重症急性胰腺炎器官损伤与内皮素-1mRNA表达的关系及丹参的影响

Influence of Salviae Miltiorrhizae on endothelin-1 mRNA expression and organ injury in severe acute pancreatitis

目的探讨重症急性胰腺炎(SAP)内皮素-1(ET-1)mRNA表达对胰腺及肺、肾损伤的作用机制,观察丹参注射液对ET-1mRNA表达及病情转归的影响。方法将Wistar大鼠随机分为模型组(n=15)、丹参组(n=15)、对照组(n=15)。建立SAP模型后,丹参组动物立即肌肉注射丹参注射液(每日2ml/kg体重),每6h1次,共给药4次。对照组仅行假手术。各组动物在术后24h测血淀粉酶、ET-1和腹水量。使用原位杂交和图像分析检测胰、肺、肾ET-1mRNA的表达强度,并观察胰、肺、肾病理变化。结果模型组血中淀粉酶(2156.05±355.87)U/L和腹水量(9.87±2.34)ml显著高于丹参组(1439.21±332.99)U/L、(5.27±2.81)ml和对照组(215.67±37.27)U/L、0ml(P<0.01)。模型组血中ET-1(185.47±20.80)ng/L高于丹参组(164.27±18.53)ng/L和对照组(72.90±17.27)ng/L(P<0.05,P<0.01)。模型组胰、肺、肾中ET-1mRNA表达显著高于丹参组(P<0.01)。丹参组胰、肺、肾病理改变较模型组减轻。结论SAP时胰腺的ET-1mRNA高表达导致ET-1过度生成并可能继发引起肺、肾病理损害。丹参能抑制胰腺的ET-1mRNA的过度表达,减轻血管内液体丢失,改善血流动力学,从而对胰腺及肺、肾组织起保护作用。

Objective To investigate the influence of Salviae Miltiorrhizae on the expression of endothelin-1 （ET-1） mRNA in pancreas, lung and kidney in rats with severe acute pancreatitis （SAP）. Methods Wistar rats were randomly divided into 3 groups： model group （MG, n = 15）, herbal group （HG, n = 15） and sham operation group （SG, n = 15）. Severe acute pancreatitis was induced in MG and HG. Sham operation was only made in SG. Salviae Miltiorrhizae （2 ml/kg·d^-1） was intramuscularly injected immediately after SAP was induced in HG. Ascites and serum ET-1 and amylase （AMY） levels were determined. ET-1 mRNA expression in pancreas, lung and kidney was detected by in situ hybridization. The pathologic changes of pancreas, lung and kidney were observed 24 h after establishment of the model. Results Volume of ascites （9.87±2.34） ml and serum levels of AMY （2 156.05 ± 355.87） U/L in MG were remarkably higher than in HG （5.27 ± 2.81） ml, （ 1 439.21 ± 332.99） U/L and CG （0 ml, 215.67± 37.27） U/L （P〈0.01）.The serum levels of ET-1 in MG （185.47 ± 20.80） ng/L were higher than in HG （164.27± 18.53） ng/L and CG （72.90± 17.27） ng/L （P〈 0.05, P〈 0.01）. The expression of ET-1 mRNA in pancreas, lung and kidney in MG was significandy higher than in HG （ P 〈 0.01 ）. The pathologic changes of pancreas, lung and kidney in HG were milder than in MG. Conclusion Overexpression of ET-1 mRNA in SAP plays an important role in injury of pancreas, lung and kidney. Salviae Miltiorrhizae inhibits the expression of ET-1 mRNA and ameliorates the pancreas, lung and renal injury.