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目的 探讨巨噬细胞移动抑制因子(MIF)抑制剂ISO-1腹腔注射给药对妊娠晚期大鼠急性坏死性胰腺炎(ANP)大鼠胰腺和胎盘的保护作用及其量效关系.方法 SPF级妊娠晚期SD大鼠30只,随机(随机数字法)分为5组(n=6):假手术组(SO组)、ANP组、ISO-1预处理低剂量组(1.75 mg/kg,T1组)、中剂量组(3.5 mg/kg,T2组)和高剂量组(7.0 mg/kg,T3组).胆胰管逆行注射5％牛磺胆酸钠制备ANP模型.预处理组于造模前30 min经腹腔按低、中、高剂量注射溶解IOS-1的10％DMSO(2 mL/kg)溶液,SO组、ANP组于造模前30 min经腹腔注射10％ DMSO(2 ml/kg),术后6 h处死大鼠.测定大鼠血清中AMY、LIP、ALT及AST水平,光镜下观察大鼠胰腺、胎盘的组织病理变化.多个样本均数比较采用单因素方差分析,两组间比较采用t检验.结果 ANP组AMY、LIP、ALT和AST的水平(U/L)分别为(7 101.4±1 032.3)、(2 939.0±638.8)、(240.3±50.3)和(472.6 ±27.5),高于SO组的(2 268.7±293.8)、(681.1±109.9)、(56.4±15.3)和(110.9±15.5),差异具有统计学意义(P＜0.05);T1组AMY、LIP、ALT、AST的水平(U/L)为(4 349.5±439.5)、(1 968.9±515.2)、(155.0±41.8)和(373.7 ±64.9),低于ANP组,差异具有统计学意义(P＜0.05);T2组AMY、LIP、ALT、AST的水平(U/L)为(3 459.7±459.2)、(1 268.6±367.8)、(110.5±20.6)和(281.8±66.8),低于T1组,差异具有统计学意义(P＜0.05);T3组AMY、LIP、ALT、AST的水平(U/L)为(3 288.4±583.7)、(1198.1 ±328.5)、(100.6±13.2)和(272.9±66.5),同T2组比较差异无统计学意义(P＞0.05).ANP组胰腺、胎盘的病理评分分别为(12.3±1.5)分和(6.3±0.8)分,高于SO组(4.7±1.2)分和(0.5±0.5)分,差异具有统计学意义(P＜0.05);T1组胰腺、胎盘病理评分为(10.5±1.6)分和(5.1±0.7)分,低于ANP组,差异具有统计学意义(P＜0.05);TT2组胰腺、胎盘病理评分为(8.3±1.0)分和(3.0±0.6)分,低于T1组,差异具有统计学意义(P＜0.05);T3组胰腺、胎盘病理评分为(8.0±1.4)分和(2.8±0.8)分,同T2组比较差异无统计学意义(P＞0.05).结论 腹腔给予MIF抑制剂ISO-1对妊娠晚期大鼠A NP大鼠胰腺及胎盘具有保护作用,T2组(3.5 mg/kg)为改善妊娠晚期ANP大鼠胰腺及胎盘损伤安全、有效的最佳剂量.“,”Objective To explore the protective effects and dose-effect relationship of ISO-1,a MIF inhibitor,on pancreatic and placental injuries in rats with acute necrotizing pancreatitis (ANP) in late pregnancy.Methods Thirty SD rats at late pregnancy were randomly (random number) divided into five groups (n =6 in each group):sham operation group (SO group),acute necrotizing pancreatitis group (ANP group) and ISO-1 pretreatment group in different dosages:T1 group (1.75 mg/kg),T2 group (3.5 mg/kg) and T3 group (7.0 mg/kg).ANP rat model was induced by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct.In ISO-1 pretreatment group,ISO-1 dissolved in 10％ DMSO in different concentration was intra-peritoneal administered.The rats of SO group and ANP group were intra-peritoneal administered with 10％DMSO (2 mL/kg) 30 min before the ANP modeling.Rats were sacrificed 6 hours after modeling.The serum levels of amylase (AMY),lipase (LIP),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by biochemical analyzer.Pancreatic and placental pathological changes were evaluated under the optics microscope.All data were analyzed by using the One-way analysis of variance (ANOVA) or student t test.Results The serum levels (U/L) of AMY,LIP,ALT and AST in ANP group were (7 101.4 ± 1 032.3),(2 939.0 ±638.8),(240.3 ±50.3) and (472.6 ±27.5),which were significantly higher than (2 268.7±293.8),(681.1 ±109.9),(56.4±15.3) and (110.9±15.5) of SO group (P＜ 0.05).The levels (U/L) of AMY,LIP,ALTand ASTofT1 group were (4349.5±439.5),(1 968.9±515.2),(155.0 ± 41.8) and (373.7 ± 64.9),which were lower than those of ANP group (P ＜ 0.05).The level (U/L) of AMY,LIP,ALT and AST of T2 group were (3 459.7 ± 459.2),(1 268.6 ± 367.8),(110.5 ±20.6) and (281.8 ±66.8),which were lower than those ofT1 group (P＜0.05).The level (U/L) of AMY,LIP,ALT and AST of T3 group were (3288.4±583.7),(1 198.1±328.5),(100.6±13.2) and (272.9 ± 66.5),which were no significant difference from those of T2 group (P ＞ 0.05).The pancreatic and placental pathological scores of the ANP group were (12.3 ± 1.5) and (6.3 ±0.8),respectively,which were higher than (4.7 ± 1.2) and (0.5 ± 0.5) of SO group (P ＜ 0.05).The pancreatic and placental pathological scores of the T1 group were (10.5 ± 1.6) and (5.1 ± 0.7),respcetively,which were lower than those of ANP group (P ＜ 0.05).The pancreatic and placental pathological scores of T2 group were (8.3 ±1.0) and (3.0 ±0.6),which were lower than those of T1 group (P ＜ 0.05).The pancreatic and placenta pathological scores of T3 group were (8.0 ± 1.4) and (2.8 ± 0.8),respctively,which were no significant difference from those of T2 group (P ＞ 0.05).Conclusion The peritoneal administration of MIF inhibitor probably has protective effect on the pancreatic and placental injury in late pregnancy rat with ANP.ISO-1 dosage in T2 group (3.5 mg/kg) is the optimal and safe dosage for attenuating pancreatic and placental injuries in rat model of ANP in late pregnancy.