乌司他丁联合谷氨酰胺对脓毒症大鼠免疫系统及炎症反应的影响
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摘要
目的:研究乌司他丁联合谷氨酰胺对脓毒血症大鼠炎症反应和免疫系统的影响。方法:将60只大鼠制作成脓毒血症大鼠和胃造瘘模型,随机分为对照组、乌司他丁组、谷氨酰胺组及乌司他丁联合谷氨酰胺组,每组15例。建模后立即给予生理盐水,乌司他丁、谷氨酰胺及乌司他丁联合谷氨酰胺,于治疗后6h,12h,24h检测CD4、CD8、降钙素原、白介素-6水平。结果:(1)降钙素原含量变化:乌司他丁组、谷氨酰胺组、联合组与对照组比较,在任一时间点降钙素原都显著降低(P<0.01);联合组较乌司他丁组和谷氨酰胺组相比,降钙素原值均降低(P<0.05);(2)IL-6的含量变化:乌司他丁组、谷氨酰胺组、联合组与对照组比较,在任一时间点IL-6都显著降低(P<0.01);联合组较乌司他丁组和谷氨酰胺组相比,IL-6值均降低(P<0.05);(3)CD4/CD8比值的变化:乌司他丁组、谷氨酰胺组、联合组与对照组比较,在任一时间点三个指标都显著升高(P<0.01);联合组较乌司他丁组和谷氨酰胺组相比,三个指标均降低(P<0.05);结论:乌司他丁联合谷氨酰胺较单一用药能够抑制脓毒血症大鼠炎性反应的过度发生,增强脓毒血症发生时免疫应答。
Objective:To investigate the effects of ulinastatin and glutamine on inflammatory responses and immune system in sepsis rats. Methods: A total of 60 SD clean male rats were made into a rat model of caecum perforation sepsis. Meanwhile, gastric draining tubes were placed at the same time. They were randomly divided into control group, ulinastatin group, glutamine group and ulinastatin plus glutamine group, and there were 4 groups, 15 cases in each group. After modeling, normal saline, ulinastatin, glutamine and ulinastatin combined with glutamine were given immediately after treatment. The levels of CD4, CD8, procalcitonin(PCT) and interleckin-6 were measured by 6 h, 12 h and 24 h respectively. Results:(1) There were changes in PCT content. Compared with the control group, PCT significantly decreased in ulinastatin group, glutamine group, and combined group(P<0.01); compared with the ulinastatin group and the glutamine group, the PCT value in the combined group decreased(P<0.05);(2) There were changes in the content of IL-6. Compared with the control group, in ulinastatin group, glutamine group, and combined group, IL-6 significantly decreased at any time point(P<0.01); compared with the ulinastatin group and the glutamine group, the IL-6 value decreased in the combined group(P<0.05).(3) There were the changes of the CD4/CD8 ratio. The CD4/CD8 ratio in the ulinastatin group, the glutamine group and the combined group was significantly higher than that of the control group(P<0.01) at any time point(P<0.01). Compared with the ulinastatin group and the glutamine group, the three indexes were lower in the combined group(P<0.05). Conclusion: Ulinastatin combined with glutamine can inhibit the excessive occurrence of inflammatory reactions in sepsis rats and enhance the immune response when sepsis occurs.
Objective:To investigate the effects of ulinastatin and glutamine on inflammatory responses and immune system in sepsis rats. Methods: A total of 60 SD clean male rats were made into a rat model of caecum perforation sepsis. Meanwhile, gastric draining tubes were placed at the same time. They were randomly divided into control group, ulinastatin group, glutamine group and ulinastatin plus glutamine group, and there were 4 groups, 15 cases in each group. After modeling, normal saline, ulinastatin, glutamine and ulinastatin combined with glutamine were given immediately after treatment. The levels of CD4, CD8, procalcitonin(PCT) and interleckin-6 were measured by 6 h, 12 h and 24 h respectively. Results:(1) There were changes in PCT content. Compared with the control group, PCT significantly decreased in ulinastatin group, glutamine group, and combined group(P<0.01); compared with the ulinastatin group and the glutamine group, the PCT value in the combined group decreased(P<0.05);(2) There were changes in the content of IL-6. Compared with the control group, in ulinastatin group, glutamine group, and combined group, IL-6 significantly decreased at any time point(P<0.01); compared with the ulinastatin group and the glutamine group, the IL-6 value decreased in the combined group(P<0.05).(3) There were the changes of the CD4/CD8 ratio. The CD4/CD8 ratio in the ulinastatin group, the glutamine group and the combined group was significantly higher than that of the control group(P<0.01) at any time point(P<0.01). Compared with the ulinastatin group and the glutamine group, the three indexes were lower in the combined group(P<0.05). Conclusion: Ulinastatin combined with glutamine can inhibit the excessive occurrence of inflammatory reactions in sepsis rats and enhance the immune response when sepsis occurs.
