秋水仙碱对大鼠急性胰腺炎的作用及其机制研究

Effects of colchicine on acute pancreatitis in rat models and the underlying mechanisms

目的观察秋水仙碱对急性胰腺炎(AP)的作用,并探讨相关机制。方法将30只AP大鼠随机分为模型组、低剂量组和高剂量组,每组10只。另取10只大鼠仅开腹,翻动胰腺,关腹,不做其他处理,设为对照组。低、高剂量组分别舌下静脉注射秋水仙碱2、4 mg/kg,对照组、模型组均舌下静脉注射等体积0.1%二甲基亚砜溶液,1次/d,连续5 d。采用酶联免疫吸附试验检测血清炎症因子水平;苏木精-伊红染色观察胰腺组织病理变化;Western blotting检测胰腺组织肿瘤坏死因子受体-1(TNF-R1)、TNFR1相关的死亡区域蛋白(TRADD)、受体相互作用蛋白激酶1(RIP1)蛋白的表达。结果与对照组比较,模型组、低剂量组、高剂量组血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)、降钙素基因相关肽(CGRP)水平、病理评分及TNF-R1、TRADD、RIP1蛋白相对表达量升高(P<0.05);与模型组比较,低剂量组、高剂量组血清IL-6、TNF-α、MDA、CGRP水平、病理评分及TNF-R1、TRADD、RIP1蛋白相对表达量降低(P<0.05);与低剂量组比较,高剂量组血清IL-6、TNF-α、MDA、CGRP水平、病理评分及TNF-R1、TRADD、RIP1蛋白相对表达量降低(P<0.05)。与对照组比较,模型组、低剂量组、高剂量组血清SOD活性降低(P<0.05);与模型组比较,低剂量组、高剂量组血清SOD活性增强(P<0.05);与低剂量组比较,高剂量组血清SOD活性增强(P<0.05)。结论秋水仙碱可减轻AP大鼠炎症反应、氧化应激,改善微循环,推测其作用机制与抑制TNF-α/TNF-R1信号通路有关。

Objective To observe the effect of colchicine on acute pancreatitis(AP)and to explore the underlying mechanisms.Methods Thirty AP rat models were randomly divided into model group,experimental-L group,and experimental-H group,with 10 rats in each group.Another 10 rats were sham-operated and set as the control group.The rats in the experimental-L group and the experimental-H group were injected sublingually with colchicine at doses of 2 and 4 mg/kg,respectively,while those in the control group and the model group were injected with the same amount of 0.1%dimethyl sulfoxide solution sublingually once a day for 5 consecutive days.The serum levels of inflammatory factors were detected by enzyme-linked immunosorbent assays.The histopathological changes in pancreatic tissues were detected by Hematoxylin-eosin staining.The relative protein expressions of tumor necrosis factor receptor-1(TNF-R1),TNF-R1-associated death domain protein(TRADD),and receptor interacting protein kinase 1(RIP1)in pancreatic tissues were detected by Western blotting.Results Compared with the control group,the serum levels of interleukin-6(IL-6),tumor necrosis factorα(TNFα),malondialdehyde(MDA),and calcitonin gene-related peptide(CGRP),the histopathological scores,and the protein expressions of TNF-R1,TRADD and RIP1 were higher in the other groups(P<0.05).These indicators were lower in the experimental-L group and the experimental-H group than those in the model group(P<0.05),and they were even lower in the experimental-H group than those in the experimental-L group(P<0.05).Compared with the control group,the serum SOD activity was lower in the other groups(P<0.05).In contrast,the serum SOD activity was higher in the experimental-H group than in the experimental-L group(P<0.05).Conclusions Colchicine can ameliorate the inflammation and oxidative stress and improve the microcirculation in AP rats.It is speculated that the underlying mechanism is dependent on the TNF-α/TNF-R1 signaling pathway.