重症急性胰腺炎肠内营养治疗的大鼠模型

Establishment of a severe acute pancreatitis rat model for evaluating enteral nutrition therapy

目的旨在建立适用于研究重症急性胰腺炎(SAP)营养治疗的大鼠模型,为SAP肠内营养(EN)研究提供实验和理论依据。方法80只SD大鼠,体重(200±10)g,随机分为对照组(共20只,分6、12、24和48h4个时间点观察组,每个时间点组为5只)和ANP组(共60只,其中20只分6、12、24和48h4个时间点观察组,每个时间点组为5只;其余40只,用于观察死亡率)。采用胰腺被膜下均匀注射3.8%牛磺胆酸钠造模,比较对照组和ANP组4个时间点血清淀粉酶和胰腺病理变化,以及观察胰外脏器的损伤程度,统计ANP组死亡率的情况。结果ANP组各时间点血清淀粉酶高于对照组,差异有显著统计学意义(P<0.01)。血清淀粉酶在造模6h后就明显升高,12h后高达(8287±179)U/L,24h仍维持在很高的水平,48h下降为(3217±249)U/L。模型诱发后随着时间进展,胰腺病理损害呈渐进性进展,胰腺组织出现出血、坏死,胰外脏器也有不同程度的损伤。ANP组动物第1、2、3、4、5、6和7天的累计死亡率分别为0(0/40)、7.5%(3/40)、20.0%(8/40)、35.0%(14/40)、40.0(16/40)、47.5%(19/40)和52.5%(21/40)。结论采用胰被膜下均匀注射3.8%牛磺胆酸钠可成功建立ANP动物模型,重复性好,病情呈渐进性发展,与人类SAP的自然病程类似,适用于进行SAP肠内营养治疗,以及需较长时间观察的研究。

Objective To establish an experimental severe acute pancreatitis （SAP） rat model for evaluating enteral nutrition （EN） therapy. Methods 80 SD rats were randomized into sham- operated group （SO group） and SAP group. The SAP model was established by injecting 1 ml 3.8 sodium taurocholate beneath the pancreatic capsule. Twenty rats of SO group and 20 rats of SAP group were killed at 6, 12, 24 and 48 h after operation to determine serum amylase, histopathologic changes of the pancreas and injury to other organs. The remaining 40 SAP rats were used to calculate the mortality. Results In SAP group, serum amylase increased at 6 h after injection of 3. 8% sodium taurocholate, reached the peak value at 12 h, remained at a high level at 24 h, and began to decline at 48 h. There was significant difference in serum amylase conentration between model group and SO group. The HE staining results showed that there were pancreatic hemorrhage, necrosis and progressive impairment. Multiple exptrapancreatic organ injuries were found in rats with experimental SAP. The cumulative morality of SAP group at day 1, 2, 3, 4, 5, 6and 7was0（0/40）, 7.5^（3/40）, 20.0%（8/40）, 35. 0%（14/40）, 40. 0（16/40）, 47. 5%0（19/40） and 52. 5%0（21/40） respectively. Conclusions It is an effective way to establish the SAP rat model by injecting 3. 8% sodium taurocholate beneath the pancreatic capsule. The SAP model thus established has good reproducibility.As the model resembles the natural course of human SAP, it is suitable for enteral therapy study, longterm mechanism study, conversion study and other therapeutic studies.