益活清胰汤对重症急性胰腺炎大鼠海马CAI区嗜碱性成纤维细胞生长因子的影响

[目的]探讨益活清胰汤对大鼠重症急性胰腺炎(SAP)并发胰性脑病(PE)海马CAI区嗜碱性成纤维细胞生长因子(bFGF)的影响.[方法]45只SD大鼠建立SAP模型,随机分为益活清胰汤(C)组、造模(B)组、假手术(A)组,测定6、12、24 h各时点血浆肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、磷脂酶A2(PLA)值.对大脑皮层和海马组织形态、bFGF的表达进行观察.[结果]B、C两组术后6 h TNF-α、IL-6、PLA2开始升高,24 h达高峰.C组6、12、24 h各时点的TNF-α、IL-6、PLA2值小于A组(P＜0.01).海马bFGF表达显著增多.[结论]益活清胰汤能降低SAP血浆TNF-α、IL-6及PLA2水平,改善脑血流量,对抗缺血低氧,增强SAP时海马组织bFGF的合成、分泌,阻止神经细胞凋亡和(或)促进新的神经元出芽及突触形成.     

重组葡激酶对重症急性胰腺炎大鼠心肌损伤的治疗作用

[目的]研究重组葡激酶(r-Sak)对大鼠重症急性胰腺炎(SAP)的发展及心肌损伤的干预作用,探讨其作用机制.[方法]63只SD大鼠随机分为假手术(A)组(n=9),模型对照(B)组(n=27),r-Sak治疗(C)组(n=27).SAP模型采用5%牛磺胆酸钠胰胆管逆行注射方法建立.ELISA法测定6、12、18 h各时点血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、肌酸激酶同工酶(CK-MB)及心肌肌钙蛋白(CTn1)水平,免疫组化法检测术后6、12、18 h各时点心肌核转录因子-κB(NF-κB)的活化情况,光镜及电镜下观察胰腺及心肌组织的病理变化.[结果]大鼠从术后6 h开始出现CTn1、CK-MB升高,治疗组各时点较对照组明显下降(P＜0.05).IL-6、TNF-α水平亦从术后6 h开始升高,其变化在时点上与CTn1、CK-MB的变化具有一致性,治疗组各时点与对照组相比明显下降(P＜0.05).治疗组胰腺及心肌组织的出血坏死减轻,微血管血栓的形成减少.[结论]r-Sak能减轻SAP的病变程度和心肌损伤,可能具有治疗SAP及预防心肌损伤等并发症的作用,特异性溶栓剂的应用可能成为治疗SAP的新途径.     

益活清胰Ⅰ号对重症急性胰腺炎大鼠心肌组织中细胞凋亡调节蛋白表达的影响

[目的]研究益活清胰Ⅰ号对重症急性胰腺炎(SAP)大鼠心肌功能损害时细胞凋亡调节蛋白Bcl-2和Bax在心肌组织中表达的影响,并探讨其作用的机制.[方法]84只SD大鼠随机分为假手术组(正常组,n=12)、对照组(n=36)及治疗组(n=36).SAP模型采用5%的牛磺胆酸钠胰胆管逆行注射方法建立.苏木精-伊红染色光镜下观察胰腺及心肌组织的病理变化,免疫组化法检测术后6、12、18 h心肌Bcl-2、Bax表达及核因子-κB(NF-κB)活化情况.[结果]治疗组胰腺及心肌组织的病理变化减轻,SAP各时间点均可见NF-κB明显活化,治疗组各时间点NF-κB活化与对照组相比均明显减弱(P＜0.01).术后6 h各组Bcl-2、Bax无显著性变化(P＞0.05),12、18 h对照组Bcl-2的表达较正常组及治疗组显著减少(P＜0.01),12、18 h对照组Bax的表达较正常组及治疗组显著增加(P＜0.01).[结论]益活清胰Ⅰ号可减轻NF-κB在心肌组织中的活化,减少SAP大鼠心肌组织Bax的表达及增强Bcl-2的表达,从而减轻心肌细胞凋亡,对SAP心肌组织具有保护作用.     

