左旋紫草素基于调节NF-κB途径和NLRP3炎性体轴减轻急性胰腺炎动物模型胰腺组织损伤作用  

Effect of L-shikonin on Pancreatic Tissue Injury in Animal Models of Acute Pancreatitis Based on Regulating the NF-κB Pathway and the NLRP3 Inflammasome Axis

作　　者：余洁 杜恒 秦清 吴安定[1] 万里鹏[1] YU Jie;DU Heng;QIN Qing;WU Anding;WAN Lipeng(Huanggang Central Hospital,Huanggang 438000,Hubei,China)

机构地区：[1]黄冈市中心医院,湖北黄冈438000

出　　处：《辽宁中医药大学学报》2024年第9期22-27,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家卫生健康委医院管理研究所项目(NIHA23JXH055);湖北省卫生健康委员会科研项目(WJ2021M083)。

摘　　要：目的探究左旋紫草素对急性胰腺炎动物模型胰腺组织损伤的作用及其作用机制。方法选取SD大鼠48只,随机分为假手术组、模型组、左旋紫草素低剂量组和左旋紫草素高剂量组4组,每组12只。采用胆胰管逆行注射5%牛磺酸钠溶液构建急性胰腺炎模型,左旋紫草素低剂量组和高剂量组在造模前1 h及造模后分别腹腔注射左旋紫草素(10、20 mg/kg),模型组及假手术组给予等量0.9%氯化钠溶液。采用HE染色观察胰腺及心肌组织病理变化,免疫组织化学染色和蛋白免疫印迹(Western blot)分析NF-κB信号通路和NLRP3炎性体轴相关蛋白的表达情况,酶联免疫吸附法检测各组大鼠血清中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、肌酸激酶同工酶(CK-MB)水平。结果与假手术组相比,模型组大鼠的胰腺及心肌组织出现明显的病理损伤,NF-κB、NLRP3蛋白阳性率及相关蛋白NF-κB p65、p-p56、NLRP3、半胱氨酸蛋白酶1(Caspase-1)、ASC蛋白的相对表达水平显著升高(P<0.01),而IκBα的相对表达水平显著降低(P<0.01),且血清IL-1β、TNF-α、CK-MB水平显著升高(P<0.01)。与模型组相比,左旋紫草素低剂量组和高剂量组大鼠的胰腺及心肌组织损伤程度减轻,NF-κB、NLRP3蛋白阳性率及相关蛋白NF-κB p65、p-p56、NLRP3、Caspase-1、ASC蛋白的相对表达水平显著降低(P<0.01),IκBα的相对表达水平显著升高(P<0.01),血清IL-1β、TNF-α、CK-MB水平显著降低(P<0.01),且左旋紫草素高剂量组的效果优于低剂量组。结论左旋紫草素能够通过调节NF-κB信号通路和NLRP3炎性体轴减轻急性胰腺炎动物模型胰腺组织损伤,为左旋紫草素在急性胰腺炎的治疗提供重要的参考。Objective To investigate the effect and mechanism of L-shikonin on pancreatic tissue injury in an animal model of acute pancreatitis.Methods 48 SD rats were selected and randomly divided into four groups:sham-operation group,model group,low-dose of L-shikonin group,and high-dose of L-shikonin group,with 12 rats in each group.An acute pancreatitis model was established by retrograde injection of 5%sodium taurate solution into the biliary pancreatic duct.The low-dose and high-dose of L-shikonin groups were intraperitoneally injected with L-shikonin(10,20 mg/kg)1 hour before and after modeling.The model group and sham-operation group were given equal amounts of 0.9%sodium chloride solution.HE staining was used to observe the pathological changes in pancreatic and myocardial tissues.Immunohistochemistry staining and Western blot were used to analyze the expression of NF-κB signaling pathway and NLRP3 inflammatory axis related proteins.Enzyme linked immunosorbent assay was used to detect the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and creatine kinase isoenzyme(CK-MB)in the serum of each group of rats.Results Compared with the sham-operation group,the pancreatic and myocardial tissues of the model group showed obvious pathological damage,the positive rates of NF-κB and NLRP3 proteins and the relative expression levels of NF-κB p65,p-p56,NLRP3,Caspase-1 and ASC proteins were significantly increased(P<0.01),while the relative expression level of IκBαwas significantly decreased(P<0.01),and the serum levels of IL-1β,TNF-αand CK-MB were significantly increased(P<0.01).Compared with the model group,the degree of pancreatic and myocardial tissue injury was alleviated in the low-dose and high-dose of L-shikonin group.The positive rates of NF-κB and NLRP3 proteins and the relative expression levels of NF-κB p65,p-p56,NLRP3,Caspase-1 and ASC proteins were significantly decreased(P<0.01),and the relative expression level of IκBαwas significantly increased(P<0.01),and the serum levels of IL-1�

关 键 词：急性胰腺炎 左旋紫草素 核因子ΚB信号通路 NLRP3炎性体轴 

分 类 号：R256.3[医药卫生—中医内科学] R576[医药卫生—中医学]