引文
[1] Venet F, Monneret G. dvances in the understanding and treatment of sepsis-induced immunosuppression[J]. Nat Rev Nephrol. 2018,14(2):121-137.
[2] Liu S, Wei F, Luo L.Ulinastatin attenuates hyper-permeability of vascular endothelialium cells induced by serum from patients with sepsis [J]Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi.2017,33(12):1600-1604.
[3] 黄丹,王学东.谷氨酰胺对脓毒症患者肠粘膜屏障功能和免疫功能的影响[J].现代生物医学进展,2015,15(14):2733-2735.
[4] Shankar-Hari M, Deutschman CS, Singer M. Do we need a new definition of sepsis [J].Intensive Care Med,2015,41(5): 909-911.
[5] Drifte G, Dunn-Siegrist I, Tissieres P,et al. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome[J]. Crit Care Med,2013,41(3) : 820-832.
[6] Delano MJ, Ward PA. Sepsis-induced immune dysfunction : can immune therapies reduce mortality[J].J Clin Invest,2016,126(1) : 23-31.
[7] 杨钊斌,陈雯雯,陈权,等,通过LPS造成小鼠脓毒症模型探讨小鼠腹腔巨噬细胞的自噬在免疫功能变化中的动态意义[J].免疫学杂志,2018,34(1):27-33.
[8] Sridharan P, Chamberlain RS. The efficacy of procalcitonin as a biomarker in themanagement of sepsis:slaying dragons or tilting at windmills [J].Surg Infect,2013,14(6):489-511.
[9] GP de Oliveira, JD Silva, CC de Araújo. Intravenous glutamine administration reduces lung and distal organ injury in malnourished rats with sepsis [J].Shock,2014,41(3):222-232.
[10] 叶亚玲,王自蕊,游金明,等.丙氨酰-谷氨酰胺对小鼠黏膜固有层免疫球蛋白A浆细胞数量、分泌型免疫球蛋白A及黏膜中白细胞介素含量的影响[J].营养报,2015,27(1):59-66.
[11] Karnad DR, Bhadade R, Verma PK,et al. Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study[J].Intensive Care Med,2014,40(6):830-838.
[12] L Jiang, L Yang, M Zhang. Beneficial effects of ulinastatin on gut barrier function in sepsis[J].Indian Journal of Medical Research,2013,138(6):904-911.
[2] Liu S, Wei F, Luo L.Ulinastatin attenuates hyper-permeability of vascular endothelialium cells induced by serum from patients with sepsis [J]Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi.2017,33(12):1600-1604.
[3] 黄丹,王学东.谷氨酰胺对脓毒症患者肠粘膜屏障功能和免疫功能的影响[J].现代生物医学进展,2015,15(14):2733-2735.
[4] Shankar-Hari M, Deutschman CS, Singer M. Do we need a new definition of sepsis [J].Intensive Care Med,2015,41(5): 909-911.
[5] Drifte G, Dunn-Siegrist I, Tissieres P,et al. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome[J]. Crit Care Med,2013,41(3) : 820-832.
[6] Delano MJ, Ward PA. Sepsis-induced immune dysfunction : can immune therapies reduce mortality[J].J Clin Invest,2016,126(1) : 23-31.
[7] 杨钊斌,陈雯雯,陈权,等,通过LPS造成小鼠脓毒症模型探讨小鼠腹腔巨噬细胞的自噬在免疫功能变化中的动态意义[J].免疫学杂志,2018,34(1):27-33.
[8] Sridharan P, Chamberlain RS. The efficacy of procalcitonin as a biomarker in themanagement of sepsis:slaying dragons or tilting at windmills [J].Surg Infect,2013,14(6):489-511.
[9] GP de Oliveira, JD Silva, CC de Araújo. Intravenous glutamine administration reduces lung and distal organ injury in malnourished rats with sepsis [J].Shock,2014,41(3):222-232.
[10] 叶亚玲,王自蕊,游金明,等.丙氨酰-谷氨酰胺对小鼠黏膜固有层免疫球蛋白A浆细胞数量、分泌型免疫球蛋白A及黏膜中白细胞介素含量的影响[J].营养报,2015,27(1):59-66.
[11] Karnad DR, Bhadade R, Verma PK,et al. Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study[J].Intensive Care Med,2014,40(6):830-838.
[12] L Jiang, L Yang, M Zhang. Beneficial effects of ulinastatin on gut barrier function in sepsis[J].Indian Journal of Medical Research,2013,138(6):904-911.