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Jin-Lian
Chen, Wei-Xiong Chen, Jin-Shui Zhu, Ni-Wei Chen, Department of
Gastroenterology, Shanghai Sixth People's Hospital, Shanghai Jiao-Tong
University, Shanghai 200233, China
Tong Zhou, Department of Nephrology, Ruijin Hospital, Shanghai
Second Medical University, Shanghai 200025, China
Ming-Jun Zhang, Animal Laboratory, Ruijin Hospital, Shanghai Second
Medical University, Shanghai 200025, China
Yun-Lin Wu, Department of Gastroenterology, Ruijin Hospital,
Shanghai Second Medical University, Shanghai 200025, China
Supported by the National Natural Science Foundation of China
(No.39970340) and the Scientific Foundation of Ministry of Public
Health
Correspondence to: Jin-Lian Chen, Department of
Gastroenterology, Shanghai Sixth People's Hospital, Shanghai Jiao-Tong
University, Shanghai 200233, China. cqinqin@fm365.com
Telephone: +86-21-64369181
Received: 2002-12-30
Accepted: 2003-02-19
Abstract
AIM: To investigate the effect of tetramethylpyrazine on
hepatic/renal ischemia and reperfusion injury in rats.
METHODS:
Hepatic/renal function, histopathological changes, and hepatic/renal
P-selectin expression were studied with biochemical measurement and
immunohistochemistry in hepatic/renal ischemia and reperfusion
injury in rat models.
RESULTS:
Hepatic/renal insufficiency and histopathological damage were much
less in the tetramethylpyrazine-treated group than those in the
saline-treated groups. Hepatic/renal P-selectin expression was down
regulated in the tetramethylpyrazine-treated group.
CONCLUSION:
P-selectin might mediate neutrophil infiltration and contribute to
hepatic/renal ischemia and reperfusion injury. Tetramethylpyrazine
might prevent hepatic/renal
damage induced by ischemia and reperfusion injury through inhibition
of P-selectin.
Chen
JL, Zhou T, Chen WX, Zhu JS, Chen NW, Zhang MJ, Wu YL. Effect of
tetramethylpyrazine on P-selectin and hepatic/renal ischemia and
reperfusion injury in rats. World J Gastroenterol
2003; 9(7): 1563-1566
http://www.wjgnet.com/1007-9327/9/1563.asp
INTRODUCTION
Hepatic/renal ischemia-reperfusion injury is common clinically.
Up to now, there has been no effective treatment for this
pathological injury. Cell adhesion molecules have been found to play
an important role in hepatic/renal ischemia-reperfusion injury by
mediating interactions of polymorphonuclear neutrophils with
endothelium. P-seletin monoclonal antibody has been demonstrated to
prevent effectively reperfusion-induced hepatic/renal tissue damage[1-23].
Tetramethylpyrazine (TMP), a traditional Chinese herb, has been
widely used especially in the treatment of patients with cerebral
and cardiac ischemic diseases in China. Experimental study has found
that TMP could protect vascular endothelial cells, and inhibit
respiratory explosion and free radicals of polymorphonuclear
neutrophils[24-28]. In the present study, we investigated
the effect of TMP and P-selectin on hepatic ischemia and reperfusion
injury in rats.
MATERIALS
AND METHODS
Animal model
Ninety male Wistar rats (Shanghai Experimental Animal Center
of Chinese Academy of Sciences), weighing 200±10 g, were given free
access to food and water for three days before the experiments. The
rats were anesthetized with 2.5 % sodium pentobarbital
intraperitoneally, and randomly divided into 2 groups. In one group
of rats, the ligament linking liver, diaphragm and abdominal wall
were separated, the portal vein and liver artery that drain blood to
left hepatic lobe were freed by blunt dissection and then blocked
with a microvascular clamp for 60 minutes, then the clamp was
removed, and reperfusion was performed. While in the other group,
the left renal artery was freed, and blocked with a microvascular
clamp for 60 minutes, then the clamp was removed and reperfusion was
performed, simultaneously, the right kidney was cut off. The two
groups of rats were randomly divided into TMP-treated group (n=20)
and non-treated group (n=20). They were divided into
subgroups according to the indicated time 1,3,6,24 hours after
reperfusion. TMP or saline was intravenously injected five minutes
before the reperfusion. A sham-operated group (n=5,
anesthesia and opening celiac cavity, no blocking of hepatic or
renal blood flow) served as control.