益活清胰汤对大鼠重症急性胰腺炎心肌损伤的影响

[目的]研究益活清胰汤对大鼠重症急性胰腺炎(SAP)心肌损伤的影响.[方法]45只SD大鼠建立SAP模型,随机分为治疗组、对照组、正常组,测定6、12、24 h血淀粉酶(AMY)、脂肪酶(CIP)、肌酸激酶同工酶(CIK-MB)、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、心肌肌钙蛋白(CTn1).[结果]术后6 h大鼠心电图T波、ST段均有异常改变,血AMY、CIP、CK-MB、TNF-α、IL-6、CTn1呈进行性升高.治疗组用药后ECG T波、ST段下移,与对照组相比P＜0.01;血AMY、LIP、CK-MB、TNF-α、IL-6、CTn1明显下降,与对照组相比P＜0.01.[结论]TNF-α、IL-6可能是介导SAP心脏功能障碍的重要递质,监测TNF-α、IL-6、CTn1可能有预防SAP心肌损伤的作用,益活清胰汤能降低TNF-α、IL-6的表达,是治疗SAP心肌损伤较为理想的药物.     

胰炎灵颗粒剂对重症急性胰腺炎大鼠血清TNF、IL-6和IL-8水平的影响

将125只Wistar大鼠随机分为6组,A、C、D、E、F组各20只,B组25只.A组为假手术组,其余各组均于胰胆管逆行注射5%牛磺胆酸钠建立大鼠重症急性胰腺炎(SAP)模型.各组均于造模后即刻及12 h进行下列处理:C组腹腔注射抑肽酶注射液23 300 U/kg;D、E、F组分别予0.75、 0.37、0.19 g/ml胰炎灵颗粒剂混悬液灌胃;A、B组均予等容量生理盐水灌胃.诱发SAP模型后24 h测定各组血清TNF-α、IL-6、IL-8水平.结果 B、C、D、E、F 组血清TNF-α、IL-6、IL-8水平均明显升高;但C、D、E、F 组明显低于B组(P＜0.05).证实胰炎灵颗粒剂能调节细胞因子代谢,促进SAP恢复.     

重组葡激酶加中药对重症急性胰腺炎大鼠心肌核转录因子кВ的激活作用

[目的]研究重症急性胰腺炎(SAP)心肌功能损害时心肌核转录因子кВ(NF-кВ)的活化及葡激酶的干预作用.[方法]63只SD大鼠随机分为假手术组(n=9)、对照组(n=27)、葡激酶合用益活清胰汤治疗组(n=27),SAP模型采用5%牛磺胆酸钠胰胆管逆行注射方法建立.ELISA法测定6、12、24 h各时点血肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平,RT-PCR检测心肌NF-кВ mRNA的表达,免疫组化法检测心肌NF-кВ蛋白的表达,苏木精-伊红染色光镜下观察胰腺及心肌组织的病理变化.[结果]术后6 h大鼠心肌NF-кΒmRNA及其蛋白表达异常增高,TNF-α、IL-6呈进行性升高,治疗组用药后心肌NF-кВmRNA及蛋白表达下调,血TNF-α、IL-6明显下降,与对照组相比P＜0.05,治疗组胰腺及心肌组织的病理变化减轻.[结论]SAP大鼠心肌损伤可能与循环中TNF-α、IL-6水平升高导致的心肌NF-кВ活化有关,益活清胰汤合用葡激酶对SAP并发的心肌损伤具有防治作用.     

