摘要
目的探讨小鼠重症急性胰腺炎(SAP)相关性心肌损害的发生机制和柚皮素的保护作用。方法将小鼠随机分为:对照组(control组)、模型组(SAP组)和柚皮素干预组(Nar组),每组12只。应用L-精氨酸(8%,4 mg/kg,p H=7. 0,间隔1h腹腔注射2次)制备小鼠SAP模型,Nar(200 mg/kg)溶于0. 5%CMC-Na中制备混悬液,在首次注射L-精氨酸后0、24和48 h腹腔注射。试剂盒检测血浆c Tn I、CK-MB及LDH浓度。实时荧光定量PCR和Western blot检测心脏组织NLRP3、caspase-1、ASC、IL-1βmRNA及蛋白表达。结果与对照组比较,SAP组小鼠胰腺组织水肿、腺泡细胞坏死、大量炎性反应细胞浸润。心肌细胞肿胀、部分细胞崩解、心肌纤维结构消失,并有较多炎性反应细胞浸润。血浆CK-MB、LDH及c Tn I水平明显升高(P<0. 05),心肌NLRP3、caspase-1、ASC及IL-1βmRNA和蛋白表达显著增高(P<0. 05)。柚皮素干预可以降低SAP小鼠血浆淀粉酶和脂肪酶水平、减轻胰腺组织损伤和心肌组织损伤,降低血浆CK-MB、LDH及CTn I水平(P<0. 01),下调心肌组织NLRP3、caspase-1、ASC及IL-1βmRNA (P<0. 01)和蛋白表达(P<0. 05)。结论柚皮素可能通过抑制心脏中NLRP3炎性小体激活保护SAP相关的心肌损伤。
Objective To investigate the molecular mechanism in SAP-induced myocardial injury in mice and to explore the protective role of naringenin.Methods Animals were randomly divided into 3 groups:control group,SAP group,and Nar group (n=12 each group).Mice were subjected to intraperitoneal injection with LPS (8%,4 mg/kg,pH=7) twice at 1 h intervals,to induce SAP model.Naringenin (200 mg/kg) were injected intraperitoneally 0,12 and 48 h after LPS injection.An automatic biochemical analyzer was used to measure the concentration of creatine kinase isoenzyme (CK-MB),lactate dehydrogenase (LDH) and cardiac troponin I(cTnI).Real time PCR and Western blot were used to analyze mRNA and protein levels of NLRP3,caspase-1,ASC and IL-1β.Results Compared to the control group,SAP gene showed not only edema,inflammatory cell infiltration and acinar cell necrosis inpancreatitis,but also the histological examination of swelled/disordered myocardial fibers and congested blood vessels in myocardium.Moreover,SAP-induced elevation of CK-MB/LDH and cTnI concentrations in serum and up-regulation NLRP3,caspase-1,ASC and IL-1β in both mRNA and protein levels in the heart tissues (P<0.05).Naringenin treatment inhibited SAP-induced elevation of CK-MB,LDH and cTnI concentrations in serum,alleviated SAP-induced pathological features.Moreover,compared to SAP group,naringenin treated group down-regulated NLRP3,ASC,caspase-1 and IL-1β expression in both mRNA(P<0.01) and protein levels in the heart(P<0.05).Conclusions Naringenin prevents severe acute pancreatitis-induced myocardial injury in mice by inhibiting NLRP3 inflammasome pathway.
作者
郑梅
胡文兰
阴英
孙华毅
王继红
赵兴山
ZHENG Mei;HU Wen-lan;YIN Ying;SUN Hua-yi;WANG Ji-hong;ZHAO Xing-shan(Department of Cardiovascular Medicine,Beijing Jishuitan Hospital,Beijing 100035,China;Department of Gastroenterology,Beijing Jishuitan Hospital,Beijing 100035,China)
出处
《基础医学与临床》
CSCD
2019年第2期213-217,共5页
Basic and Clinical Medicine
