盐酸小檗碱对小鼠重症急性胰腺炎的作用机制  

Mechanism of berberine hydrochloride on mice severe acute pancreatitis

作　　者：晏殊[1] 黄歆[1] 汪瑜[1] 钟振东[2] 龙丹[3] 

机构地区：[1]成都市第七人民医院普外科,610041 [2]四川省医学科学院.四川省人民医院病理科,四川成都610072 [3]四川大学华西医院移植工程与移植免疫重点实验室,四川成都610041

出　　处：《国际消化病杂志》2018年第1期58-63,共6页International Journal of Digestive Diseases

基　　金：四川省卫生厅项目(16PJ209)

摘　　要：目的研究盐酸小檗碱(BH)对小鼠重症急性胰腺炎的影响,并探讨其潜在的机制。方法使用雨蛙肽和脂多糖诱导小鼠重症急性胰腺炎。造模后按体质量随机分为模型组、氯高铁血红素组(50mg·kg^(-1)·d^(-1),灌胃)、BH组(50mg·kg^(-1)·d^(-1),灌胃),另设正常对照组,每组各10只。连续给药7d后,测定各组小鼠胰腺重量指数。ELISA法测定血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血红素加氧酶^(-1)(HO^(-1))、白细胞介素^(-1)0(IL^(-1)0)、淀粉酶和脂肪酶含量,同时测定胰腺HO^(-1)、CO、丙二醛(MDA)、超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)表达水平;对胰腺病理组织进行评分;RT-qPCR检测胰腺TNF-α、IL-6、IL^(-1)0和HO^(-1) mRNA表达水平;Western blot检测胰腺HO^(-1)、IκB-α、核因子κB(NF-κB)p65、Lamin B蛋白表达水平;免疫组织化学检测胰腺NF-κB p65表达水平。结果与模型组比较,BH组小鼠胰腺重量指数明显降低(P<0.05);血清IL-6、TNF-α、淀粉酶和脂肪酶含量显著降低(P<0.01),HO^(-1)和IL^(-1)0含量显著升高(P<0.01);胰腺HO^(-1)、CO和SOD含量显著升高(P<0.01),MDA和MPO含量显著降低(P<0.01);胰腺病理形态评分显著降低(P<0.01);胰腺TNF-α和IL-6mRNA表达显著降低(P<0.01),IL^(-1)0和HO^(-1)mRNA表达显著升高(P<0.01);HO^(-1)和IκB-α蛋白表达显著升高(P<0.01),NF-κB p65蛋白表达显著降低(P<0.01),NF-κB p65阳性细胞率显著降低(P<0.01)。结论 BH可通过激活HO^(-1)活性介导小鼠胰腺炎性损伤和氧化应激损伤,其机制可能与抑制NF-κB活性有关。Objective This paper attempts to study the effect of berberine hydrochloride on acute severe pancreatitis in mice and to explore its potential mechanism.Methods Mice acute pancreatitis was induced by rumen peptide and lipopolysaccharide.The animals were randomly divided into the model group,the Hemin(50 mg·kg^(^(-1))·d^(^(-1)),intragastrical administration)group,and the berberine hydrochloride group(50 mg·kg^(^(-1))·d^(^(-1)),intragastrical administration),10 in each group.After 7 days of continuous administration,the pancreas weight index of each group was determined.The levels of serum IL-6,TNF-α,HO^(^(-1)),IL^(^(-1))0,amylase and lipase were measured by using the ELISA method.The contents of HO^(^(-1)),CO,MDA,SOD and MPO in pancreas were measured.RT-qPCR was used to detect the levels of TNF-α,IL-6,IL^(^(-1))0 and HO^(^(-1)) mRNA in pancreas.The expressions of HO^(^(-1)),IκB-α,NF-κB p65 and Lamin B were detected by Western blot.Immunohistochemistry was used to detect the pancreatic NF-κB p65 expression level.Results Compared with the model group,the pancreas weight index of BH group was significantly decreased(P<0.05),and the levels of serum IL-6,TNF-α,amylase and lipase were significantly decreased(P<0.01).The contents of MDA and MPO in the pancreas were significantly increased(P<0.01),and the contents of HO^(-1),CO and SOD were significantly increased(P<0.01).The expression of TNF-αand IL-6 mRNA in the pancreas was significantly decreased(P<0.01),the expression of IL^(-1)0 and HO^(-1) mRNA was significantly increased(P<0.01),the expression of NF-κB p65 protein was significantly decreased(P<0.01),and the rate of NF-κB p65 positive cells was significantly decreased(P<0.01).Conclusions Berberine hydrochloride can induce inflammatory injury and oxidative stress injury in mice by activating HO^(-1) activity.The mechanism may be related to the inhibition of NF-κB activity.

关 键 词：盐酸小檗碱 急性胰腺炎 血红素加氧酶1 核因子-ΚB 

分 类 号：R576[医药卫生—消化系统]