LPS (sign) LPS ( ) LPS 15 1 SOP LPS ( ) LPS 2 LPS (Szabo et al., 1993) LPS LPS BK PAF endothelin (modulators) enos NO enos NO SOP LPS enos NO LPS TNF-α IL-1 PAF 68
inos TNF-α IL-1 LPS inos NO 2 LPS inos NO K ATP channels 1996 Armstead cgmp K ATP channels (Armstead, 1996) NO K ATP channels (Miyoshi et al., 1994; Chen et al., 2000) NO/cGMP K ATP channels (Chen et al., 2000) (baroreflex) LPS (baroreceptor) TNF-α LPS 2 inos NO LPS 69
LPS NO LPS TNF-α NO TNF-α 1 NO 2 LPS macrophages TNF-α IL-1 inos NO LPS TNF-α 1 IL-1 inos NO NO NO LPS 15 TB\GB AG\TB ML\AG LPS 15 LPS NO LPS NO AG\TB ML\AG LPS 4 NO LPS 70
NO TB\GB NO NO GB K ATP channels NO inos TNF-α inos NO TNF-α (1) ML\AG ML TNF-α ( LPS TNF-α ) ML\AG NO ML TNF-α inos AG inos LPS (2) TB\GB LPS 4 TNF-α LPS 2 TNF-α ( TNF-α ) TB\GB NO (3) AG\TB TNF-α LPS 90 AG TNF-α AG\TB LPS AG inos AG 1992 Corbett AG IL-1β NOS arginine (Corbett et al., 1992) AG 71
AG inos (1) diamine oxidase histamine (2) advanced glycosylation end products (Nilsson, 1999) (3) catalase (Ou and Wolff, 1994) (4) ROS (Giardino et al., 1998) TB\GB LPS 4 TNF-α macrophages human promonocytic THP-1 cells (in vitro) β-adrenergic agonists incubated 8 24 TNF-α mrna (Severn et al., 1992; Farmer and Pugin, 2000) camp TNF-α camp NO LPS 6 (Imai et al., 1994) TB\GB 6 NO LPS LPS NE ( ) NO 72
BK histamine K ATP channels NE NE NE LPS 3 TNFα inos K ATP channels ( ) LPS (glomerular filtration rate, GFR) angiotensin endothelin 1 leukotrienes thromboxane A 2 (Badr, 1992) NO LPS inos mrna NO (Kilbourn et al., 73
1990) IL-6 (Fougueray et al., 1993; Donnahoo et al., 1999) NO Schwartz (1) enos inos NO enos (2) LPS enos inos (3) inos (Schwartz et al., 1997) LPS inos NO enos GFR ( macrophages ) ATP CO 2 (Kantrow et al., 1997) GOT GTP albumin GOT 74
LPS (hepatotoxicity) TNF-α TNF-α (reactive oxygen nitrogen species) 酶 (Stadler et al., 1992) TNF-α (Barton et al., 2001) NO (Titheradge, 1999) GPT AG\TB ML\AG TNF-α (ML) inos (AG) inos mrna (ML) camp (TB) TB\GB TNF-α NO (Wu et al., 2000) TB TNF-α IL-10 TB IL-10 Kupffer cells 75
TB\GB creatinine NO NO NO TB\GB superoxides (Fig. 13 and Fig. 18) TB IL-6 Nakamura TB LPS IL-6 camp TB PKA-cAMP IL-6 mitogen-activated protein kinase (MAPK) TNF-α IL-6 (Nakamura et al., 1999) TNF-α TB IL-6 TB\GB creatinine creatinine 0.1 mg/dl 25-35% 0.1 20 76
LPS A/G ratio A/G ratio ( ) A/G ratio (Fig. 21) albumins globulins PAF TxA 2 histamine BK 5-HT albumins ( albumins ) (hypovolemia) albumins albumins 20 6 albumins B cell γ -globulins ( IgA IgG ) A/G ratio albumins globulins A/G ratio albumins globulins 77
LPS LPS alpha-cells (glucagon) cortisol (fight or flight reaction) (1) TNF-α eicosanoids (Mandrup-Poulsen et al., 1990) (2) α β (3) glucagon (glucose uptake) (Stadler et al., 1995) LPS Kupffer (glucose transporters) (Spolarics et al., 1993) NO (Balon and Nadler, 1997) NO (glycogenolysis) (glyconeogenesis) (McCallum and Berry, 1973; Horton et al., 1994 a ; Horton et al., 1994 b ; Casada et al., 1996; Ceppi et al., 1996; Young and Leighton, 1998) TB\GB TB β 2 -adrenergic receptor adenylyl cyclase camp (glycogenolysis) 2 78
(negative feedback) 4 LPS GB ( LPS 120 ) beta-cells insulin AG\TB ML\AG LPS ( 3 h) AG\TB AG cnos (Kapur et al., 1997; Tada et al., 2000) AG inos cnos AG cnos ML\AG ML (LPS 1 ) corticosteroids (Ogle and Kitay, 1978) corticosteroids (Vaughan et al., 1972; Shima et al., 1997) NO (1) LPS NO NO NO (2) AG\TB ML\AG LPS NO LPS NO 79
NO TB\GB GB TB\GB TB ML LPS O - 2 O - 2 O - 2 nitrite O - 2 TB\GB LPS O - 2 NO IL-10 NO (Kuga et al., 1996; Dokka et al., 2001) ML O - 2 O - 2 O - 2 SOD H 2 O 2 酶 hydroxyl radical (OH - ) ML OH - indolyl cation radical O - 2 N-acethyl-N-formyl-5-methoxykynuramine ML ( ) ML ML inos 80
Gilad NFκB inos (transcription) (Gilad et al., 1998) Schreck NFκB NFκB inos gene (Schreck et al., 1991) ML\AG O - 2 NO ML O - 2 NFκB inos NO 60 ICR mice TB\GB ML\AG (83%) LPS (16%) 5 AG\TB (42%) LPS (16%) 2.6 ( table 4.) post-treatment 81
pre-treatment 82