¯›
!
ªƒ„3NVx
!
n¤7²G[
j‰rÇ;¦
!
Ö!鋵#ÌÑNšµ#̌èEH[¡
R\E›

ªrNšµ#ÌAAlñs[óžE›£H
!
ª
5C鋵#Ì
!
Z7=F[AlñsóžgNŒ…
SG
[óžgN
O[(

±m¡¡R\gkhA¡Ê›™š[
éON(

wêEH}.uÊÞ-÷•˜›xyQó

!
µ…Qó
1TR
Ñ
?1.;8+
ƒ›
!
>è鵅-÷•˜
›xy[]°ö±gN
O_(

tCO‹µ#Ì*ÊÞ
;IAG

I3>=
¼k‹)
!
±fÇܟV±²¥Z
!
AŸV[|
ÚÑסÙwè|Ô[SÙE›
^M(

ñ.*•
!
rǙ
`-[¯›iª\]Ú_[™#›è‰
!
rÇ]A¡ñ
3T1Z3>1
JÚ[nÍþÞgÑÒGª²“[ßQÐM 
[Z7èª¸E›

f*
!3T1
ääƒ[¶Àm+rè
û.g™[vÀ*t
!
ìrÀÇ]a…T[YA›NEDY
™
!
‚&R®rrÇm¡ef¶Àm+[¡ùúƒ„

û
ÿËa|m+;¨©ôÓÑßQÐÞg[ƒ„ÿe
!
‚&
ȪCrÇ]a…T[E›´ÜY¬./
!
(«B]EÎ4
5
!
ºg=Ѓ„rÇAM [nfm+ef
!
Vgèé
‚a|¯°[ct
!
a»CEF[öƒ²´

