目的 探讨白细胞介素(IL)18、IL-12及肿瘤坏死因子α(TNF-α)在妊娠期肝内胆汁淤积症(ICP)患者肝功能异常中的作用.方法 选择2010年4-9月在重庆医科大学附属第一医院就诊的62例ICP患者为ICP组,其中重度患者32例,轻度患者30例;同期就诊的30例健康孕妇为对照组,另选同期在重庆医科大学附属第一医院感染科住院的30例乙型肝炎妇女为肝炎组.采用ELISA 法测定IL-18、IL-12及TNF-α水平.检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平.同时观察ICP组及对照组的围产儿结局.结果 (1)肝炎组血清中IL-18、IL-12、TNF-α水平分别为(256±51)、(122±96)、(207±3)ng/L,ALT、AST水平分别为(363±174)、(359±237)U/L;ICP组IL-18、IL-12、TNF-α水平分别为(72±32)、(42±28)、(48±14)ng/L,ALT、AST水平分别为(201±128)、(132±87)U/L;对照组IL-18、IL-12、TNF-α水平分别为(43±13)、(10±3)、(33±9)ng/L,ALT、AST水平分别为(13±4)、(15±3)U/L.肝炎组血清中IL-18、IL-12、TNF-α及ALT、AST 水平显著高于ICP组和对照组,差异均有统计学意义(P＜0.05);ICP组也显著高于对照组,差异均有统计学意义(P＜0.05).(2)ICP组重度患者血清中IL-18、IL-12、TNF-α水平分别为(81±32)、(50±25)、(50±14)ng/L,ALT、AST水平分别为(269±111)、(181±73)U/L;轻度患者IL-18、IL-12、TNF-α水平分别为(48±18)、(17±4)、(40±10)ng/L,ALT、AST水平分别为(87±46)、(50±21)U/L,ICP组重度患者血清中IL-18、IL-12、TNF-α及AST、ALT水平显著高于轻度患者和对照组,差异均有统计学意义(P＜0.05);轻度患者血清中AST和ALT水平显著高于对照组,差异有统计学意义(P＜0.05).(3)ICP组重度患者的早产儿发生率(50%,16/32)及羊水胎粪污染率(31%,10/32)显著高于轻度患者[分别为7%(2/30)及3%(1/30)]和对照组[分别为3%(1/30)及3%(1/30)],差异均有统计学意义(P＜0.05);重度患者新生儿1分钟Apgar评分≤7分的例数(2例)与轻度患者(1例)和对照组(1例)比较,差异无统计学意义(P＞0.05).结论 IL-18、IL-12和TNF-α可能参与ICP患者肝细胞损害的过程,其水平升高有助于临床诊断ICP患者的肝细胞损害.%Objective To investigate the effect of Interleukin(IL)-18,IL-12 and tumor necrosis factor-α(TNF-α)in hepatic injury in intrahepatic cholestasis of pregnancy(ICP).Methods Sixty-two cases of ICP patients(ICP group),30 cases of normal pregnant women(control group)and 30 cases of hepatitis B(HBV) women (hepatitis group) were recruited. Serum IL-18, IL-12 and TNF-α were examined by ELISA. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined by automatic biochemical analysis instrument. Results ( 1 ) In hepatitis group, serum concentrations of IL-18,IL-12 and TNF-α were (256±51 ) ng/L, ( 122±96) ng/L and (207±3) ng/L; serum levels of ALT and AST were(363±174) U/L and (359 ±237) U/L, respectively. In ICP group, serum concentrations of IL18, IL-12 and TNF-α were (72±32) ng/L, (42 ±28) ng/L and (48±14) ng/L; serum levels of ALT and AST were (201 ±128) U/L and ( 132±87) U/L, respectively. While in control group, serum concentrations of IL-18, IL-12 and TNF-α were (43 ± 13) ng/L, ( 10±3) ng/L and (33±9) ng/L; serum levels of ALT and AST were (13 ~ 4) U/L and (15 ± 3) U/L, respectively. Serum IL-18, IL-12, TNF-α, ALT and AST levels in hepatitis group were significantly higher than those in ICP group and control group ( P ＜0. 05 ).Serum IL-18, IL-12, TNF-α, ALT and AST levels in ICP group were significantly higher than those in control group(P ＜ 0. 05 ). (2) In severe ICP subgroup, serum concentrations of IL-18, IL-12 and TNF-α were (81 ±32) ng/L, (50 ±25) ng/L and(50 ± 14) ng/L; serum levels of ALT and AST were (269 ± 111 ) U/L and (181±73) U/L In mild ICP subgroup, serum concentrations of IL-18, IL-12 and TNF-α were (48 ±18 ) ng/L, (17 ± 4 ) ng/L and (40 ± 10 ) ng/L; serum levels of ALT and AST were (87±46) U/L and (50 ±21 ) U/L, respectively. Serum IL-18, IL-12, TNF-α, ALT and AST levels in severe ICP subgroup were significantly higher than those in mild ICP subgroup and control group (P ＜ 0. 05). And serum ALT and AST levels in mild ICP subgroup were significantly higher than those in control group(P ＜0. 05). (3) There were 16 cases with preterm birth (50%, 16/32 ) and 10 cases with meconium-stained amniotic fluid( 31%, 10/32 ) in severe ICP subgroup, significantly higher than those in mild ICP subgroup ( P＜ 0. 05 ), which contained 2 preterm births ( 7%, 2/30) and 1 meconium-stained amniotic fluid (3%, 1/30). While in control group, the numbers were 1(3%, 1/30)and 1(3%, 1/30),respectively. As for the cases of neonates whose 1 minute Apgar score were not more than 7, there were 2 cases, 1 case and 1 case in severe ICP subgroup, mild ICP subgroup and control group, respectively,which showed no significant difference(P＞ 0. 05). Conclusion Serum IL-18, IL-12 and TNF-α may be involved in the process of hepatic injury of ICP.
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