骨髓间充质干细胞在胰腺生理更新和病理再生中的作用

目的:探讨骨髓间充质干细胞在胰腺生理更新和病理再生中的作用. 方法:将60只SD大鼠随机分为5组,每组12 只．A组为正常阴性对照组,不作任何处理,B 组为自体骨髓回输对照组,C组为雨蛙肽致轻度胰腺炎(MAP)模型组,D组为L-精氨酸致重度胰腺炎(SAP)模型组,E组为粒细胞集落因子(G-CSF)预处理组(SAP GSF):在造模前3 d,sc G-CSF 40μg(kg·d),共3 d,其余处理同 D组．造模前3 d用核染料Hoechst33258标记自体骨髓间充质干细胞(MSC),并回输到自体骨髓腔．于骨髓干细胞回输后的2 wk和8 wk,分批处死大鼠,采集胰腺,立即进行冰冻切片, 荧光显微镜下直接观察胰腺组织中是否有呈现黄绿色荧光的细胞,选择有上述黄绿色荧光的冰冻切片进行免疫荧光染色,观察有无 Cytokeratin 19、胰岛素和胰高血糖素染色呈阳性的细胞．结果:A组的胰腺冰冻切片未见有黄绿色荧光．造模后2 wk,B、C、E和D组存活大鼠可见标记的MSC出现在正常胰腺组织和损伤胰腺组织中,在正常胰腺组织中偶见,而在损伤胰腺组织中多见,尤以GSF预处理组最多见, C、D、E组一直持续到8 wk仍可见到黄绿色荧光．A和D组死亡大鼠未见Cytokeratin 19、胰岛素和胰高血糖素染色呈阳性的细胞．造模后2 wk,B、C、E和D组存活大鼠掺入损伤胰腺中的MSC均有分化为Cytokeratin 19染色阳性的细胞,未见胰岛素和胰高血糖素染色呈阳性的细胞．造模后8 wk,胰岛素和胰高血糖素染色呈阳性的细胞在C、D组偶见,E组散见．结论:自体骨髓间充质干细胞参与胰腺的生理更新和病理再生．     

愈疡散对胃溃疡大鼠血一氧化氮和内皮素的影响

[目的]探讨愈疡散对胃溃疡大鼠血一氧化氮(NO)和内皮素-1(ET-1)的影响.[方法]采用大鼠冰醋酸胃溃疡模型,设空白对照组(A组)、假手术组(B组)、西药对照组(C组)、愈疡散大、小剂量组(D、E组)、胃溃疡模型组(F组).A、B、F组均灌服0.85%氯化钠溶液;D、E组分别灌服愈疡散5.0g/kg体重、2.5g/kg体重;C组灌服雷尼替丁0.03g/kg体重.于治疗前后分别检测血NO及ET-1.实验结束后,用苏木精-伊红染色对大鼠再生胃黏膜厚度、上皮细胞/腺腔数比值进行观察.[结果]造模7 d,C、D、E、F组血清NO显著降低,血浆ET-1明显升高,与A、B组比较差异有统计学意义(P＜0.05).治疗28 d,D组血清NO显著升高,而血浆ET-1明显降低,与F、E组比较均P＜0.05.再生胃黏膜厚度:D、E、C组明显高于F组(P＜0.05),D、E组与A、B组比较均P＜0.05.上皮细胞/腺腔数比值:A、B组与C、F组,D组与C、F组之间均P＜0.05.[结论]愈疡散促进溃疡愈合,增加胃黏膜的防御能力,提高再生黏膜功能成熟度,可能与其诱导、促进NO合成,反馈性地抑制ET-1释放,维持NO和ET-1的动态平衡有关.     

姜黄素在大鼠重症急性胰腺炎中的研究

目的观察姜黄素对大鼠重症急性胰腺炎(SAP)NF-κB p65蛋白的表达水平,血清淀粉酶、细胞因子及胰腺组织的改变,探讨姜黄素对大鼠重症急性胰腺炎防治的作用。方法通过牛磺胆酸钠诱导大鼠重症急性胰腺炎模型,将54只SD大鼠随机分成3组:假手术对照组(N组)18只,重症急性胰腺炎模型组(M组)18只,姜黄素干预组(C组)18只。3组分别于3h、6h、12h等3个时间点取腹水、血清及胰腺组织。采用全自动生化分析仪检测各组血清淀粉酶(AMY)水平。采用ELISA检测各组血清IL-6和TNF-α的水平。采用HE染色观察胰腺的病理学损伤和评分及免疫组化染色测定NF-κBp65蛋白的表达。结果 M组血清AMY较N组明显升高(P<0.0001);C组血清AMY水平较M组有所下降(P<0.05)。C组的水肿、炎症浸润、出血和Schmidt评分均较M组降低(P<0.05)。M组大鼠各时间点的胰腺组织NFκb的阳性表达水平较N组和C组明显增加(P<0.05),C组各时间点胰腺组织NFκB p65蛋白的阳性表达较M组有所下降(P<0.05)。M组血清IL-6、TNF-α水平比N组明显升高(P<0.05),C组工IL-6、TNF-α水平较M组明显下降(P<0.05)。结论姜黄素能在一定程度上抑制NF-κB信号通路的激活并减轻SAP的病理损伤,从而起到防治作用。     

