[Effect and significance of anisodamine on IkappaB kinase-beta in Kupffer cells following hemorrhagic shock].
OBJECTIVE
To investigate the possible role of IkappaB kinase-beta (IKK-beta), the pathogenesis of hepatic injury induced by resuscitation of hemorrhagic shock and endotoxin, and to evaluate the preventive effect of anisodamine (654-2).


METHODS
Twenty-seven rabbits were randomly divided into the normal group, hemorrhagic shock plus endotoxin group and 654-2 treatment group. The expression of IKK-beta, activity of the nuclear factor-kappaB (NF-kappaB) in Kupffer cells (KC) and the concentration of tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant were measured by in situ hybridization (ISH), electrophoretic mobility shift assay (EMSA) and enzyme linked immunoadsorbent analysis (ELISA), respectively. The pathological changes in the hepatic tissue were examined with light microscope.


RESULTS
Compared with the normal group, the expression of IKK-beta (0.21+/-0.03), the activity of NF-kappaB (2.29+/-0.25) in KC, and the level of TNF-alpha[(560.21+/-31.04) ng/L] in the culture supernatant of KC were obviously increased after hemorrhagic shock and endotoxin(all P<0.01 ). 654-2 treatment could significantly inhibit the expression of IKK-beta (0.14+/-0.03) and the activity of NF-kappaB (1.35+/-0.17) in KC, decrease the content of TNF-alpha [(300.79+/-23.47) ng/L] in the culture supernatant of KC in rabbits with hemorrhagic shock plus endotoxin challenge (all P<0.01 ),and alleviate hepatic injury as observed by histological examination.


CONCLUSIONS
IKK-beta expression in KC could be enhanced after hemorrhagic shock and endotoxin, and it might play an important role in the development and progression of hepatic injury following hemorrhagic shock and endotoxin. 654-2 could inhibit IKK-beta expression, decrease NF-kappaB activation and cytokine secretion in KC after hemorrhagic shock followed by resuscitation and endotoxin. The inhibition of IKK-beta expression might be a protective mechanism for hepatic injury.
Yuan
Jing
J
Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shanxi, China.
Zhang
Dong-tao
DT
Yin
Wen
W
Zhang
Jin-shan
JS
Zhang
Yuan-qiang
YQ
D000818:Animals; D051550:I-kappa B Kinase / Q000378:metabolism*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011817:Rabbits; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D012991:Solanaceous Alkaloids; D014409:Tumor Necrosis Factor-alpha; C003922:anisodamine; D051550:I-kappa B Kinase