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P38MAPK抑制劑SB203580對大鼠重癥急性胰腺炎腦損傷血清TNF-α、IL-1和IL-8水平變化的影響

發(fā)布時間:2018-05-24 04:09

  本文選題:胰性腦病 + 重癥急性胰腺炎腦損傷 ; 參考:《內(nèi)蒙古醫(yī)科大學(xué)》2017年碩士論文


【摘要】:目的:探討p38MAPK抑制劑SB203580對大鼠重癥急性胰腺炎腦損傷血清腫瘤壞死因子-α(TNF-α)、白細胞介素-1(IL-1)及白細胞介素-8(IL-8)的水平變化的影響,分析各炎癥因子與重癥急性胰腺炎腦損傷病情的相關(guān)性,為重癥急性胰腺炎腦損傷的診斷及治療提供實驗依據(jù).方法:選取70只SD大鼠隨機分為對照組(n=10)、重癥急性胰腺炎腦損傷組(SAP組,n=30)和SB203580治療組(SB組,n=30).SAP組及SB組大鼠均經(jīng)腹腔注射雨蛙素6次,每次間隔1h,最后一次同時注射脂多糖,建立大鼠重癥急性胰腺炎腦損傷模型。同樣,對照組經(jīng)腹腔穿刺注射6次等劑量生理鹽水,SB組大鼠于造模前0.5h尾靜脈注射p38MAPK抑制劑SB203580,各組大鼠均分別于術(shù)后3h、6h及12h處死,每時間段每組各處死10只大鼠(其中對照組僅一組10只,于注射后12h處死,同其他亞組對照)。分別取三組大鼠腦組織和胰腺組織,HE染色鏡下觀察其病理改變,檢測血清淀粉酶、TNF-α、IL-1和IL-8的含量變化,并檢測腦組織含水量變化。結(jié)果:隨時間延長,腦細胞水腫,血清TNF-α和IL-8含量在造模后3h、6h、12h SAP組及SB組均較對照組顯著增加(P均0.05),血清IL-1含量在造模后3h、6h、12h SAP組較對照組顯著增加(P均0.05),對SAP組及SB組造模后3h、6h、12h分別采用兩兩比較LSD-t檢驗,隨病情發(fā)展各因子出現(xiàn)不同變化。結(jié)論:雨蛙素聯(lián)合脂多糖腹腔穿刺注射可以建立穩(wěn)定的重癥急性胰腺炎腦損傷的模型。隨時間變化,大鼠血清淀粉酶、TNF-α、IL-1及IL-8的含量呈增高趨勢,其胰腺及腦組織的病理變化呈加重趨勢。應(yīng)用SB203580可以降低大鼠血清淀粉酶、TNF-α、IL-1及IL-8的含量,可以減輕大鼠胰腺及腦組織的病理變化。其機制可能是抑制了p38MAPK信號轉(zhuǎn)導(dǎo)通路。
[Abstract]:Objective: to investigate the effects of p38MAPK inhibitor SB203580 on the levels of serum tumor necrosis factor- 偽 (TNF- 偽), 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- 偽 -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- 偽 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- 偽 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- 偽, 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- 偽 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.
【學(xué)位授予單位】:內(nèi)蒙古醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R576

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