吡咯烷二硫代氨基甲酸盐对大鼠急性坏死性胰腺炎肝损伤的保护作用

目的:探讨核因子KB(NF-κB)抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)对大鼠急性坏死性胰腺炎(ANP)的预防治疗作用。方法:大鼠80只随机分为正常对照组(Z)、胰腺炎组(Y)和干预纽.干预组又分为建模前1h PDTC干预组(A)、建模后1h PDTC干预组(B)和建模后6h干预组(C).干预组按不同时间ip PDTC.建模后6,12,24 h分批处死,临床全自动生化仪检测血清谷丙转氨酶(ALT)和淀粉酶(AMY),用凝胶迁移率改变分析法(EMSA)测定胰腺和肝脏中NF-κB的活性.同时观察胰腺和肝脏的病理改变.结果:正常大鼠组织中几乎测不到NF-κB的活性,与Z组比较,Y组胰腺和肝脏组织中6,12,24 h NF-κB活性分别明显增加(P<0.001).建模前1h,1h后使用PDTC,胰腺和肝脏组织中NF-κB活性均受到抑制(18.14±3.30,23.79±3.62 vs 24.82±4.57:10.68±2.51,13.83±2.70 vs 16.38±2.50;P<0.05),Y组血清ALT,AMY均高于对照组.病理学检查可以见到Y组和A,B,C组的胰腺和肝脏均有炎性改变,但A组较Y组明显为轻.结论:NF-κB的异常活化与SAP以及肝损伤有明显关系:PDTC对SAP时肝损伤的发生有一定的预防作用.     

重组葡激酶加中药对重症急性胰腺炎大鼠心肌核转录因子κB的激活作用

[目的]研究重症急性胰腺炎（SAP）心肌功能损害时心肌核转录因子κB（NF-κB）的活化及葡激酶的干预作用。[方法]63只SD大鼠随机分为假手术组（n=9）、对照组（n=27）、葡激酶合用益活清胰汤治疗组（n=27），SAP模型采用5％牛磺胆酸钠胰胆管逆行注射方法建立。ELISA法测定6、12、24h各时点血肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）水平，RT-PCR检测心肌NF-κB mRNA的表达，免疫组化法检测心肌NF-κB蛋白的表达，苏木精-伊红染色光镜下观察胰腺及心肌组织的病理变化。[结果]术后6h大鼠心肌NF-κB mRNA及其蛋白表达异常增高，TNF-α、IL-6呈进行性升高，治疗组用药后心肌NF-κB mRNA及蛋白表达下调，血TNF-α、IL-6明显下降，与对照组相比P＜0．05，治疗组胰腺及心肌组织的病理变化减轻。[结论]SAP大鼠心肌损伤可能与循环中TNF-α、IL-6水平升高导致的心肌NF-κB活化有关，益活清胰汤合用葡激酶对SAP并发的心肌损伤具有防治作用。     