Collection
and measurement methods of specimens
Blood and hepatic and renal tissues were harvested at the
indicated time. Serum levels of aspartate aminotransferase (AST) and
alanine aminotransferase (ALT), and blood urea nitrogen (BUN) and
creatinine (Cr) were measured with a 747 automatic analyzor (Hitachi
Boehringer Mannhein, Mannhein, Germany). Hepatic and renal tissue
samples were fixed in 10 % formalin and embedded in paraffin. 5 mm
thick sections were cut into and stained with hematoxylin and eosin
for light microscope examination. Expression of P-selectin in
hepatic/renal tissue was detected by immunohistochemistry method
with a labeled streptavidin biotin (LSAB) kit (Fujian Maixin
Biotechnology Co., products of Biotechnology Co. CA, USA).
Statistical
analysis
Data were presented as
 ,
and Student's t test was used to determine changes between different
groups. P<0.05 was considered significant.
RESULTS
Histopathologic evaluation
One hour after reperfusion, visual observation revealed that
the left hepatic lobe was more swollen than the right lobe, and was
dark in color. Under the light microscope, interstitial congestion
and infiltration of inflammatory cells were observed. One hour after
reperfusion, the renal cortex was macroscopically pale, the renal
medulla displayed blood stagnation and was dark in color. Under the
light microscope, edema, denaturation with different extent and
necrosis of renal tubular epithelial cells were observed.
Simultaneously, interstitial congestion, edema and infiltration of
inflammatory cells were also observed. However, in the TMP-treated
group, the outward appearance of the liver and kidney was similar to
that of normal. Hepatic cells and tubular cells showed less swelling
and no denaturation or necrosis, and interstitial changes were not
obvious.
Hepatic
and renal function evaluation
Twenty four hours after hepatic reperfusion, the serum
levels of ALT (628±91 u/L) and AST (1 608±199 u/L) in the
saline-treated group were much higher than those in the
sham-operated group (52±11 u/L and 80±17 u/L respectively, P<0.01).
The TMP-treated group revealed significantly lower levels of ALT
(190±21 u/L) and AST (386±62 u/L) than those in the saline-treated
group (P<0.01).
Twenty
four hours after renal reperfusion, the serum levels of BUN (14.54±0.67
mmol/L) and Cr (102.2±4.67 mmol/L)
were much higher in the TMP-treated group than those in the
sham-operated group (7.88±0.57 mmol/L and 39.00±4.47 mmol/L,
respectively, P<0.01). The TMP-treated group presented
with significantly lower levels of BUN (11.21±0.56 mmol/L) and Cr
(70.61±4.95 mmol/L)
than those in the saline-treated group (P<0.01).
P-selectin
expression in hepatic and renal tissues
P-selectin was expressed widely within hepatic and renal
tissues 1 hour after reperfusion, which was mainly distributed on
small vessels of left hepatic lobe and kidney. In addition, it was
also expressed on part of hepatic cellular membrane,
glomerulomesangium, capillary loops, and interstitium. After
treatment with TMP, there were no obvious yellow-brown positive
granules in the hepatic and renal tissues, suggesting that P-selectin
expression was not displayed.
DISCUSSION
Recently, the role of cell adhesion molecules and neutrophils in
ischemia and reperfusion injury has aroused attention[29-50].
