【摘要】：目的：探討烏司他丁對于重癥急性胰腺炎（severe acute pancreatitis，SAP）大鼠腸粘膜高遷移率族蛋白B1（high mobility group box-1protein，HMGB1）表達及對腸粘膜屏障的作用，旨在為SAP的臨床治療提供實驗依據。 方法：實驗動物選用雌性斯普拉-道來（Sprague dawley,SD）大鼠54只，清潔級，體重220-250g，平均體重237.45g。將實驗大鼠稱重后標號，隨機分為對照組、SAP組及烏司他丁干預組，每組18只，實驗前全部大鼠禁食12小時，但不禁飲水。運用穿刺十二指腸并逆行膽胰管注射�；悄懰徕c法[1]誘導建立大鼠SAP模型，對照組開腹并翻動胰腺組織兩三下后，逐層縫合切口。干預組于造模成功后5分鐘內，行尾緣靜脈注射烏司他�。�1000IU/100g體質量），10分鐘內注射完畢，對照組及SAP組分別于造模成功后5分鐘，行尾緣靜脈注射生理鹽水。每一組按造模成功后6小時、12小時、24小時分為3個時間亞組，每組6只，并按照上述時間點分3批處死大鼠，每批6只。使用生化分析儀檢測各組血清淀粉酶含量，觀察各組胰腺組織學變化，應用酶聯(lián)免疫吸附方法（ELISA）測定各組血清TNF-α含量，取小腸組織后勻漿并應用ELISA法測定腸道HMGB1濃度，分光光度法測腸粘膜二胺氧化酶（diamineoxidase，DAO）含量，同時測定腸道組織濕干比。 結果：造模時可見胰腺組織腫脹明顯，并有點狀出血，提示造模成功[1]。SAP組18只大鼠死亡10只，烏司他丁干預組死亡6只，對照組死亡3只，死亡大鼠被剔除后重新造模以補充數據。6小時對照組、SAP組及干預組血清淀粉酶、血清TNF-α含量、腸道HMGB1含量、腸粘膜二胺氧化酶含量、腸道組織濕干比和胰腺組織病理評分兩兩比較，差異有統(tǒng)計學意義(p0.05)。12小時對照組、SAP組及干預組上述指標兩兩比較，差異有統(tǒng)計學意義(p0.05)。24小時血清TNF-αSAP組與干預組相比差異無統(tǒng)計學意義(p0.05),但兩組與對照組相比差異有統(tǒng)計學意義(p0.05)。其余指標兩兩比較，差異有統(tǒng)計學意義(p0.05)。 結論：采用穿刺十二指腸逆行膽胰管注射�；悄懰徕c法可成功制造出SAP動物模型。烏司他丁可減少致炎因子HMGB1在腸道組織的表達，減少二胺氧化酶在腸粘膜的丟失，降低腸道組織濕干比，保護腸道粘膜屏障功能。
[Abstract]:Objective: to investigate the effect of ulinastatin on the expression of intestinal mucosal high mobility group protein B1 (high mobility group box-1protein,HMGB1 and intestinal mucosal barrier in rats with severe acute pancreatitis (severe acute pancreatitis,SAP), in order to provide experimental evidence for the clinical treatment of SAP. Methods: Fifty-four female Sprague dawley,SD rats, weighing 220-250 g, were selected as experimental animals, with an average weight of 237.45 g. After weighing the experimental rats were randomly divided into control group, SAP group and ulinastatin intervention group, 18 rats in each group. All rats fasted for 12 hours before the experiment, but could not help drinking water. The rat SAP model was induced by injection of sodium taurocholate into the duodenum and retrograde cholangiopancreatic duct. In the control group, the abdominal cavity was opened and the pancreatic tissue was turned over for two or three times, and the incision was sutured layer by layer. In the intervention group, ulinastatin (1000IU/100g body mass) was injected intravenously in the caudal margin within 5 minutes after the successful modeling, and the control group and the SAP group were injected with normal saline in the caudal vein within 5 minutes after the successful establishment of the model. Each group was divided into 3 subgroups according to 6 hours, 12 hours and 24 hours after successful modeling, 6 rats in each group were killed in 3 batches according to the above time points, 6 rats were killed in each batch. The content of serum amylase in each group was detected by biochemical analyzer, and the histological changes of pancreas in each group were observed. The content of TNF- 偽 in serum of each group was determined by enzyme linked immunosorbent assay (ELISA), the homogenate of small intestine tissue was taken out and the concentration of HMGB1 in intestine was determined by ELISA method. The content of diamine oxidase (diamineoxidase,DAO) in intestinal mucosa and the wet / dry ratio of intestinal tissue were measured by spectrophotometry. Results: the pancreatic tissue swelling and punctate hemorrhage could be seen in the model making. [1] .Eighteen rats died in SAP group, 6 rats in ulinastatin intervention group and 3 rats in control group. Serum amylase, serum TNF- 偽, intestinal HMGB1 and intestinal mucosal diamine oxidase were found in 6 hour control group, SAP group and intervention group. The wet-to-dry ratio of intestinal tissue and the pathological score of pancreatic tissue were significantly different (p0.05). The above indexes were compared in 12 hours control group, SAP group and intervention group. There was no significant difference between the 24 hour serum TNF- 偽 SAP group and the intervention group (p0. 05), but there was a significant difference between the two groups and the control group (p0. 05). There was significant difference between the other indexes (p 0.05). Conclusion: SAP animal model can be successfully established by injection of sodium taurocholate into retrograde cholangiopancreatic duct of duodenum. Ulinastatin could reduce the expression of HMGB1 in intestinal tissue, decrease the loss of diamine oxidase in intestinal mucosa, decrease the wet / dry ratio of intestinal tissue, and protect intestinal mucosal barrier function.
【學位授予單位】：皖南醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R965

