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- 저자 : 임홍섭(Hong Sed Lim) (검색결과 1 건)
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내독소에 의한 다발성 기관기능장애의 발생에 있어서 Pentoxifylline 의 치료효과에 관한 연구
이겸철(Gyum Cjheol Lee),정승수(Sung Soo Jeong),김충기(Chung Kee Kim),서대홍(Dae Hong Su),임홍섭(Hong Sed Lim),김치대(Chi Dae Kim),홍기환(Ki Whan Hong) 대한내과학회 1998 대한내과학회지 Vol.54 No.5
N/A Objectives : Septic shock is characterized by the circulatory failure including vasodilation, hyporeactivity to vasoconstrictor agents and organ ischemia in association with multiple organ failure and increased platelet aggregation and blood coagulation. In the present study, we investigated the preventive effects of N-nitro- L-arginine methyl ester (I -NAME, 30mg/kg, i.p.), a non-selective nitric oxide synthase (NOS) inhibitor, S -methylisothiourea sulfate (SMT, 5mg/kg, i.p.) and pentoxifylline (PTX, 10mg/kg, i.p.) on the multiple organ dysfunction in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide: LPS) and discussed the mechanism underlying the development of multiple organ failure. Methods . The effect of each other Nw-nitro-L- arginine methyl ester(L- NAME, 30 mg/kg, i.p.), a non- selective nitric oxide synthase(NOS) inhibitor, S-methylisothiourea sulfate(SMT, 5mg/kg, i.p.) and pentoxifylline (PTX, 10mg/kg, i.p.) were comparatively evaluated following inducing circulatory shock by means of infusion of bacterial endotoxin to thc rat model. Results : 1) The systemic mean arterial blood pressure deamsed by 48.7mmHg and vascular hyporeactivity to oradrenaline injection(l㎍/kg, i.v.) upon intravenous administration of LPS. 2) Endotoxemia for 6hours resulted in little change in the numbers of white blood cells and neutrophils but a significant reduction in the numbers of platelets. The variables were not affected by the inhibitors. 3) Endotoxemia for 6hours caused a significant increase in serum nitric oxide level (P<0.01) which was inhibited by SMT, but not by L-NAME and PTX. 4) Upon injection of LPS, serum creatinine(0,65± 0.08mg/dl) and urea(28.7±5.9mg/dl) were significantly elevated to 0.92±0.12 (P<0.05) and 54.3±2.1mg/dl (P< 0.01). These elevated levels were significantly attenuated by PTX but not by L-NAME and SMT. 5) Endotoxemia for 6 hours resulted in a significant increases in serum ALT(988.8±28.2 1U/L, P<0.01) and AST levels(l470.5±396.5 IU/I., P<0.01) from basal levels of ALT(67.8+ 11.7IU/I.) and AST(170.3±14.8IU/L). These increased activities were significantly attenuated by PTX, but not by L-NAME and SMT. The level of LDH(1279.8 ±156.2IU/L) was significantly increased by I.PS treatment to 2932.0519.9IU/L (P<0.05), which was inhibited by PTX. 6) Upon LPS treatnt, the myeloperoxidase activity in the lung homogenate was significantly increased by I.PS treatment (P<0.05), whereas that in the liver showed less change. The increased activity was reduced by PTX (P<0.05), but not by L-NAME and SMT. 7) The level of serum malondialdehyde, an index of lipid peroxidation by oxygen free radicals, was little influenced by LPS. Conelusion : Based on these results, it is summarized that PTX characteristically inhibited the development of multiple ogran dysfunction in a murine model of endotoxemia. Thus, it is concluded that the formation of TNF and increased activity of neutrophils may importantly contribute to the development of LPS-induced endotoxemia.
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