- 作者: David Wang Jeng Wei Kang Hsu Jin-Chi Jau Mei-Wen Lieu Tai-Jong Chao Hsing I. Chen
- 作者服務機構: Department of Medical Research, Cheng Hsin General Hospital, Taipei, Department of Physiology National Defense Medical Center, Taipei, and Department of Physiology, Tzu Chi College of Medicine, Huallen, Taiwan, Republle of china
- 中文摘要: --
- 英文摘要: Endotoxin shock is characterized by systemic hypoten-sion, hyporeactive ness to vasoconstrictors and acutelung edema. A nitric oxide synthase(NOS)inhibitor, N -monomethyl-L-arginine(L-NMMA) has been shown tobe effective in reversing acute lung injury. In the presentstudy, we evaluated the effects of NOS blockade by dif-ferent mechanisms on the endotoxin-induced changes.In anesthetized rats, lipopolysaccharide(LPS, Klebsiellapneumoniae) was administered intravenously in a doseof 10 mg/kg. LPS caused sustained systemic hypoten-sion accompanied by an eightfold increase of exhaledNO during an observation period of 4 h. After the experi-ment, the lung weight was obtained and lung tissueswere taken for the determination of mRNA expressionsof inducible NOS(iNOS), interleukin-1β(IL-1β)and tumornecrosis factor-α-(TNF-α). Histological examination ofthe lungs was also performed. In the control groupinjected with saline solution, mRNA expressions ofiNOS, IL-1β and TNF-α were absent. Four hours afterLPS, the mRNA expressions of iNOS and IL-1β were stillsignificantly enhanced, but TNF-α was not discerniblyexpressed. LPS also caused a twofold increase in lungweight. Pathological examination revealed endothelialdamage and interstitial edema. Various NOS inhibitorswere given 1 h after LPS administration. These agentsincluded N -nitro-L-arginine methyl ester(L-NAME, 10mg/kg), a constitutive NOS and iNOS inhibitor; S,S'-1,4-phenylene-bis-(1,2-ethanedinyl)bis-isothiourea dihydro-bromide(1,4-PBIT, 10 mg/kg), a relatively specific iNOSinhibitor, and dexamethasone (3 mg/kg), an inhibitor ofiNOS expression. These NOS inhibitors all effectivelyreversed the systemic hypotension, reduced the exhaledNO concentration and prevented acute lung injury. TheLPS-induced mRNA expressions of iNOS and IL-1β werealso significantly depressed by these NOS inhibitors.Our results suggest that NO production through theiNOS pathway is responsible for endotoxin-induced lunginjury. Certain cytokines such as IL-1β are possibly in-volved. These changes are minimized by NOS inhibitorsthrough different mechanisms.
- 中文關鍵字: --
- 英文關鍵字: Lung injury. Nitric oxide synthase inhibitors. Nitric oxide. IL-1