【參考文獻】

相關期刊論文 前10條

1 黎君友，于燕，郝軍，，晉樺，許惠君;分光光度法測定血和小腸組織二胺氧化酶活性[J];氨基酸和生物資源;1996年04期

2 唐晉;宋孟龍;程飛;張獻全;;大承氣湯治療重癥急性胰腺炎大鼠的實驗研究[J];重慶醫(yī)學;2010年09期

3 ;Low-dose dopamine reduces inflammatory factors of acute pancreatitis in rats[J];Hepatobiliary & Pancreatic Diseases International;2007年06期

4 刁春香,商弘,王世龍;善得定與洛塞克聯(lián)合治療重癥胰腺炎[J];黑龍江醫(yī)學;2002年07期

5 萬美華;李娟;唐文富;龔翰林;陳光遠;薛平;趙先林;夏慶;;大承氣湯對急性胰腺炎致急性肺損傷-腹內高壓的作用[J];四川大學學報(醫(yī)學版);2011年05期

6 方立峰;;烏司他丁治療急性壞死性胰腺炎的實驗研究[J];局解手術學雜志;2008年04期

7 李君久,覃謙,王力斌,李洪;生長抑素治療輕型急性胰腺炎的療效研究[J];寧夏醫(yī)學雜志;2004年03期

8 欒正剛;張成;葛春林;馬曉春;郭仁宣;;重癥急性胰腺炎大鼠HMGB1表達與腸黏膜屏障損害的關系[J];中國現(xiàn)代普通外科進展;2008年01期

9 林棟棟,孫家邦,李非,張淑文,崔葉青,劉大川,朱斌,孫海晨,劉爽;IL-8、IL-10在大鼠急性胰腺炎并發(fā)肺損傷中的作用[J];首都醫(yī)科大學學報;2005年02期

10 張明鈞;姚瑋艷;喬敏敏;諸琦;袁耀宗;;腸壁穿刺逆行胰膽管注射牛黃膽酸鈉重癥急性胰腺炎造模[J];上海交通大學學報(醫(yī)學版);2006年05期

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