$
“”•–
%
P (!<$*5$&()$B%G4! @$V e((=EF3($G2D(/KA*() 0U(G(0! G(&;
&4&$%%(5/K0A02(I0! $)5 $U/U2/009(FJ%((3$5G7/&<(5!
WMPM!^N$X%.[^_F
W (!B((9e! 94)*?e! .(/.9! (2$&F^ ;.A5%/KA)/)()$&)54G(0
D$0G4&$%0I//2# I40G&(G(&$U/U2/002#%/4*# I2/G#/)5%$&*();
(%$2/) /6%($G2D(/KA*() 0U(G(09(F@/KG$&B(2!WMMX!PXX.
WPWF
O (!?()*e9! BbbA8F8%/*%(00/) /6$2#(%/I$.$02%4**&(b(2E(()
5($2# $)5 U%/G%($2/) 9(F=%2(%/0G&(%@#%/Ib S$0G7/&!WMMW!
WW$_%.PO[MF
^ (!3$53! $00)$=! ./5$%$3F>2%G/K5($)5 U(%/KA)2%2();
2(%$G2/)0E2# I2/G#/)5%$9(F97/&#(I!WMMW!ONO$O Z^%.
^MPF
L (!7$&)*(%1 aF<2#/)5%$&5A064)G2/) ) G$%5/D$0G4&$%50($0(
9(FJ%((3$5G7/&<(5! WMML! ON$PM%.PW[NF
X (!<$5$I$)G#>3! 34)*(<1F<2#/)5%$&5A064)G2/) $2#(%/;
0G&(%009(F%G3(0! WMM[!PMM$^%.^XMF
[ (!124IU 1! 1#/%2C3! 7*(&/EI$) 0&(&(2$&I40G&(I2/G#/)5%$&=@8U%/54G2/)!U%/2() 0A)2#(;
00!$)5 I3>=2%$)0G%U209(F8%/G>$2&=G$5 1G,1=! WMMO!
PMM$PO%.[__XF
N (!8(2(%0() CJ! 7(6%/AR! R46/4%1!(2$&F<2/G#/)5%$&5A064)G;
2/) ) 2#((&5(%&A. U/00b&(%/&() )04&) %(002$)G(9(F1G;
()G(! WMMO! OMM$LXWW%.PP^MF
_ (!?$%5)/:! -5(&02() R! 7%/E)&((2/K5$)20U%(D()2#AU(%*&AG(I$;)54G(5 6/%I$2/) /6)2%$G(&4&$%
/XW^W/
{
OX
ï{
P[
•
WMPP
÷
_
²
!!!!!! ! ! ! ! ! !!!! ! ! ! !
S/&fOX! :004(!P[
1(U2(Ib(%! WMPP
$5D$)G(5 *&AG$2/) ()5 U%/54G20) b/D)(()5/2#(&$&G(&09(F9
&) :)D(%2! P__X!_[$X%.P^WWF
PM(!>0#V$E$@! -5(&02() R! R4 +B! (2$&F>/%I$&`)*I2/G#/);
5%$&04U(%/K5(U%/54G2/) b&/GV02#%((U$2#E$A0/6#AU(%*&AG$(;
IG5$I$*(9(F>$24%(! WMMM!^M^$X[[_%.[N[F
PP(!//U(%1 =! a#$&(A;/))(&=! .$bb9!(2$&F3());$)*/2();
0);$&5/02(%/)(0A02(I$)5 /K5$2D(02%(00) G$%5/D$0G4&$%)04;
&) %(002$)G(9(F=I9U#A0/&.($%2%G8#A0/&! WMM[! W_O
$^%..WMM_F
PW(!>0#/e! C$)$`$E$=! >$*$e! (2$&F3(*4&$2/) $)5 %/&(/6
2#(I2/G#/)5%$&2%$)0G%U2/) 6$G2/%) 2#(5$b(2G%$2#($%29(F
=)) >e=G$5 1G! WMM^!PMPP.[NF
PO(!8! C#$&&/D-() A`I(0) G%G4&$2)*&AIU#/GA2(054%)*#(I/0/%U2/) 6/%(KU(%;
I()2$&#AU(%G#/&(02(%/&(I$9(F74&-V0U 7/&<(5! P_NO!_X
$_%.OLF
P^(!C)*#2;B/`$)/=! e/4)*?! 74%/ERB!(2$&F*$%(2(
0I/V((KU/04%($)5 #AU(%G#/&(02(%/&(I$)G%($0(I2/G#/)5%$&
5$I$*() G$%5/D$0G4&$%2004(09(F%G4&$2/)! WMMW! PML
$[%. N^_F
PL(!e$/80/G$2(5 E2# E5(0U%($5 I2/G#/)5%$&5A064)G2/) $)5 $G2D$2/)
/62#(I2/G#/)5%$&$U/U2/00U$2#E$A9(F97/&#(I! WMMP!
W[X$^L%.^W^XNF
PX(!#()*9! 43! #() .!(2$&FTK5`(5 &/E;5()02A&U/U%/;
2() 02I4&$2(0ULO;5(U()5()2$G2D$2/) /6U%/$U/U2/2G7$K&($5;
)*2/$U/U2/00/656(%()2$2(5 ()5/2#(&$&U%/*()2/%G(&09(F
-)5/G%)/&/*A! WMM[!P^N$L%.WMNLF
