中国实用医刊
中國實用醫刊
중국실용의간
CENTRAL PLAINS MEDICAL JOURNAL
2011年
6期
23-25
,共3页
P38丝裂原活化蛋白激酶%重症急性胰腺炎%肿瘤坏死因子%凋亡
P38絲裂原活化蛋白激酶%重癥急性胰腺炎%腫瘤壞死因子%凋亡
P38사렬원활화단백격매%중증급성이선염%종류배사인자%조망
P38 mitogen-activated protein kinase%Severe acute pancreatitis%Twnor necrosis factor%Apoptosis
目的 探讨P38丝裂原活化蛋白激酶(P38MAPK)抑制剂(SB203580)对重症急性胰腺炎的治疗作用.方法 将Wistar大鼠63只随机分为三组:假手术组(S组),重症急性胰腺炎组(P组),SB203580处理组(T组),每组21只.SAP模型由5%牛磺胆酸钠大鼠胆胰管逆行注射诱发而成.模型成功后,P组不做处理;T组立即行SB203580 10 mg/kg腹腔注射;S组仅开腹,不做其他处理;术后各组于1 h、2 h、4 h 3个时间点处死大鼠,各时间点酶联免疫吸附测定(ELISA)法测血清TNF-α水平,并取胰腺组织行病理检查,免疫组化法检测p-P38MAPK表达,TUNEL法检测胰腺腺泡细胞凋亡.结果 血清TNF-α水平随SAP病情的进展而升高(P＜0.05),其水平P组及T组各时间点均较S组高,但TNF-α水平T组各时间点显著低于P组(P＜0.05);p-P38MAPK表达随SAP病情进展而升高(P＜0.05),1、2、4 h三个时间点P组及T组均升高(P＜0.05),但T组活性显著低于P组(P＜0.05):TUNEL显示假手术组胰腺组织存在极少量的凋亡细胞,T、P组细胞凋亡率均高于S组,T组凋亡率高于P组(P＜0.05);胰腺病理损害光镜下T组明显轻于P组.结论 P38MAPK可能参与大鼠重症急性胰腺炎发病过程,SB203580可能通过抑制P38MAPK活化减少炎症递质释放,增加胰腺腺泡细胞凋亡,减轻SAP病理损害.
目的 探討P38絲裂原活化蛋白激酶(P38MAPK)抑製劑(SB203580)對重癥急性胰腺炎的治療作用.方法 將Wistar大鼠63隻隨機分為三組:假手術組(S組),重癥急性胰腺炎組(P組),SB203580處理組(T組),每組21隻.SAP模型由5%牛磺膽痠鈉大鼠膽胰管逆行註射誘髮而成.模型成功後,P組不做處理;T組立即行SB203580 10 mg/kg腹腔註射;S組僅開腹,不做其他處理;術後各組于1 h、2 h、4 h 3箇時間點處死大鼠,各時間點酶聯免疫吸附測定(ELISA)法測血清TNF-α水平,併取胰腺組織行病理檢查,免疫組化法檢測p-P38MAPK錶達,TUNEL法檢測胰腺腺泡細胞凋亡.結果 血清TNF-α水平隨SAP病情的進展而升高(P＜0.05),其水平P組及T組各時間點均較S組高,但TNF-α水平T組各時間點顯著低于P組(P＜0.05);p-P38MAPK錶達隨SAP病情進展而升高(P＜0.05),1、2、4 h三箇時間點P組及T組均升高(P＜0.05),但T組活性顯著低于P組(P＜0.05):TUNEL顯示假手術組胰腺組織存在極少量的凋亡細胞,T、P組細胞凋亡率均高于S組,T組凋亡率高于P組(P＜0.05);胰腺病理損害光鏡下T組明顯輕于P組.結論 P38MAPK可能參與大鼠重癥急性胰腺炎髮病過程,SB203580可能通過抑製P38MAPK活化減少炎癥遞質釋放,增加胰腺腺泡細胞凋亡,減輕SAP病理損害.
목적 탐토P38사렬원활화단백격매(P38MAPK)억제제(SB203580)대중증급성이선염적치료작용.방법 장Wistar대서63지수궤분위삼조:가수술조(S조),중증급성이선염조(P조),SB203580처리조(T조),매조21지.SAP모형유5%우광담산납대서담이관역행주사유발이성.모형성공후,P조불주처리;T조립즉행SB203580 10 mg/kg복강주사;S조부개복,불주기타처리;술후각조우1 h、2 h、4 h 3개시간점처사대서,각시간점매련면역흡부측정(ELISA)법측혈청TNF-α수평,병취이선조직행병리검사,면역조화법검측p-P38MAPK표체,TUNEL법검측이선선포세포조망.결과 혈청TNF-α수평수SAP병정적진전이승고(P＜0.05),기수평P조급T조각시간점균교S조고,단TNF-α수평T조각시간점현저저우P조(P＜0.05);p-P38MAPK표체수SAP병정진전이승고(P＜0.05),1、2、4 h삼개시간점P조급T조균승고(P＜0.05),단T조활성현저저우P조(P＜0.05):TUNEL현시가수술조이선조직존재겁소량적조망세포,T、P조세포조망솔균고우S조,T조조망솔고우P조(P＜0.05);이선병리손해광경하T조명현경우P조.결론 P38MAPK가능삼여대서중증급성이선염발병과정,SB203580가능통과억제P38MAPK활화감소염증체질석방,증가이선선포세포조망,감경SAP병리손해.
Objective To explore the therapeutic effect of P38 mitogen-activated protein kinase (MAPK) inhibitor(SB203580) on severe acute pancreatitis(SAP). Methods Sixty-three Wistar rats were randomly allocated into three groups: sham operation group (group S), SAP group (group P),treatment group with SB203580 (group T). There were 21 rats in each group. Rat SAP model was induced by retrograde injection of 5% sodium taurocholate to pancreatic duct. After the model was successfully established, no treatments were given in group P. In group T, SB203580 ( 10 rmg/ml) was given by intraperitoneal injection(10 mg/kg). The rats in group S were only subjected to abdominal opening surgery. The rats were killed 1 h, 2 h and 4 h after operation. Serum levels of tumor necrosis factor-α (TNF-α) were measured by ELISA. The pancreas tissues were obtained to examine the changes with microscope, the expression of p-P38MAPK was examined by immunohistochemical technique and apoptosis of pancreatic acinar cells was detected by TUNEL methods. Results At the three time points, the levels of TNF-α and the activity of P38MAPK in group P andgroup T were significantly increased compared with those in group S ( P ＜0.05 ). In group T, the levels of TNF-α and the activity of P38MAPK were significantly decreased compared with those in group P(P＜0.05), the apoptosis rate of pancreatic acinar cell was significantly higher than those in group P ( P ＜ 0. 05 ). Pancreatic pathological damages were much milder in group T than those in group P under microscope. Conclusions P38MAPK plays an important role in the development of SAP. SB203580 can inhibit P38MAPK activity, decrease inflammatory mediator levels, increase the apoptosis rate of pancreatic acinar cell and reduce the pathological damage of the pancreas.
