EFFECTS OF INTESTINAL LAVAGE ON PATIENTS WITH SEPTIC MULTIPLE ORGAN FAILURE

肠灌洗对脓毒性多器官衰竭患者的影响

• 批准号: 10671425
• 负责人: NOGUCHI Takayuki
• 金额: $ 1.86万
• 依托单位: OITA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671425/
• 关键词: MULTIPLE ORGAN FAILURE; HYPERBIRILUBINEMIA; sFas; NOx; DAO; HYPERCYTOKINEMIA; APOPTOSIS; WHOLE GUT LAVAGE; 高ビリルビン血症; 肝静脈内カテーテル; サイトカイン; 接着因子

1) In the present clinical study, the effects of plasma circulating inflammatory cytokines, plasma NOx levels and soluble Fas on acute lung injury and other organ failure were investigated in fifteen septic shock patients; seven patients were survivor and the other eight were nonsurvivor. The average PaO2/FIO2 ratio in nonsurvivors was lower than that in survivors (108±28 vs. 177±37; mean ±SD). Although plasma average Nox levels and sFas concentrations in nonsurvivors were much higher than those in survivors (Nox; 112.4±27.4 vs. 68.5 ±30.3 micro M/L, sFas; 3.3 ±1.2 vs. 1.4 ±0.5 U/ml), no correlation was found between PaO2/FIO2 ratio and Plasma Nox or sFas concentrations. In the present animal investigation, plasma inflammatory cytokines, plasma Nox levels, sFas and Fas expression in lung and liver tissues were investigated in cecal ligation and puncture (CLP) and liver ischemic reperfusion (I/R) rats. Although plasma levels of NOx in CLP rats were higher than those of I/R rats (33.5±2. … More 8 vs. 26.2±1.9 micro M/L), these values were considered minimal. Plasma sFas concentrations in CLP rats were lower than that in I/R rats. The expression of 66 kilodalton molecular weight Fas with Western blot in the lungs and the livers of CLP rats were less than that in I/R rats.The results of this clinical study and animal investigation suggest that a slightly elevated plasma Nox level has no effect on onset of acute lung injury and that apoptosis has only a slight effect on sepsis related lung injury in patients with sepsis but has some important effects on I/R related liver injury.2) Next, diamine oxidase (DAO) activity, IL-6, IL-8, IL-10 and sFas were measured in 14 septic patients with hyperbilirubinemia. The average total and direct bilirubin levels were 7.8±1.0mg/dl and 5.l±0.6mg/dl. The average IL-6, IL-8 and IL-10 were 146.8±35.3pg/ml, 120.6±14.4pg/ml and 197.5±43.5pg/ml, respectively. The average sFas level was 5.2±0.8ng/ml. Significant correlations were found in total birilubin value and sFas concentrations, IL-6/IL-10 and in DAO levels and sFas, IL-6/10 ratio.These results of this clinical study suggests that the increased plasma DAO level showed ischemic change in the gut and hyperbirirubinemia correlated to hypercytokinemia or apoptosis. But effects of gut lavage on hyperbirilubinemia could not be proven in this study, because only 4 patients with informed consent of this study were treated with hole gut lavage. Less

1)在本临床研究中，血浆循环炎性细胞因子，血浆氮氧化物水平和可溶性Fas在急性肺损伤和其他器官衰竭的15例感染性休克患者中的影响进行了研究，其中7例患者是幸存者，其他8例是非幸存者。死亡者的平均PaO 2/FIO 2比值低于存活者（108±28 vs. 177±37;均值±标准差）。虽然死亡者的血浆平均Nox水平和sFas浓度远高于存活者（Nox; 112.4±27.4 vs. 68.5 ±30.3 microM/L，sFas; 3.3 ±1.2 vs. 1.4 ±0.5 U/ml），但未发现PaO 2/FIO 2比值与血浆Nox或sFas浓度之间存在相关性。本实验观察了盲肠结扎穿孔（CLP）和肝脏缺血再灌注（I/R）大鼠血浆炎性细胞因子、血浆Nox水平及肝、肺组织sFas和Fas表达的变化。CLP大鼠血浆NOx水平虽高于I/R大鼠（33.5±2. ...更多信息 8与26.2±1.9 μ M/L），认为这些值极轻微。CLP大鼠血浆sFas浓度低于I/R大鼠。Western blot结果显示，CLP大鼠肺、肝组织中66 kD分子量的Fas表达均低于I/R大鼠。本临床研究和动物实验结果提示，血浆Nox水平轻度升高对脓毒症肺损伤的发生无影响，细胞凋亡对脓毒症相关肺损伤的发生有轻微影响，但对I/R大鼠有重要作用。检测14例脓毒症合并高胆红素血症患者血清二胺氧化酶（DAO）活性、IL-6、IL-8、IL-10及sFas水平。平均总胆红素和直接胆红素水平分别为7.8±1.0mg/dl和5.1 ±0.6mg/dl。IL-6、IL-8和IL-10平均值分别为146.8±35.3pg/ml、120.6±14.4pg/ml和197.5±43.5pg/ml。平均sFas水平为5.2±0.8ng/ml。血清总胆红素水平与sFas、IL-6/IL-10及DAO水平与sFas、IL-6/10比值均呈显著相关，提示血浆DAO水平升高提示肠道缺血性改变，高胆红素血症与高细胞因子血症或细胞凋亡有关。但是，由于本研究中只有4例知情同意的患者接受了孔式肠道灌洗治疗，因此本研究无法证明肠道灌洗对高胆红素血症的影响。少

项目成果

HIDEO IWASAKA: "Effects of apoptosis on ischemic reperfusion injury of the liver"Circulation Control. 20. 265-269 (1999)

HIDEO IWASAKA：“细胞凋亡对肝脏缺血再灌注损伤的影响”循环控制。

TAKAYUKI NOGUCHI: "The mechanism of sepsis induced ALI-with special reference to apoptosis and nitri oxide"Japanese Journal of Intensive Care Medicine. 23. 823-827 (1999)

野口 TAKAYUKI NOGUCHI：“脓毒症诱发 ALI 的机制——特别涉及细胞凋亡和一氧化氮”《日本重症监护医学杂志》。

野口隆之: "ALI-アポトーシスとNOの関係から"ICUとCCU. 23(11). 823-827 (1999)

Takayuki Noguchi：“ALI-来自细胞凋亡和NO之间的关系”ICU和CCU 823-827（1999）。

野口 隆之: "ALI-アポトーシスとNOの関係から"ICUとCCU. 23. 823-827 (1999)

Takayuki Noguchi：“ALI-从细胞凋亡与NO之间的关系”ICU和CCU。23。823-827（1999）。

岩坂日出男: "肝虚血再灌流障害におけるアポトーシスの関与とその制御"循環制御. 20. 265-269 (1999)

Hideo Iwasaka：“细胞凋亡及其在肝缺血再灌注损伤中的调节”循环控制。 20. 265-269 (1999)