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实验性急性坏死性胰腺炎:大鼠实质内注射牛磺胆酸钠模型的评估与特征分析

Experimental acute necrotising pancreatitis: evaluation and characterisation of a model of intraparenchymal injection of sodium taurocholate in rats.

作者信息

Paran H, Mayo A, Kidron D, Sivak G, Reshef T, Vider T, Ziv O, Freund U

机构信息

Department of Surgery A, Meir Hospital, affiliated with the Sackler School of Medicine, Tel-Aviv University, Kfar-Sava, Israel.

出版信息

Eur J Surg. 2000 Nov;166(11):894-8. doi: 10.1080/110241500447308.

DOI:10.1080/110241500447308
PMID:11097158
Abstract

OBJECTIVES

To evaluate a simple model that produces progressive dose dependent pancreatitis, by intraparenchymal injection of sodium taurocholate.

DESIGN

Open laboratory study.

SETTING

Teaching hospital, Israel.

MATERIALS

Forty eight Wistar rats.

INTERVENTIONS

Sodium taurocholate was injected, 0.3 ml/100 g body weight, in concentrations of 5% and 10% into the pancreatic parenchyma of 32 Wistar rats, resulting in two distinct groups of severity. In 16 sham controls, saline was injected into the pancreas in similar fashion. Blood samples were withdrawn before, and 6, 24, 48, and 72 hours after induction of pancreatitis.

RESULTS

Six hours after taurocholate injection, there was a sharp increase in the plasma activities of amylase, lipase, and lactate dehydrogenase (LDH). After 24 hours plasma activities of amylase and lipase decreased to near normal values while LDH remained slightly increased for 48 hours and decreased only after 72 hours. At 6 hours after the injection, interleukin-6 (IL-6) concentrations had increased slightly in the 5% group and decreased to the baseline values at 24 hours. In the 10% group, the increase in IL-6 values was significantly greater than in the 5% group (p = 0.04), and correlated well with severity of pancreatitis as defined by histology (p = 0.01) and mortality (p = 0.037). Twenty four hours after injection of taurocholate, morphological changes comprising diffuse necrosis of the pancreas, fat necrosis, and intestinal dilatation secondary to paralytic ileus were severe. Histopathological examination of the pancreas showed good correlation with the clinical findings and with mortality. No morphological changes were detected when saline was injected into the pancreas (sham control), and only mild rises of IL-6, lipase, amylase, and LDH activities were seen at 6 hours after injection. The mortality, after 10 days, was 80% in the 10% taurocholate group, 30% in the 5% taurocholate group, and 0 in the sham control group (p < 0.05).

CONCLUSION

The intraparenchymal injection of taurocholate is easy to perform and highly reproducible. The histopathological injury is dose-dependent, as is the mortality. We conclude that this model is valuable for the study of new treatments for pancreatitis.

摘要

目的

通过向胰腺实质内注射牛磺胆酸钠来评估一种可产生进行性剂量依赖性胰腺炎的简单模型。

设计

开放性实验室研究。

地点

以色列的教学医院。

材料

48只Wistar大鼠。

干预措施

将浓度为5%和10%的牛磺胆酸钠以0.3 ml/100 g体重的剂量注射到32只Wistar大鼠的胰腺实质内,从而形成两组不同严重程度的胰腺炎。对16只假手术对照组大鼠,以同样方式向胰腺注射生理盐水。在诱导胰腺炎前以及诱导后6、24、48和72小时采集血样。

结果

注射牛磺胆酸钠6小时后,淀粉酶、脂肪酶和乳酸脱氢酶(LDH)的血浆活性急剧升高。24小时后,淀粉酶和脂肪酶的血浆活性降至接近正常水平,而LDH在48小时内仍略有升高,仅在72小时后下降。注射后6小时,5%组白细胞介素-6(IL-6)浓度略有升高,24小时降至基线值。在10%组中,IL-6值的升高明显大于5%组(p = 0.04),并且与组织学定义的胰腺炎严重程度(p = 0.01)和死亡率(p = 0.037)密切相关。注射牛磺胆酸钠24小时后,出现包括胰腺弥漫性坏死、脂肪坏死以及继发于麻痹性肠梗阻的肠扩张等形态学改变,且较为严重。胰腺的组织病理学检查结果与临床发现及死亡率具有良好的相关性。向胰腺注射生理盐水(假手术对照组)时未检测到形态学改变,仅在注射后6小时观察到IL-6、脂肪酶、淀粉酶和LDH活性有轻微升高。10天后,10%牛磺胆酸钠组的死亡率为80%,5%牛磺胆酸钠组为30%,假手术对照组为0(p < 0.05)。

结论

向胰腺实质内注射牛磺胆酸钠操作简便且具有高度可重复性。组织病理学损伤和死亡率均呈剂量依赖性。我们得出结论,该模型对于胰腺炎新治疗方法的研究具有重要价值。

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