P38MAPK抑制剂SB203580对大鼠重症急性胰腺炎脑损伤血清TNF-α、IL-1和IL-8水平变化的影响

发布时间：2018-05-24 04:09

本文选题：胰性脑病 + 重症急性胰腺炎脑损伤　；参考：《内蒙古医科大学》2017年硕士论文

【摘要】：目的:探讨p38MAPK抑制剂SB203580对大鼠重症急性胰腺炎脑损伤血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)及白细胞介素-8(IL-8)的水平变化的影响,分析各炎症因子与重症急性胰腺炎脑损伤病情的相关性,为重症急性胰腺炎脑损伤的诊断及治疗提供实验依据.方法:选取70只SD大鼠随机分为对照组(n=10)、重症急性胰腺炎脑损伤组(SAP组,n=30)和SB203580治疗组(SB组,n=30).SAP组及SB组大鼠均经腹腔注射雨蛙素6次,每次间隔1h,最后一次同时注射脂多糖,建立大鼠重症急性胰腺炎脑损伤模型。同样,对照组经腹腔穿刺注射6次等剂量生理盐水,SB组大鼠于造模前0.5h尾静脉注射p38MAPK抑制剂SB203580,各组大鼠均分别于术后3h、6h及12h处死,每时间段每组各处死10只大鼠(其中对照组仅一组10只,于注射后12h处死,同其他亚组对照)。分别取三组大鼠脑组织和胰腺组织,HE染色镜下观察其病理改变,检测血清淀粉酶、TNF-α、IL-1和IL-8的含量变化,并检测脑组织含水量变化。结果:随时间延长,脑细胞水肿,血清TNF-α和IL-8含量在造模后3h、6h、12h SAP组及SB组均较对照组显著增加(P均0.05),血清IL-1含量在造模后3h、6h、12h SAP组较对照组显著增加(P均0.05),对SAP组及SB组造模后3h、6h、12h分别采用两两比较LSD-t检验,随病情发展各因子出现不同变化。结论:雨蛙素联合脂多糖腹腔穿刺注射可以建立稳定的重症急性胰腺炎脑损伤的模型。随时间变化,大鼠血清淀粉酶、TNF-α、IL-1及IL-8的含量呈增高趋势,其胰腺及脑组织的病理变化呈加重趋势。应用SB203580可以降低大鼠血清淀粉酶、TNF-α、IL-1及IL-8的含量,可以减轻大鼠胰腺及脑组织的病理变化。其机制可能是抑制了p38MAPK信号转导通路。
[Abstract]:Objective: to investigate the effects of p38MAPK inhibitor SB203580 on the levels of serum tumor necrosis factor- 伪 (TNF- 伪), interleukin-1 (IL-1) and interleukin-8 (IL-8) in rats with severe acute pancreatitis. To analyze the correlation between inflammatory factors and brain injury in severe acute pancreatitis and to provide experimental basis for the diagnosis and treatment of brain injury in severe acute pancreatitis. Methods: seventy Sprague-Dawley rats were randomly divided into control group (n = 10), severe acute pancreatitis group (n = 30), SB203580 treatment group (n = 6), SB group (n = 30) and SB group (n = 6). To establish the brain injury model of severe acute pancreatitis in rats. Similarly, the rats in the control group were injected with SB203580 via caudal vein 0.5 h before the model, and the rats in each group were killed at 3 h, 6 h and 12 h, respectively. 10 rats were killed in each group (10 rats in the control group) were killed 12 hours after injection and compared with other subgroups. The histopathological changes were observed under HE staining in brain and pancreas tissues of three groups. The contents of serum amylase TNF- 伪 -1 and IL-8, and the changes of water content in brain tissue were also detected. Results: over time, brain cell edema, The levels of serum TNF- 伪 and IL-8 were significantly higher in the SAP group and SB group than in the control group at 3h, 6h and 12h after model making, respectively. The serum IL-1 content in the SAP group was significantly higher than that in the control group at 3h, 6h and 12h after model making. The LSD-t test was used to test the serum TNF- 伪 and IL-8 in the SAP group and the SB group at 3 h and 6 h after the model making, and 12 h after the establishment of the model, and the serum IL-1 content in the SB group was compared with that in the control group (P < 0.05). With the development of the disease, various factors appeared different changes. Conclusion: the stable brain injury model of severe acute pancreatitis can be established by intraperitoneal injection of Rain frog and lipopolysaccharide. Over time, the contents of serum amylase TNF- 伪, IL-1 and IL-8 increased, and the pathological changes of pancreas and brain tissue increased. The application of SB203580 can reduce the contents of serum amylase TNF- 伪 IL-1 and IL-8, and alleviate the pathological changes of rat pancreas and brain tissue. The mechanism may be the inhibition of p38MAPK signal transduction pathway.
【学位授予单位】：内蒙古医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R576

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