Ischemia reperfusion liver injury is characterized by microvascular
leukocyte accumulation and massive infiltration of postischemic
tissues. Primary leukocyte endothelial cell interaction(rolling) is
mediated by selectins, whereas firm adherence and transendothelial
migration involve immunoglobulin superfamily(intercellular adhesion
molecule-1, ICAM-1) with leukocyte b2-integrins
(CD11/CD18)[51]. As a potential member of the selectin
family, P-selectin has been found in both Weibel-Palade body of
epithelial cells of middle and small blood vessels and a-granule
of platelets. It is expressed rapidly on the surface of these cells
in seconds after their activation. Furthermore, P-selectin can be
up-regulated by de novo synthesis in the ischemia-reperfusion injury
in hours. P-selectin plays an important role in inflammation by
initiating neutrophil rolling, adhesion and recruitment to injured
tissue[15]. Blockade of P-selectin expression or
interaction with its ligands can attenuate leukocyte adherence and
infiltration during ischemia and reperfusion injury. And P-selectin
monoclonal antibody has been found to have protective effects on the
injury[21].
Tetramethylpyrazine
(TMP) is an active ingredient of Ligustium Wallich Franch. It has
been shown in animal models and clinical investigations that TMP is
effective on ischemic diseases such as heart, brain and lung. TMP
could block the calcium channel, reduce the bioactivity of platelets
and platelet aggregation, and inhibit free radicals, and has
inhibitory roles in platelets and arterial thrombus formation in
dogs[52]. However, the roles and mechanisms of TMP in
treatment of digestive diseases have not been extensively studied.
The
effect of TMP on ischemia and reperfusion injury was observed in
this study based on the established rat model of hepatic/renal
ischemia-reperfusion.
Hepatic and
renal tissues displayed significantly histopathologic damages after
hepatic/renal ischemia-reperfusion while the serum levels of ALT and
AST as well as BUN and Cr were increased. It was showed that
hepatic/renal injury induced by ischemia-reperfusion was remarkably
attenuated when TMP was given 5 minutes before reperfusion as shown
by improved hepatic/renal function and less pathologic damage. The
results suggest that TMP has a protective effect on hepatic/renal
reperfusion injury by inhibiting the interaction of neutrophils and
endothelium.
After
ischemia and reperfusion, P-selectin expression was up-regulated in
hepatic and renal tissues, suggesting that P-selectin is related to
hepatic/renal reperfusion injury. It was found that leukocyte
rolling and recruitment were delayed when deficient mice are
infected, suggesting that P-selectin is involved in the early events
of inflammation mediated by leukocytes[53]. Results from
this study showed that P-selectin expression in hepatic and renal
tissues was inhibited in TMP-treated group. This is consistent with
down-regulated expression of sialyl Lewis X, a ligand for P-selectin
located mainly in neutrophils, as with anti-P-selectin therapy
(unpublished data). These suggest that P-selectin might mediate
neutrophil infiltration within the liver and kidney in the early
stage of hepatic/renal reperfusion injury. Furthermore, blockade of
P-selectin can attenuate inflammatory cell infiltration and
pathological damage. Wu found that TMP could reduce significantly
the number of a-granule
membrane protein(GMP140) of platelets and had inhibitory effects on
platelets and arterial thrombus formation in dogs. TMP can play a
protective role in hepatic and renal injury caused by
ischemia-reperfusion by inhibiting the adhesion and activation of
neutrophils mediated by P-selectin.
In
an animal model of thioacetamide (TAA) induced acute hepatotoxicity,
increase of serum SGOT and SGPT produced by TAA was decreased by TMP,
and increase of malondialdehyde (MDA) produced by TAA was also
prevented by in vitro addition of TMP to liver homogenates. A rise
of serum interleukin-2 was similarly prevented. The results suggest
that part of hepatocellular injury induced by TAA is mediated by
oxidative stress caused by the action of cytokines through lipid
peroxidation, TMP may act by preventing lipid peroxidation[54].
Another study showed that the hepatoprotective effect of TMP might
be in part due to its inhibitory ability on membrane lipid
peroxidation and free radical formation and its free radical
scavenging ability[55]. Therefore, TMP might be effective
on the treatment of on reperfusion injury.
