| Summary: | 博士 === 中國醫藥大學 === 中國醫學研究所博士班 === 94 === AbstractThe high mortality rate of sepsis is always a difficult problem to overcome in clinic. Because the course of sepsis is developed fast and the pathophisiology turns complicated, it is difficult to control in treating. After sepsis happens, the uncontrollable cytokine storm is the important reason of patient''s death, so the change of proinflammatory and anti-inflammatory cytokines is the important key whether the condition worsens. To understand the importance of proinflammatory and anti-inflammatory cytokines in mortality, the study chooses IL-6 and IL-10 to represent proinflammatory and anti-inflammatory cytokines respectively. We use these two factors to evaluate prognosis accuracy first, and then regard traditional Chinese medicine as verification tool in treatment. The baseline values of IL-6 and IL-10 were measured by collecting blood with mouse tail artery after anesthetizing. The first part is the evaluation of prognosis: 35 Sprague-Dawley rats, weighing in between 250 to 300g, underwent cecal ligation and puncture (CLP) procedures and femoral arterial catheterization. When the heart rates reached 1.15, 1.25 and 1.35 times that of the baseline heart rate, blood sampling was done for IL-6 and IL-10. The prognosis was followed up for 3 days after CLP, and all rats were then divided into survival or non-survival groups. Finally, the relationships among survival condition, heart rate, IL-6, and IL-10 were analyzed by two-way ANOVA and multiple comparison. A linear discriminant function for the prognosis of sepsis was developed by IL-6 and IL-10 at different heart rates. Second part: the treatment of single flavor traditional Chinese medicine gypsum: Seventy-two rats were randomly assigned to three groups: control group, low dose treatment group and high dose treatment group. Sepsis was induced by cecal ligation and puncture. After 6 h, control group received normal saline 2.7cc/kg, low dose and high dose treatment groups received Gypsum 1.35cc/kg and 2.7cc/kg respectively. We observed three days for survival rate analysis. To realize the mechanism of gypsum further, we developed three groups randomly: control group (n=8), the most effective group (n=8) and sham group (n=5). Normal saline or gypsum was given subcutaneously 6h later. Inflammatory cytokines IL-6 and IL-10 were measured before CLP and every 4 h after CLP for 24 h. Blood pressure and heart rate were also measured every 4 h after CLP for 24 h. The third part: to realize the mechanism of Pai-hu-tang further, we developed two groups randomly: control group (n=6) and treatment group (n=6). Normal saline or Pai-hu-tang was given subcutaneously 6h later. Inflammatory cytokines IL-6 and IL-10 were measured before CLP and every 4 h after CLP for 24 h. Blood pressure and heart rate were also measured every 4 h after CLP for 24 h. The result shows: First part: IL-6 elevated continuously with the increment of the heart rate in the non-survival group, but in the survival group, the IL-6 elevation started to fall when the heart rate reached 1.25 times; a similar trend was found in the change of IL-10. The prediction rate was 68.33% when the heart rate reached 1.15 times, and increased to 93.33% and 95.45% when heart rates reached 1.25 and 1.35 times respectively. Second part: 3-day survival rate in both treatment groups were higher than the control group. IL-6 levels were significantly higher in the control than in the treatment group at 12 h,16 h,20 h and 24 h. Though there was no significant difference between control and treatment groups, the IL-10 levels seemed to have a decreasing trend in the treatment group. There was no obvious increase in blood pressure among these three groups. Heart rate increased by time in control and treatment groups and had significant difference with sham group at 16 h, 20 h and 24 h. Third part: IL-6 levels were significantly higher in the control than in the treatment group at 12 h, 16 h,20 h and 24 h. IL-10 levels were significantly higher in the control than in the treatment group at 16 h, 20 h and 24 h. Conclusion: IL6 and IL10 are very effective to the mortality of sepsis. They are strongly correlated to the pathogenesis and treatment of sepsis. In the future, if we can pay attention to the dynamic change of these two cytokines, it may be valuable in the treatment of sepsis.
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