氨基胍和泰能对急性坏死性胰腺炎肠道细菌易位的影响

目的 观察氨基胍和泰能对ANP大鼠肠道细菌易位的影响,探讨其防治胰腺感染的效果.方法 50只SD大鼠随机数字法分为对照组、ANP组、氨基胍组、泰能组和氨基胍+泰能组(联合组),各10只.采用胰腺实质均匀注射5%牛黄胆酸钠的方法制作ANP模型,氨基胍组于制模后30min腹腔注射氨基胍100 mg/kg体重;泰能组于制模后6 h腹腔注射泰能60 mg/kg体重;联合组注射2种药.制模后48 h处死大鼠,检测血清淀粉酶和D-乳酸、胰腺组织MPO水平,观察胰腺病理变化,采集胰腺、肝脏、血液、肠系膜淋巴结、腹水行细菌培养.结果 (1)氨基胍组和联合组血清淀粉酶分别为(1173.30±199.73)U/L、(1075.00±200.40)U/L,血清D-乳酸分别为(7.17±1.25)μg/ml、(6.98±1.06)μg/ml,胰腺MPO分别为(0.80±0.07)U/g湿片、(0.78±0.08)U/g湿片,细菌培养平均阳性率分别为20%、16%.较ANP组血清淀粉酶(2234.60±692.06)U/L、血清D-乳酸(12.41±1.78)μg/ml、胰腺MPO(1.59±0.20)U/g湿片、细菌培养平均阳性率60%均有显著改善(P＜0.05);(2)泰能组胰腺MPO为(0.80±0.06)U/g湿片、细菌培养平均阳性率为18%,也较ANP组显著改善(P＜0.05).但泰能组的血清淀粉酶和D-乳酸与ANP组比较无统计学差异;(3)ANP组胰腺实质有片状坏死、间质充血、大量白细胞浸润,而氨基胍组、泰能组、联合组胰腺组织无明显白细胞浸润.结论 氨基胍和泰能能减少ANP大鼠肠道细菌易位,减少SAP胰腺继发感染.     

Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis

AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n = 21) received no treatment after the SAP model was established; group B (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0,5 h before the SAP model was established; group C (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the ex- pression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r=-0.748, -0.827, -0.723; P＜0.01). In the second series of experiments, no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model (P＜0.01, P＜0.05), but the expression of MCP was not influenced (P＞0.05). The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model (P＜0.05), but the expression of CD59 and MCP did not change (P＞0.05). CONCLUSION: Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.     

重症急性胰腺炎大鼠并发肠黏膜屏障功能障碍

目的探讨重症急性胰腺炎(SAP)大鼠肠黏膜屏障功能的状况。方法 48只SD大鼠,随机分两组:假手术组(A组,n=24)、SAP模型组(B组,n=24)。用3%牛磺胆酸钠制备SAP大鼠模型。麻醉苏醒,即开始灌胃,6h/次,A、B组用灌胃器按1 mL/100 g/次生理盐水灌胃。制模后各组在6、12、24 h 3个时间点取材;开腹后观察腹水量及其颜色,观察胃肠道大体情况;取血用酶联免疫吸附双抗夹心法检测血清二胺氧化酶(DAO)及D-乳酸浓度;取胰腺及回肠末段组织做病理检查,并进行胰腺病理组织评分;取回肠末段部分组织做扫描电镜检查。结果A组无腹水;B组腹水多,肠道明显扩张,积液积气,部分肠管发黑。B组血清DAO、D-乳酸的浓度较A组升高(P<0.01)。B组胰腺及回肠病理损害重,胰腺病理组织评分较A组高(P<0.05);扫描电镜检查A组基本正常,B组损伤重。结论 SAP大鼠并发肠黏膜屏障功能障碍。     

An experimental study of emodin assisted early enteral nutrition for the treatment of severe acute pancreatitis