REFERENCES
1
Funaki H, Shimizu K, Harada S, Tsuyama H, Fushida S, Tani T,
Miwa K. Essential role for nuclear factor kappaB
in ischemic preconditioning for
ischemia-reperfusion injury of the mouse liver.Transplantation 2002;
74: 551-556
2
Khandoga A, Biberthaler P, Enders G, Axmann S, Hutter J,
Messmer K, Krombach F. Platelet adhesion mediated
by fibrinogen-intercelllular adhesion
molecule-1 binding induces tissue injury in the postischemic
liver
in vivo.Transplantation 2002;
74:681-688
3
Satoh S, Suzuki A, Asari Y, Sato M, Kojima N, Sato T,
Tsuchiya N, Sato K, Senoo H, Kato T. Glomerular endoth
elium exhibits enhanced expression of
costimulatory adhesion molecules, CD80 and CD86, by warm ischemia/rep
erfusion injury in rats. Lab Invest
2002; 82: 1209-1217
4
de Rossi LW, Horn NA, Buhre W, Gass F, Hutschenreuter G,
Rossaint R. The effect of isoflurane on neutrophil selectin
and beta(2)-integrin activation in
vitro. Anesth Analg 2002; 95: 583-587
5
Burne MJ, Rabb H. Pathophysiological contributions of
fucosyltransferases in renal ischemia reperfusion injury. J
Immunol 2002; 169: 2648-2652
6
Faure JP, Hauet T, Han Z, Goujon JM, Petit I, Mauco G, Eugene
M, Carretier M, Papadopoulos V. Polyethylene
glycol reduces early and long-term
cold ischemia-reperfusion and renal medulla injury. J Pharmacol Exp
Ther
2002; 302: 861-870
7
Khandoga A, Enders G, Biberthaler P, Krombach F. Poly(ADP-ribose)
polymerase triggers the microvascular
mechanisms of hepatic
ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol
2002; 283: G553-560
8
Horie Y, Yamagishi Y, Kato S, Kajihara M, Tamai H, Granger DN,
Ishii H. Role of ICAM-1 in chronic ethanol
consumption-enhanced liver injury
after gut ischemia-reperfusion in rats. Am J Physiol Gastrointest
Liver Physiol
2002; 283: G537-543
9
Olanders K, Sun Z, Borjesson A, Dib M, Andersson E, Lasson A,
Ohlsson T, Andersson R. The effect of intestinal
ischemia and reperfusion injury on
ICAM-1 expression, endothelial barrier function, neutrophil tissue
influx, and
protease inhibitor levels in rats.
Shock 2002; 18: 86-92
10
Kubes P, Payne D, Woodman RC. Molecular mechanisms of
leukocyte recruitment in postischemic liver microcircu
lation. Am J Physiol Gastrointest
Liver Physiol 2002; 283: G139-147
11
Leonard MO, Hannan K, Burne MJ, Lappin DW, Doran P, Coleman
P, Stenson C, Taylor CT, Daniels F, Godson C,
Petasis NA, Rabb H, Brady HR.
15-Epi-16-(para-fluorophenoxy)-lipoxin A(4)-methyl ester, a
synthetic analogue of
15-epi-lipoxin A(4), is protective in
experimental ischemic acute renal failure. J Am Soc Nephrol 2002;
13: 1657-1662
12
Farmer DG, Amersi F, Shen XD, Gao F, Anselmo D, Ma J, Dry S,
McDiarmid SV, Shaw G, Busuttil RW, Kupiec-Weglinski
J. Improved survival through the
reduction of ischemia-reperfusion injury after rat intestinal
transplantation using
selective P-selectin blockade with P-selectin
glycoprotein ligand-Ig. Transplant Proc 2002; 34: 985
13
Oktar BK, Gulpinar MA, Bozkurt A, Ghandour S, Cetinel S,
Moini H, Yegen BC, Bilsel S, Granger DN, Kurtel H.
