异甘草素减轻重症急性胰腺炎小鼠心肌损伤机制

Mechanism of isoliquiritigenin underlying severe acute pancreatitis-induced myocardial injury in mice

目的探讨异甘草素(ISL)对重症急性胰腺炎(SAP)心肌损伤的保护机制。方法将雄性小鼠36只随机分为对照组、SAP组和ISL组,每组12只,SAP组和ISL组采用L-精氨酸制备小鼠SAP模型,ISL组首次注射精氨酸24h后腹腔注射ISL100mg/kg,对照组和SAP组给予等量DMSO。检测各组血清肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)及心脏组织超氧化物歧化酶(SOD),谷胱甘肽活性、丙二醛水平。采用Western blot法检测心脏组织中核转录因子-E2相关因子2(Nrf2)及血红素加氧酶(HO-1)蛋白表达水平。结果 SAP组小鼠心肌细胞肿胀,部分细胞崩解,心肌纤维结构消失,有较多炎性细胞浸润,ISL组心肌损害减轻。与对照组比较,SAP组SOD及谷胱甘肽活性明显降低,丙二醛及Nrf2、HO-1蛋白表达水平明显升高(P<0.05)。与SAP组比较,ISL组cTnI、CK-MB、LDH、丙二醛水平明显下降,SOD[(102.1±10.4)U/mg vs (81.2±7.7)U/mg]及谷胱甘肽活性[(16.2±2.8)U/mg vs (11.2±3.6)U/mg]明显升高,且更进一步激活了Nrf2、HO-1蛋白水平表达,差异有统计学意义(P<0.05)。结论 ISL可能通过激活心脏组织中Nrf2/HO-1通路,减轻SAP诱导的心肌损伤。

Objective To study the mechanism of isoliquiritigenin(ISL)underlying severe acute pancreatitis(ASP)-induced myocardial injury in mice.Methods Thirty-six male mice were randomly divided into control group(n=12),SAP group(n=12)and ISL group(n=12).A SAP model of mice was induced by L-arginine.The mice in ISL group underwent intraperitoneal L-arginine(100 mg/kg)injection followed by intraperitoneal ISL(100 mg/kg)injection after 24 h while those in control group and SAP group received the same volume of DMSO.The serum levels of cTnI,CK-MB,LDH,SOD,GSH and MDA were measured.The expressions of Nrf2 and HO-1 protein were detected by Western blot.Results Swollen myocytes,disintegrative myocytes,disappeared myocardial fibrous structure and inflammatory cell infiltration were detected in SAP group.The injury of myocytes was alleviated in ISL group.The expression levels of SOD and GSH were significantly lower while those of MDA,Nrf2 and HO-1 protein were significantly higher in SAP group than in control group(P<0.05).The serum levels of cTnI,CK-MB and MDA were significantly lower while those of GSH were significantly higher in ISL group than in SAP group(P<0.05).Conclusion ISL can alleviate SAP-induced myocardial injury by activating the Nrf2/HO-1 pathway in myocardial tissue.