P[(!J&(I)*:! U%/2() )G%($0(004U(%/K5(U%/54G2/) bA()5/2#(&$&)2%G/K5(
0A)2#$0(bA)#b2)*8C$&U#$9(F$%5/D$0G3(0! WMML!XL
$^%.N_[F
PN(!1#/HI$:!e(6%(I$0#D&U/02)$2$&#($%2*%/E2# ) %(0U/)0(2/)04&) $)5 )42%2/)$&02$240
9(F97/&#(I!WMMW!W[[$^M%.O[X[MF
P_(!b(2(0I(&240.$
P
.;I$*)(2G%(0/)$)G(0U(G2%/0G/UA0245A9(F
%G4&$2/)! WMM[!PPX$PM%.PP[MF
WM(!CI9=! 0#U0b(2E(() )04&) %(002$)G($)5 ()5/2#(&$&5A064)G2/).I/;
&(G4&$%$)5 U$2#/U#A0/&/*G$&I(G#$)0I09(F%G4&$2/)!
WMMX!PPO$PL%.PNNNF
WP(!R$D50/) 1 2)*2/D$0G4&$%64)G2/) $)5 50($0(9(F%G3(0! WMM[! PMM
$N%.PPWNF
WW(!-52# B4b/0! R$)(-.$)5A! 9/0(U# B/0G$&`/F3/&(/6/K5$2D(
02%(00$)5 )2%G/K5() $2#(%/2#%/Ib/009(FJ%/)27/0G!
WMMN! PO.LOWOF
WO(!B$G`$c! 840V$%5(0A)2#$0(0G/)02242D(&A$G2D($)5 064)G2/)$&A4U%(*4&$2(5
) #AU/K$9(FJ%((3$5G7/&<(5! WMMP!OP$PW%.PXM_F
W^(!?#$6/4%6$%8! $5()$0-F<2/G#/)5%$&)2%G/K5(0A)2#$0(
9(F@%()508#$%I$G/&1G! WMML! WX$^%.P_MF
WL(!8/5(%/0/99F@#(6/%I$2/) /6U(%/KA)2%2() 2#($UU&(5 U#A0;
/&/*A/6I2/G#/)5%$&)2%G/K5(9(F=%G# 7/G#(I7/U#A0!
WMM_! ^N^$W%.WP^F
WX(!d$) 9! 9$)*J! a$)*7!(2$&FTU#/U/*/)) RU%(D()20.
W
T
W
;
)54G(5 )H4%A) U%I$%A#4I$) 4Ib&G$&D() ()5/2#(&$&G(&0
9(F-2#)/U#$%I$G/&!WMPM!PWN$W%.^ONF
W[(!c#$)*3! C$)*C=! 8$/<9!(2$&F742) %(54G(0/K5$2D(
02%(00;)54G(5 I2/G#/)5%$&5A064)G2/) D$0G$D()*)*/6%($G2D(
/KA*() 0U(G(09(FJ//5 #(I@/KG/&! WMPM! ^N$O%._WWF
WN(!e4) 1 >!0(2/6#*#;6$25(2)54G(5 #AU(%*&AG(I$$)5 /b(02A) :3IG(
9(F=%G# 8#$%I3(0! WMM^!W[$[%.[_MF
W_(!CI1 .!8$%V C1F-6(G20/6#$#%($)*$ (K2%$G2/) &U5 I(;
2$b/&0I) #4I$)09(F8#$%I$G/&3(0! WMMO!^N$L%.LPPF
OM(!B4/9c! B4/BF=I(%G$) *)0()*02I4&$2(0)04&) U%/54G2/)
$)5 U%(D()20$U/U2/002#%/4*# %(*4&$2/) /64)G/4U&)*U%/2();W
) G4&24%(5 b(2$G(&09(F-D5 7$0(5 /IU&(I()2=&2(%)$2<(5!
WMMX!O$O%.OXLF
OP(!CI.e! CICF8%/2(G2D((6(G2/6*)0()*/) GA2/V)(;);
54G(5 $U/U2/00) U$)G%($2Gb(2$;G(&09(F9=*%GJ//5 #(I!
WMM[!LL$N%.WNPXF
OW(!e) 9! ?$/c! B4 R! (2$&F7(%b(%)(IU%/D(0*&4G/0(I(2$b/;
&0I2#%/4*# )54G2/) /6*&AG/&A009(F=I98#A0/&-)5/G%)/&
<(2$b!WMMN!W_^$P%.-P^NF
OO(!e$) B8! #$) 1 a! #$) =1!(2$&F84(%$%) 5(G%($0(00(%4I
2/2$&G#/&(02(%/&$)5 ()#$)G(02#/%$GG$/%2$()5/2#(&$&)2%G/K;
5(0A)2#$0((KU%(00/) ) 5(2;)54G(5 #AU(%G#/&(02(%/&(IG%$20
9(FB6(1G! WMMX! [_$^%.OW^F
O^(!R/)*<(#()!B$)*+$/!+) $!(2$&F:)D/&D(I()2/6I4&2;
2$%*(20) U$(/)6&/%);)54G(5 U%(G/)52/))*9(F98#$%I$G/&
-KU @#(%!WMMX!OP_$P%.PXLF
OL(!.(/1 C! e4) .9! e.1! (2$&F-D/5$I)($)5 %42$(G$%U)(
)#b2I*%$2/) bAB:?.@D$04UU%(00/) /6>=R8./K5$0($G;
2D$2/)9(F9(&7/G#(I! WMM_! PM[$P%.PWOF