Endothelin receptor blockers reduce
I/R-induced intestinal mucosal injury: role of blood flow. Am J
Physiol
Gastrointest Liver Physiol 2002; 282:
G647-655
14
Kuzu MA, Koksoy C, Kuzu I, Gurhan I, Ergun H, Demirpence E.
Role of integrins and intracellular adhesion molecule-1
in lung injury after intestinal
ischemia-reperfusion. Am J Surg 2002; 183:70-74
15
Zhou T, Li X, Wu P, Zhang D, Zhang M, Chen N, Dong D. Effect
of anti-P-selectin monoclonal antibody on
renal ischemia/reperfusion injury in
rats. Chin Med J 2000; 113: 790-793
16
Stepkowski SM, Chen W, Bennett CF, Condon TP, Stecker K, Tian
L, Kahan BD. Phosphorothioate/methoxyethyl-
modified ICAM-1 antisense
oligonucleotides improves prevention of ischemic/reperfusion injury.
Transplant Proc
2001; 33: 3705-3706
17
Deng J, Kohda Y, Chiao H, Wang Y, Hu X, Hewitt SM, Miyaji T,
McLeroy P, Nibhanupudy
B, Li S, Star RA. Interleukin-
10 inhibits ischemic and cisplatin-induced
acute renal injury. Kidney Int 2001; 60: 2118-2128
18
Redlin M, Werner J, Habazettl H, Griethe W, Kuppe H, Pries
AR. Cariporide (HOE 642) attenuates leukocyte activation
in ischemia and reperfusion. Anesth
Analg 2001; 93: 1472-1479
19
Salter JW, Krieglstein CF, Issekutz AC, Granger DN. Platelets
modulate ischemia/reperfusion-induced
leukocyte recruitment in the
mesenteric circulation. Am J Physiol Gastrointest Liver Physiol
2001; 281: G1432-1439
20
Lindner JR, Song J, Christiansen J, Klibanov AL, Xu F, Ley K.
Ultrasound assessment of inflammation and renal tissue
injury with microbubbles targeted to
P-selectin. Circulation 2001; 104: 2107-2112
21
Wu P, Li X, Zhou T, Zhang MJ, Chen JL, Wang WM, Chen N, Dong
DC. Role of P-selectin and anti-P-selectin
monoclonal antibody in apoptosis
during hepatic/renal ischemia reperfusion injury. World J
Gastoenterol
2000; 6: 244-247
22
Kojima N, Sato M, Suzuki A, Sato T, Satoh S, Kato T, Senoo H.
Enhanced expression of B7-1, B7-2, and
intercellular adhesion molecule 1 in
sinusoidal endothelial cells by warm ischemia/reperfusion injury in
rat
liver. Hepatology 2001; 34: 751-757
23
Weigand MA, Plachky J, Thies JC, Spies-Martin D, Otto G,
Martin E, Bardenheuer HJ. N-acetylcysteine attenuates
the increase in alpha-glutathione S-transferase
and circulating ICAM-1 and VCAM-1 after reperfusion in
humans undergoing liver
transplantation. Transplantation 2001; 72: 694-698
24
Huang X, Ren P, Wen AD, Wang LL, Zhang L, Gao F.
Pharmacokinetics of traditional Chinese syndrome and recipe:
a hypothesis and its verification
(I). World J Gastroenterol 2000; 6: 384-391
25
Zhou S, Shao W, Zhang W. Clinical study of Astragalus
injection plus ligustrazine in protecting myocardial
ischemia reperfusion injury.Zhongguo
Zhongxiyi Jiehe Zazhi 2000; 20: 504-507
26
Liu CF, Lin CC, Ng LT, Lin SC. Protection by
tetramethylpyrazine in acute absolute ethanol-induced gastric
lesions.
