Role of nitric oxide in Toll-like receptor 2 and 4 mRNA expression in liver of acute hemorrhagic necrotizing pancreatitis rats.
OBJECTIVE
To investigate the role of nitric oxide (NO) in Toll-like receptor 2 (TLR2)/4mRNA expression in livers of acute hemorrhagic necrotizing pancreatitis (AHNP) rats.


METHODS
One hundred and ten SD male rats were randomly divided into sham-operated group (n=10), AHNP group (n=30), chloroquine (CQ)-treated group (n=30) and L-Arg-treated group (n=40). TLR2/4mRNA expression in the liver of AHNP rats was measured by RT-PCR.


RESULTS
Expression of TLR2/4mRNA could be detected in the liver of AHNP rats in sham-operated group (0.155E-5+/-0.230E-6 and 0.115E-2+/-0.545E-4), but was markedly increased at 3 h in AHNP group (0.197E-2+/-0.114E-3 and 0.175+/-0.349E-2) peaking at 12 h (0.294E-2+/-0.998E-4 and 2.673+/-2.795E-2, P<0.01). Hepatic injuries were aggravated, TNF-alpha concentration in the liver was increased and NO concentration was decreased (P<0.05 or P<0.01). When TLR2/4mRNA expression was inhibited by CQ (3 h: 1.037E-4+/-3.299E-6 and 0.026+/-3.462E-3; 6 h: 1.884E-4+/-4.679E-6 and 0.108+/-6.115E-3; 12 h: 2.443E-4+/-7.714E-6 and 0.348+/-6.807E-3; P<0.01), hepatic injuries were relieved, NO concentration in the liver was increased and TNF-alpha concentration was decreased (P<0.05 or P<0.01). When rats with AHNP were treated with L-Arg, TLR2/4mRNA expression in the liver could be effectively inhibited (50 mg-T: 0.232E-2+/-0.532E-4 and 0.230+/-6.883E-3; 100 mg-T: 0.210E-2+/-1.691E-4 and 0.187+/-0.849E-2; 200 mg-T: 0.163E-2+/-0.404E-4 and 0.107+/-0.195E-2; 400 mg-T: 0.100E-2+/-0.317E-4 and 0.084+/-0.552E-2; P<0.01) and hepatic injuries were relieved. At the same time, NO concentration in the liver was markedly increased and TNF-alpha concentration was decreased (P<0.05 or P<0.01).


CONCLUSIONS
The expression of TLR2/4mRNA is increased and hepatic injuries are aggravated in the liver of AHNP rats. TLR2/4mRNA gene expression in the liver of AHNP rats can be markedly inhibited by NO, leading to the relief of hepatic injuries.
Zhang
Lei
L
Center of Pancreatic Surgery, Affiliated Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
Wu
He-Shui
HS
Chen
Yan
Y
Guo
Xing-Jun
XJ
Wang
Lin
L
Wang
Chun-You
CY
Zhang
Jing-Hui
JH
Tian
Yuan
Y
D000410:Alanine Transaminase / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D006470:Hemorrhage / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000681:Amylases