摘要
目的研究全程运用大承气汤加味方对重症急性胰腺炎（severe acute pancreatitis,SAP）模型大鼠炎症介质的影响,以明确全程运用大承气汤加味方通腑导滞较单纯早期运用对SAP肠黏膜屏障损伤的干预优势。方法采用随机数字表法将190只SD大鼠分为假手术组、模型组、奥曲肽组（octreotide,OT组）、早期大承气汤加味方组（早期组）及全程大承气汤加味方组（全程组）,每组38只。采用肠壁穿刺逆行胰胆管注射5%牛黄胆酸钠建立SAP模型。造模3 h后假手术组及模型组灌胃生理盐水,每12 h 1次,OT组皮下注射OT 1.35μg/100 g,每8 h 1次;早期组灌胃大承气汤加味方0.4 mL/100 g,6 h后改为生理盐水,每12h 1次;全程组灌胃大承气汤加味方0.4 mL/100 g,每12 h 1次。造模后48 h观察各组累积生存率及胰腺、小肠光学显微镜下表现;分别于造模4、6、24、48 h进行胰腺及小肠组织病理评分并检测血清淀粉酶（amylase,AMY）、ALT及TNF-α水平;采用Western blot法测定小肠组织高迁移率族蛋白B1（high mobility group box protein 1,HMGB1）表达水平;造模48 h观察各组肠系膜淋巴结（mesenteric lymph nodes,MLNs）细菌移位阳性率,对血清TNF-α、小肠组织HMGB1与胰腺、小肠组织病理评分的相关性进行分析。结果各组累积生存率分别为假手术组100.0%、全程组79.2%、OT组70.8%、早期组45.8%及模型组37.5%。造模6 h后,与模型组比较,全程组、早期组及OT组胰腺及小肠组织病理评分降低（P〈0.05）,造模24、48 h,全程组、OT组胰腺及小肠组织病理评分明显低于早期组（P〈0.05）。造模6、24、48 h,与模型组比较,全程组、早期组及OT组血清AMY、ALT均降低（P〈0.05）;造模48 h,全程组及OT组血清AMY、ALT均低于早期组（P〈0.05）。造模6 h,全程组、早期组及OT组血清TNF-α低于模型组（P〈0.05）。造模6、24、48 h,此3组小肠组织HMGB1水平亦低于模型组（P〈0.05）,其中24、48 h全程组及OT组均低于早期组（P〈0.05）。造模48 h,全程组、OT组MLNs细菌移位阳性数低于模型组及早期组（P〈0.05）。SAP早期6 h内血清TNF-α与胰腺病理评分呈正相关（r=0.579,P〈0.01）。ROC曲线分析提示血清TNF-α水平可预测SAP严重程度（ROC曲线下面积为0.990,95%CI：0.971~1.000）。小肠组织HMGB1水平与小肠组织病理评分呈正相关（r=0.620,P〈0.01）。结论早期运用大承气汤加味方通腑导滞能有效降低炎症因子TNF-α的释放,而全程运用大承气汤加味方通腑导滞能有效抑制HMGB1表达,较单纯早期治疗能更好地减轻胰腺及小肠损伤,降低MLNs移位阳性率,提高生存率。
Objective To study the effect of Modified Dachengqi Decoction（ MDD） as whole course therapy on mediators of inflammation in severe acute pancreatitis（ SAP） model rats,and to compare interventional advantages over intestinal mucosal barrier（ IMB） of SAP rats between whole course therapy of MDD and early stage therapy of MDD. Methods Totally190 SD rats were divided into five groups according to random digit table,i. e.,the sham-operation group,the model group,the octreotide（ OT） group,the early stage MDD treatment group,the whole course MDD treatment group,38 in each group.SAP models were established with retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct. Three hours after modeling normal saline（ NS） was administered to rats in the sham-operation group and the model group by gastrogavage,once per 12 h. 1. 35 μg /100 g OT was subcutaneously injected to rats in the OT group,once every 8 h. 0. 4 mL /100 g MDD was administered to rats in the early stage MDD treatment group,and 6 h later changed to NS（ once per 12 h）. 0. 4 mL /100 g MDD was administered to rats in the whole course MDD treatment group,once every 12 h. The accumulative survival rate and morphological manifestations of pancreas and small intestine were observed under microscope 48 h after modeling. Pathologic scores of the pancreas and small intestine were conducted at 4,6,24,and 48 h after modeling. Contents of serum amylase（ AMY）,alanine transaminase（ ALT）,and TNF-α were also detected. The expression of high mobility group box protein 1（ HMGB1） in the small intestine tissue was also detected by Western blot. The positive rate of bacterial translocation in mesenteric lymph nodes（ MLNs） was observed within 48 h. Correlations between serum TNF-α or HMGB1 in small intestinal tissue and pathological scores of the pancreas or the small intestine were analyzed. Results The accumulative survival rate was100. 0% in the sham-operation group,79. 2% in the whole course MDD treatment group,70. 8% in the OT group,45. 8% in the early stage MDD treatment group,and 37. 5% in the model group. At 6 h after modeling,pathological scores decreased more in the whole course MDD treatment group,the early stage MDD treatment group,the OT group than in the model group（P〈0. 05）. At 24 and 48 h after modeling,pathological scores of the pancreas and the small intestine decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group（P〈0. 05）. At 6,24,and48 h after modeling,serum contents of AMY and ALT both decreased more in the whole course MDD treatment group,the early stage MDD treatment group,the OT group than in the model group（P〈0. 05）. At 48 h after modeling serum contents of AMY and ALT both decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group（P〈0. 05）. At 6 h after modeling serum TNF-α levels decreased more in the whole course MDD treatment group,the early stage MDD treatment group,the OT group than in the model group（P〈0. 05）. At 6,24,and 48 h after modeling the level of HMGB1 in the small intestinal tissue decreased more in the whole course MDD treatment group,the early stage MDD treatment group,the OT group than in the model group（P〈0. 05）. Of them,HMGB1 levels at 24 and 48 h were lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group（P〈0. 05）. The number of MLNs bacterial translocation at 48 h after modeling was lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group and the model group（P〈0. 05）. Serum TNF-α contents within 6 h were positively correlated with pathological scores of pancreas（r = 0. 579,P〈0. 01）. ROC curve showed that serum TNF-α contents could predict the severity of SAP（ ROC = 0. 990,95% CI： 0. 971 to 1. 000）. HMGB1 in the small intestine was positively correlated with pathological scores of the small intestine（r = 0. 620,P〈0. 01）. Conclusions Early stage use of MDD could effectively reduce the release of TNF-α,while whole course use of MDD could effectively inhibit the expression of HMGB1. The latter could preferably attenuate injuries of the pancreas and the small intestine,lower MLNs bacterial translocation,and elevate the survival rate.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2015年第12期1482-1489,共8页
Chinese Journal of Integrated Traditional and Western Medicine
基金
2010年浙江省中医药科学研究基金计划项目(No.2010ZB117)
关键词
大承气汤加味方
重症急性胰腺炎
全程治疗
炎症介质
肠黏膜屏障
Modified Dachengqi Decoction
severe acute pancreatitis
whole course therapy
mediators of inflammation
intestinal mucosal barrier