J Biomed Sci 2002; 9: 395-400
27
Liu CF, Lin MH, Lin CC, Chang HW, Lin SC. Protective effect
of tetramethylpyrazine on absolute ethanol-induced
renal toxicity in mice. J Biomed Sci
2002; 9: 299-302
28
Li M, Handa S, Ikeda Y, Goto S. Specific inhibiting
characteristics of tetramethylpyrazine, one of the active
ingredients
of the Chinese herbal medicine 'Chuanxiong,'
on platelet thrombus formation under high shear rates. Thromb Res
2001; 104: 15-28
29
Dragun D, Hoff U, Park JK, Qun Y, Schneider W, Luft FC,
Haller H. Prolonged cold preservation augments vascular
injury independent of renal
transplant immunogenicity and function. Kidney Int 2001; 60:
1173-1181
30
Young CS, Palma JM, Mosher BD, Harkema J, Naylor DF, Dean RE,
Crockett E. Hepatic ischemia/reperfusion injury
in P-selectin and intercellular
adhesion molecule-1 double-mutant mice. Am Surg 2001; 67: 737-744
31
Yabe Y, Kobayashi N, Nishihashi T, Takahashi R, Nishikawa M,
Takakura Y, Hashida M. Prevention of neutrophil-
mediated hepatic ischemia/reperfusion
injury by superoxide dismutase and catalase derivatives. J Pharmacol
Exp
Ther 2001; 298: 894-899
32
Maroszynska I, Fiedor P. Leukocytes and endothelium
interaction as rate limiting step in the inflammatory response
and a key factor in the
ischemia-reperfusion injury. Ann Transplant 2000; 5: 5-11
33
Laskowski I, Pratschke J, Wilhelm MJ, Gasser M, Tilney NL.
Molecular and cellular events associated
with ischemia/reperfusion injury. Ann
Transplant 2000; 5: 29-35
34 Burne MJ, Elghandour
A, Haq M, Saba SR, Norman J, Condon T, Bennett F, Rabb H. IL-1 and
TNF independent
pathways mediate ICAM-1/VCAM-1
up-regulation in ischemia reperfusion injury. J Leukoc Biol 2001;
70: 192-198
35 Fuller TF, Sattler B,
Binder L, Vetterlein F, Ringe B, Lorf T. Reduction of severe
ischemia reperfusion injury in rat
kidney grafts by a soluble P-selectin
glycoprotein ligand. Transplantation 2001; 72: 216-222
36 Oe S, Hiros T, Fujii
H, Yasuchika K, Nishio T, Limuro Y, Morimoto T, Nagao M, Yamaoka Y.
Continuous intravenous
infusion of deleted form of
hepatocyte growth factor attenuates hepatic ischemia-reperfusion
injury in rats. J
Hepatol 2001; 34: 832-839
37 Kobayashi A, Imamura
H, Isobe M, Matsuyama Y, Soeda J, Matsunaga K, Kawasaki S. Mac-1
(CD11b/CD18)
and intercellular adhesion molecule-1
in ischemia-reperfusion injury of rat liver. Am J Physiol
Gastrointest Liver
Physiol 2001; 281: G577-585
38
Cabrera PV, Blanco G, Argibay P, Hajos SE. Isoforms
modulation of CD44 adhesion molecule in a murine model
of ischemia and intestinal
reperfusion. Medicina 2000; 60: 940-946
39 Serracino-Inglott F,
Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg
2001; 181: 160-166
40 Taut FJ, Schmidt H,
Zapletal CM, Thies JC, Grube C, Motsch J, Klar E, Martin E. N-acetylcysteine
induces shedding
of selectins from liver and intestine
during orthotopic liver transplantation. Clin Exp Immunol 2001; 124:
337-341
41 Bojakowski K,
Abramczyk P, Bojakowska M, Zwolinska A, Przybylski J, Gaciong Z.