BACKGROUND/AIMS: Both emodin and early enteral nutrition (EEN) have been affirmed as effective means to restore the intestinal mucosal function and abate the severity of severe acute pancreatitis (SAP). However, whether a combined strategy applying both is more effective than either one alone is still undetermined. In this study, we investigated the feasibility and efficacy of emodin assisted early enteral nutrition (EAEEN) for the treatment of SAP. METHODOLOGY: Sixty male Wistar rats were randomly divided into four groups (n=15). SAP was induced in all the rats by a retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct. Rats in group A received no further intervention, group B with emodin alone, group C with early enteral nutrition (EEN) alone, and group D with emodin assisted early enteral nutrition (EAEEN), respectively, all through an enteral nutrition tube incubated after the induction of SAP. 72 hours after SAP induction, all surviving animals were sacrificed to collect blood and tissue samples for the following measurements: serum amylase, tumor necrosis factor-alpha (TNF-alpha), angiotensin II (AngII) and maleic dialdehyde (MDA), intestinal mucosal secretory IgA (SIgA), pancreatic myeloper oxidase (MPO) activity, and the wet-dry weight ratio of pancreatic tissue (pww/dw). The severity of pancreatic destruction was analyzed by pathological grading and scoring. The severity of intestinal mucosal damage was assessed by the wet-dry weight ratio of ileum (iww/dw), plasma D-lactate and plasma endotoxin. RESULTS: The results of every index in group B, C and D were significantly better than those in group A (P<0.05). Compared with group B and C, group D had significantly reduced levels of serum amylase, TNF-alpha, Ang-II and MDA (P<0.05). Group D also had significantly lowered plasma D-lactate and endotoxin, and decreased pancreatic MPO activity (P<0.05). The pww/dw and iww/dw ratios were decreased, while the SIgA level increased in this group, both with statistical significance (P<0.05). Furthermore, group D had significantly better pancreatic pathologic scores over group B and group C (P<0.05). CONCLUSIONS: Our results suggested that EAEEN could obviously abate the severity of experimental SAP in rats. This combined strategy was rational, safe and more effective than either EEN or emodin used alone, and has a broad potential for future clinical application.     

生长激素对实验性急性坏死性胰腺炎肠道细菌移居的影响

目的 探讨生长激素（ｇｒｏｗｔｈ ｈｏｒｍｏｎｅ,ＧＨ）对急性坏死性胰腺炎（ａｃｕｔｅ ｍｅｃｒｏｔｉｚｉｎｇｐａｎｃｒｅａｔｉｔｉｓ,ＡＮＰ）肠道细菌移居的 影响。方法 采用胆胰管内逆行注射５％牛碘胆酸钠溶液诱导大鼠ＡＮＰ模型。１３７只在鼠随机分成３组：假手术组（ｎ＝４１）、ＡＮＰ＋ＮＳ组（ｎ＝４８）和ＮＡＰ＋ＧＨ组（ｎ＝４８）。ＧＨ治疗组大鼠皮下注射０．７５Ｕ／ｋｇ体重基因重组ＧＨ。观察血清淀     

抗氧化剂对大鼠重症急性胰腺炎胰腺腺泡细胞凋亡的影响

目的探讨四氢化吡咯二硫代氨基甲酸酯（PDTC）对重症急性胰腺炎（SAP）胰腺腺泡细胞凋亡的影响。方法SD大鼠72只，随机分为：假手术组（sham operation，SO）、SAP组和PDTC组。SAP模型采用5％牛磺胆酸钠1ml/kg胰胆管逆行穿刺注射建立，PDTC组在造模前1h给予腹腔注射PDTC（1130mg/kg），术后分4个时段（1、3、6、12h）分批进行腹主动脉采血后处死，取胰腺组织作病理切片与液氮冻存。胰腺腺泡细胞的凋亡检测应用TUNEL法、电镜以及免疫组化法检测胰腺组织Caspase-3的表达；核因子（NF）-κB活化的检测应用免疫组化法。同时观察各组血清淀粉酶、脂肪酶水平及胰腺组织病理学评分。结果SAP组各时间点血清淀粉酶及脂肪酶水平及胰腺组织病理组织学评分较SO组显著增高（P〈0．05）。PDTC治疗组血清淀粉酶、脂肪酶水平较SAP组明显降低；胰腺组织病理组织学评分明显改善。PDTC治疗后3、6、12h胰腺组织Caspase-3的表达显著高于SAP组（P〈0．01），而在1h无统计学差异；各时间点胰腺腺泡细胞凋广指数显著高于SAP组（P〈0．01）；NF—κB的活化显著低于SAP组（P〈0．01）。结论SAP时，PDTC可能通过抑制NF—κB的活化，从而抑制NF—κB介导胰腺细胞的抗凋亡效应，减少胰腺腺泡细胞坏死。     

Thymosin alpha 1 improves severe acute pancreatitis in rats via regulation of peripheral T cell number and cytokine serum level