OX(!C4/aa!.4$)*e!#4)*9?!(2$&F%45((K2%$G20/61/&$;
)4I&A%$24IU%/2(G2()5/2#(&$&G(&0$*$)02/K5`(5 &/E;5()02A
&U/U%/2();)54G(5 )H4%AbA5%(G2$)2/K5$)2$G2/)9(FS$0G
14%A! WMM_!LM$^%.N^_F
O[(!
â³H
F
Ö!µ#Ì[¡R\ƒ›ÑÇ9(F
Ï
iŸN¯
!WMM[!OO$_%.L[F
ON(!
Æl.
!
îÎú
!
v´
F
±~
3*
P
¡R\gN[§¨ƒ
„
9(F
1)rÀ]A]1
! WMM_!WP$P%. OXF
O_(!
µØ¶
!
·Dr
!
Á¸ú
!
‡
F
wêµ#Ì¡R\ƒ›ƒ„
9(F
(€ð¯ö]
! WMMN!OX$W^%.PMLMNF
^M(!
º½½
!
Á¹
!
̈́Y
!
‡
F
tCOµ#ÌAŸV
1<<;[[WP
±²¥ZG
;IAG
sª¼k[ÇÜE›
9(F
6úÀ]
!
WMMX!W[$PW%. PP[_F
/[W^W/
{
OX
ï{
P[
•
WMPP
÷
_
²
!!!!!! ! ! ! ! ! !!!! ! ! ! !
S/&fOX! :004(!P[
1(U2(Ib(%! WMPP
>0DBVEBCHG0/1HFKMICVD0BC0CHIVAHOF AQVAKK0SA:8=R:5=-.AD/OB10V
V/GH0BS/KVI1/GH0KA/KA/CHDG/H0D0BC/12E0CAKA.AH0V0CAK0CDAGSACD0BC
c.=>?#()G#()
P
! B:,94)
P
! 8=>.4H4)
P
! e=>?+$/&4
P
! 7:=>C$
P!W
!
$PO;/0#1 E*)*#027 :$)!(!/!*4&0;&1*0$(L*1 ?7($*)*;*1(2($*! =7#$7#(A$(B*0)(!8&4@0#1(!(&$#-
?7($*)*;*1(2($*! =7#$7#(WMPWMO! ?7($#&
WOP*6#0!.*$!&4:$!*0#!(B*F(&-&8#$1 7#0.#2&-&8! :$)!(!/!*&4;&-*2/-#0;*1(2($*!A$(B*0)(!8&4
@*%#);*1(2#-=27&&-! N&/)!&$! @D[[MOM! A=5%
6OKDG/VD(!<(2$b/&GG$%5/D$0G4&$%50($0(0$2AU(/650($0(E#G# $&I/02G$40(5 bAb/5AG$%b/#A5%$2($)5 &U5 I(2$b/;
&0I5A064)G2/)F@AU(W 5$b(2(0I(&2400$2AUG$&I(2$b/&G50($0(F:2)/2/)&A&($5 2/2#()04&) %(002$)G(b42$&0/%(&$2(5 2/
$2#(%/0G&(%/00FTK5$2D(02%(000U%/54G(5 bA2#(%($G2D(/KA*()Z)2%/*() 0U(G(0$3T1Z3>1% FTK5$2D(02%(00$)5 20G/)0(;
]4()G((D()20U&$AIU/%2$)2%/&(0) $2#(%/0G&(%/00$=1%F<2/G#/)5%$$%(b/2# 0/4%G(0$)5 2$%*(20/6%($G2D(/KA*() $)5Z/%)2%/;
*() 0U(G(0$3T1Z3>1%! $)5 2#(%(0*%/E)*(D5()G(2#$2I2/G#/)5%$&5A064)G2/) I$Ab(%(&(D$)2)2(%I(5$2(I(G#$)0IbA
E#G# G$%5/D$0G4&$%%0V 6$G2/%0&($5 2/2#(6/%I$2/) /6D$0G4&$%&(0/)0F1(D(%$&G$%5/D$0G4&$%%0V 6$G2/%0$%(5(I/)02%$2(5 G$40(0/6
I2/G#/)5%$&5$I$*(F@#0%(D(E02$%20E2# (KG(00D(3T1Z3>1;)54G(5 I2/G#/)5%$&5A064)G2/)F@#($42#/%0(IU#$0`(2#(%(&$;
2/)0#U $I/)*$K0/6(KG(00D(3T1Z3>1;I2/G#/)5%$&5A064)G2/);$U/U2/00;$2#(%/0G&(%/00F@#(A$&0/)2%/54G(0(D(%$&2%$52/)$&
#)(0(I(5G)(004G# $0367(&6&&$ M#6&$(2/)! b42)! #$#%($)*$! /*0#0(# -&H#!#! =&-#$/.-80#!/.$)5 0//) ) 2#(2%($2I()2
/6%(&(D$)250($0(02#%/4*# $)2;3T1Z3>1 I(G#$)0IFG$&2A/6@<056(%()26%/I2#(0)*&((6(G2/6G&$00G$&E(02(%) I(5G)(0F
_AF YBGHK(!%($G2D(/KA*() 0U(G(0& %($G2D()2%/*() 0U(G(0& I2/G#/)5%$&5A064)G2/)& $U/U2/00U$2#E$A& $2#(%/0G&(%/00
HB0.!+ %`#)RV[V..#+!!!(#&
$
—˜$Q
!
£¤¤
%
/NW^W/
{
OX
ï{
P[
•
WMPP
÷
_
²
!!!!!! ! ! ! ! ! !!!! ! ! ! !
S/&fOX! :004(!P[
1(U2(Ib(%! WMPP