Fucoidan improves the renal blood
flow in the early stage of renal
ischemia/reperfusion injury in the rat. J Physiol Pharmacol 2001;
52: 137-143
42 Opal SM, Sypek JP,
Keith JC Jr, Schaub RG, Palardy JE, Parejo NA. Evaluation of the
safety of recombinant P-
selectin glycoprotein
ligand-immunoglobulin G fusion protein in experimental models of
localized and systemic
infection. Shock 2001; 15: 285-290
43
Zingarelli B, Yang Z,
Hake PW, Denenberg A, Wong HR. Absence of endogenous interleukin 10
enhances early
stress response during post-ischaemic
injury in mice intestine. Gut 2001; 48: 610-622
44 Rivera-Chavez FA,
Toledo-Pereyra LH, Martinez-Mier G, Nora DT, Harkema J, Bachulis BL,
Dean RE. L-selectin
blockade and liver function in rats
after uncontrolled hemorrhagic shock. J Invest Surg 2001; 14: 7-12
45 Chen W, Bennett CF,
Condon TP, Stecker K, Tian L, Kahan BD, Stepkowski SM. Methoxyethyl
modification
of phosphorothioate ICAM-1 antisense
oligonucleotides improves prevention of ischemic/reperfusion injury.
Transplant Proc 2001; 33: 854
46
Ghobrial R, Amersi F, Stecker K, Kato H, Melinek J, Singer J,
Mhoyan A, Busuttil RW, Kupiec-Weglinski JW, Stepkowski
SM. Amelioration of hepatic ischemia/reperfusion
injury with intercellular adhesion molecule-1 antisense
oligodeoxynucleotides. Transplant
Proc 2001; 33: 538
47
Koksoy C, Kuzu MA,
Kuzu I, Ergun H, Gurhan I. Role of tumour necrosis factor in lung
injury caused by
intestinal ischaemia-reperfusion. Br
J Surg 2001; 88: 464-468
48 Sun Z, Wang X, Lasson
A, Bojesson A, Annborn M, Andersson R. Effects of inhibition of PAF,
ICAM-1 and PECAM-1
on gut barrier failure caused by
intestinal ischemia and reperfusion. Scand J Gastroenterol 2001; 36:
55-65
49 Amersi F,
Dulkanchainun T, Nelson SK, Farmer DG, Kato H, Zaky J, Melinek J,
Shaw GD, Kupiec-Weglinski JW, Horwitz
LD,Horwitz MA, Busuttil RW. A novel
iron chelator in combination with a P-selectin antagonist prevents
ischemia/reperfusion injury in a rat
liver model. Transplantation 2001; 71: 112-118
50 Wada K, Montalto MC,
Stahl GL. Inhibition of complement C5 reduces local and remote organ
injury after intestinal
ischemia/reperfusion in the rat.
Gastroenterology 2001; 120: 126-133
51 Chen JL, Zhou T, Chu
YD, Xu HM, Li X, Zhang MJ, Zhang DH, Wu YL. Study on intercellular
adhesion-1 and P-selectin
in liver ischemia and reperfusion
injury. J SSMU 1998; 10: 63-65
52 Zou LY, Hao XM, Zhang
GQ, Zhang M, Guo JH, Liu TF. Effect of tetramethyl pyrazine on
L-type calcium channel in
rat ventricular myocytes. Can J
Physiol Pharmacol 2001; 79: 621-626
53
Frenette PS, Mayadas
TN, Rayburn H, Hynes RO, Wagner DD. Susceptibility to infection and
altered hematopoiesis in
mice deficient in both P-and E-selectins.
Cell 1996; 84: 563-574
54 So EC, Wong KL, Huang
TC, Tasi SC, Liu CF. Tetramethylpyrazine protects mice against
thioacetamide-induced
acute hepatotoxicity. J Biomed Sci
2002; 9: 410-414
55 Liu CF, Lin CC, Ng LT,
Lin SC. Hepatoprotective and therapeutic effects of
tetramethylpyrazine on acute econazole-
induced liver injury. Planta Med
2002; 68: 510-514
Edited
by Xu
XQ and Wang XL
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PubMed