血必净注射液调节线粒体N-甲酰肽/NLRP3炎症通路对重症急性胰腺炎大鼠模型的治疗机制  

Xuebijing Injection Regulates Mitochondrial N-formyl Peptides/NLRP3 Inflammatory Pathway to Treat Severe Acute Pancreatitis in Rats

作　　者：肖懿 冯志乔 张桂贤[3] 沈洪昇 李文畅[3] 李霞 高瑞芳 刘洪斌[3] XIAO Yi;FENG Zhi-qiao;ZHANG Gui-xian;SHEN Hong-sheng;LI Wen-chang;LI Xia;GAO Rui-fang;LIU Hong-bin(Graduate School,Tianjin Medical University,Tianjin 300070,China;Tianjin Chase Sun Pharmaceutical Co.Ltd.,Tianjin 301700,China;Tianjin Institute of Medical and Pharmaceutical Science,Tianjin 300020,China)

机构地区：[1]天津医科大学研究生院,天津300070 [2]天津红日药业股份有限公司,天津301700 [3]天津市医药科学研究所,天津300020

出　　处：《中国实验方剂学杂志》2022年第7期88-94,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：天津市卫生健康委员会科技人才培育项目基金项目(KJ20026)。

摘　　要：目的:探讨血必净注射液(XBJ)对牛磺胆酸钠(Na-Tc)诱导重症急性胰腺炎(SAP)大鼠模型的治疗作用。方法:将40只大鼠随机均分为5组,分别为假手术组、SAP模型组、XBJ低、中、高剂量组(4、8、12 mL·kg·d^(-1))。以胆胰管内逆行注射Na-Tc(1 mL·kg^(-1))制备SAP模型,XBJ在造模前3 d和造模后0.5 h进行腹腔注射给药。测量大鼠腹水量和胰腺组织湿质量比;采用苏木素-伊红(HE)染色观察胰腺组织病理变化;采用免疫组化检测胰腺组织甲酰肽受体1(FPR1)和核苷酸结合寡聚化结构域样受体3(NLRP3)的蛋白表达水平;采用蛋白免疫印迹法(Western blot)检测大鼠血浆中NADH-泛素氧化还原酶链1~6(MT-ND1、MT-ND2、MT-ND3、MT-ND4、MT-ND5、MT-ND6)的表达情况。结果:与假手术组比较,SAP模型组腹水量和胰腺湿质量比明显增加(P<0.05),胰腺组织病变严重,病理总评分明显上升(P<0.05),胰腺组织FPR1和NLRP3表达明显增多(P<0.05),血浆中MT-ND2表达明显降低(P<0.05),MT-ND1、MT-ND3和MT-ND6均明显增加(P<0.05),MT-ND4和MT-ND5无明显变化;与SAP模型组比较,XBJ各剂量治疗组大鼠腹水量和胰腺湿质量比显著减少(P<0.01),胰腺病变均有不同程度地改善,且胰腺组织FPR1和NLRP3表达均显著降低(P<0.01),血浆中MT-ND1、MT-ND3和MT-ND6表达均显著下降(P<0.01),MT-ND4表达下降,其中XBJ高剂量组尤甚(P<0.01),MT-ND5表达差异无统计学意义。结论:血必净注射液可有效治疗大鼠SAP,其机制可能与拮抗部分线粒体N-甲酰肽和FPR1/NLRP3介导的过度炎症反应相关。Objective:To investigate the therapeutic effect of Xuebijing injection(XBJ)on sodium taurocholate(Na-Tc)-induced severe acute pancreatitis(SAP)in rats.Method:Forty rats were randomly assigned into 5 groups:sham operation group,SAP model group,and low-,medium-,and high-dose(4,8,12 mL·kg·d^(-1),respectively)XBJ groups.SAP model was established by retrograde injection of Na-Tc(1 mL·kg^(-1))into the biliary and pancreatic ducts.XBJ was injected intraperitoneally 3 days before and 0.5 h after modeling.The ascitic fluid volume and the pancreas weight-to-body weight ratio were measured.The pathological changes of pancreatic tissue were observed via hematoxylin-eosin(HE)staining.The protein levels of formyl peptide receptor 1(FPR1)and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)in pancreatic tissue were detected by immunohistochemistry.Western blot was employed to determine the expression levels of NADH-ubiquinone oxidoreductase chains 1-6(MT-ND1,MT-ND2,MT-ND3,MT-ND4,MT-ND5,and MT-ND6)in rat plasma.Result:Compared with sham operation group,the SAP model group showcased increased ascitic fluid volume and pancreas weight-to-body weight ratio(P<0.05),serious lesions in pancreatic tissue,increased total pathological score(P<0.05),and up-regulated protein levels of FPR1 and NLRP3 in pancreatic tissue(P<0.05).The model group had lower MT-ND2 level(P<0.05)and higher MT-ND1,MT-ND3,and MT-ND6 levels in plasma(P<0.05)than the sham operation group,while MT-ND4 and MT-ND5 had no significant differences between the two groups.Compared with SAP model group,the XBJ treatment decreased ascitic fluid volume and pancreas weight-to-body weight ratio(P<0.01),ameliorated pancreatic lesions,and down-regulated the protein levels of FPR1 and NLRP3 in pancreatic tissue(P<0.01).The treatments,especially high-dose XBJ(P<0.01),down-regulated the expression of MT-ND1(P<0.01),MT-ND3(P<0.01),MT-ND6(P<0.01),and MT-ND4 and did not change that of MT-ND5.Conclusion:XBJ may antagonize partial mitochondrial N-formyl peptides and exces

关 键 词：重症急性胰腺炎 血必净注射液 线粒体N-甲酰肽 甲酰肽受体1 核苷酸结合寡聚化结构域样受体3 血府逐瘀汤 

分 类 号：R2-0[医药卫生—中医学] R33