AIM: The aim of this study was to investigate the effect of thymosin alpha 1 (TA1) on severe acute pancreatitis (SAP) in rats. METHODS: Healthy Sprague-Dawley rats (n = 72) were randomly divided into four groups: control group, SAP group, and two TA1 treated groups. SAP was induced by injection of 5% sterile sodium taurocholate into the biliopancreatic duct (BPD), after which TA1 was given subcutaneously at 0 and 2 h at a dose of 100 microg/kg. The rats were killed at 3, 6 and 12 h, respectively. Serum amylase and lipase, interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), pancreatic wet/dry weight ratio and the percentage of CD3/CD4+/CD8+ T cells in peripheral blood mononuclear cells (PBMC) were measured. Next, 30 rats were randomly divided into three groups (each group containing 10 animals): SAP group (S) and two TA1 treated groups. The effects of TA1 on the survival of SAP were assessed 72 h after the induction of SAP. RESULTS: There was no significant change in the serum amylase and lipase levels after TA1 administration. Levels of serum IL-1beta, TNF-alpha and pancreatic wet/dry weight ratio were significantly reduced after TA1-treatment. Application of TA1 significantly balanced CD3/CD4+/CD8+ T cells of PBMC and improved histological scores and the survival rate. CONCLUSION: TA1 can reduce pancreatic inflammation by regulating differentiation of CD3/CD4+ T cells and decreasing the release of cytokines, thus attenuates pancreatic severity in SAP rats.     

罗格列酮对大鼠重症急性胰腺炎NF-κB和ICAM-1的作用

目的探讨大鼠重症急性胰腺炎（SAP）时罗格列酮对核因子-κB（NF-κB）和细胞间黏附分子-1（ICAM-1）的作用。方法急性胰腺炎模型组（SAP组）逆行胆胰管注射牛磺胆酸钠建立大鼠SAP模型;假手术组（SO组）逆行胆胰管注射等量生理盐水;罗格列酮组（R组）于造模前30min给予罗格列酮。检测血清淀粉酶（AMY）的变化,取胰头部胰腺组织行病理学检查;免疫组化检测胰腺组织NF-κB和ICAM-1的表达情况。结果SAP组各时间点AMY、胰腺组织病理评分及NF-κB和ICAM-1的表达较SO组增高（P〈0．01）;R组各时间点上述指标较SAP组均下降,但仍高于SO组（P〈0．01）;NF-κB和ICAM-1两者在SAP组和R组具有相关性（P〈0．01）。结论罗格列酮能减轻大鼠SAP胰腺病理损伤,其机制可能与通过抑制NF-κB的活性、降低ICAM-1的表达有关。     

白细胞介素-18在实验性重症急性胰腺炎肝损伤中的作用

自细胞介素（IL）-18是一种新发现的促炎细胞因子，其血清水平与重症急性胰腺炎（SAP）合并肝损伤明显相关，然而关于其在SAP急性损伤肝组织中的变化和意义鲜有报道。目的：研究IL-18在SAP大鼠肝组织中的表达．探讨IL-18在SAP肝损伤中的作用。方法：以4％牛磺胆酸钠胰胆管逆行注射诱导大鼠SAP模型。32只大鼠随机分为对照组和SAP6h、12h、18h组。动态测定血清淀粉酶、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平和腹水量；光学显微镜下观察胰腺和肝组织损伤情况；以免疫组化方法检测IL-18在肝组织中的表达和定位：以蛋白质印迹法检测肝组织中IL-18前体和成熟IL-18的表达。结果：SAP组各时间点血清淀粉酶、ALT、AST水平均明显升高，腹水量增多，与对照组相比差异有统计学意义（P〈0．01），与胰腺和肝脏的组织病理学改变相一致。造模后IL-18在肝脏Kupffer细胞胞质中呈强阳性表达，阳性Kupffer细胞数增多，成熟IL-18表达明显增加，各时间点与对照组相比差异均有统计学意义，以12h组为著（P〈0．01）。结论：Kupffer细胞是肝脏成熟IL-18的主要来源．成熟IL-18表达上调可能在SAP早期肝损伤中发挥重要作用。