胰瘅1号、胰瘅2号、胰瘅贴对重症急性胰腺炎模型大鼠TLR4/NF-κB信号通路抑制效应

目的：应用胰瘅1号、胰瘅2号、胰瘅贴综合治疗重症急性胰腺炎（severe acute pancreatitis,SAP）大鼠,探讨其对SAP大鼠TLR4/NF-κB信号传导通路的抑制效应及机制。方法：建立SAP动物模型,将其分为假手术组（J组）,模型组（M组）,善宁组（S组）,胰瘅1号、胰瘅2号、胰瘅贴组（Y组）,善宁、胰瘅1号、胰瘅2号、胰瘅贴组（Z组）。计算3h、12h、72h、2w的血清淀粉酶（AMY）、肿瘤坏死因子（TNF-α）、白介素-1β（IL-1β）、Toll样受体4（TLR4）、核因子-κB（NF-κB）、胰腺组织大体形态和光镜下改变。结果：随着时间的推移,Z组胰腺组织形态变化明显减轻,胰腺组织病理评分低于M组、S组、Y组;随着时间的推移,Z组血清AMY数值、TNF-α、IL-1β、TLR4、NF-κB活性低于M组、S组、Y组。结论：胰瘅1号、胰瘅2号、胰瘅贴综合治疗SAP大鼠能明显减轻胰腺小叶间弥漫性水肿、炎症,胰腺实质性出血、腺管点状坏死灶、小叶缺失;其作用机制可能是通过抑制胰腺组织TLR4/NF-κB信号通路中TLR4和NF-κB的活性,减少下游炎症介质（TNF-α和IL-1β）的释放,阻断SIRS和MODS的发生或减轻其严重程度,从而达到有效治疗SAP的目的。

THE INHIBITORY EFFECT OF YIDAN 1 ,YIDAN 2 AND YIDAN PLASTER ON TLR4/NF-κB SIGNALING IN SEVERE ACUTE PANCREATITIS RAT AND ITS MACHANISM

Objective：To study the effect of Yidan preparations on TLR4/NF-κB signaling in severe acute pancreatitis rats and its possible mechanism.Methods：Estabilished rat models of SAP were randomly divided into sham operation group（J group）,severe acute panreatitis group（M group）,somatostatin group（S group）,Yidan 1,Yidan 2,Yidan Plaster group（Y group）,and Yidan combined with somatostatin group（Z group）.The pancreatic injury was compared through light microscope;AMY,TNF-α and IL-1β were detected by ELISA;TLR4 and NF-κB in pancreatic tissues were semiquantitatively detected by immunohistochemical method at 3h,12h,72h,2w.Results： The morphologic change of Z group in pancreatic tissue obviously alleviated.The pathological score of Z group was lower than that of M group,S group and Y group at different time（P〈0.01）;the level of AMY,TNF-α,IL-1β in blood serum of Z group at different time was lower than that of M group,S group and Y group（P〈0.01）.The activity variance of TLR4,NF-κB of Z group at different time was lower than that of M group,S group and Y group（P〈0.01）.Conclusion： Yidan prepararions combined modality therapy of SAP rats can obviously alleviate pancreatic lobulus diffuse edema,inflammation,substantial hemorrhage,tubular necrosis spots,and leaflets missing（P〈0.05）;the mechanism may be involved with the inhibition of the activity of TLR4 and NF-κB in pancreatic tissue,reducing liberation of downstream inflammatory mediators（TNF-α and IL-1β）,and thus preventing or reducing the occurrence of SIRS and MODS to achieve therapeutic purposes.