妊娠期肝内胆汁淤积症孕妇血清氧化应激水平及与妊娠结局的关系

Relationship between serum oxidative stress level and pregnancy outcome in pregnant women with intrahepatic cholestasis of pregnancy

目的分析妊娠期肝内胆汁淤积症孕妇血清氧化应激水平与妊娠结局的关系。方法回顾性选取2020年2月至2022年2月海南医学院第一附属医院收治的妊娠期肝内胆汁淤积症孕妇80例,依据疾病严重程度分为重度组(血清总胆汁酸水平≥40μmol/L)、轻度组(血清总胆汁酸水平11~39μmol/L),每组各40例。另回顾性选取同期同院健康体检孕妇40例作为健康组。统计分析3组孕妇的血清氧化应激指标[丙二醛、一氧化氮、超氧化物歧化酶(SOD)]、炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-10、IL-12]、肝功能指标[丙氨酸转移酶(ALT)、天冬氨酸转移酶(AST)、总胆汁酸(TBA)]水平、胎盘发育受损及功能障碍发生情况、妊娠结局,分析血清氧化应激指标水平与妊娠结局的关系。结果重度组、轻度组孕妇的血清一氧化氮、SOD水平均低于健康组,血清丙二醛水平均明显高于健康组,且重度组孕妇的血清丙二醛水平明显高于轻度组,血清一氧化氮、SOD水平均明显低于轻度组,差异均有统计学意义(P<0.05)。重度组、轻度组孕妇的血清TNF-α、IL-6、IL-12水平均明显高于健康组,血清IL-10水平均明显低于健康组,且重度组孕妇的血清TNF-α、IL-6、IL-12水平均明显高于轻度组,血清IL-10水平明显高于轻度组,差异均有统计学意义(P<0.05)。重度组、轻度组孕妇的血清ALT、AST、TBA水平均明显高于健康组,且重度组孕妇的血清ALT、AST、TBA水平均明显高于轻度组,差异均有统计学意义(P<0.05)。重度组、轻度组孕妇的胎盘发育受损及功能障碍发生率分别为17.50%(7/40)、10.00%(4/40),均高于健康组[2.50%(1/40)],重度组孕妇的胎盘发育受损及功能障碍发生率高于轻度组,差异均有统计学意义(P<0.05)。重度组、轻度组孕妇的不良妊娠结局发生率分别为55.00%(22/40)、22.50%(9/40),均明显高于健康组5.00%(2/40),重度组孕妇的不良妊娠结局发生率明显高于轻度组,差异均有统计学意义(P<0.05)。重度组、轻度组、健康组孕妇的不良妊娠结局与血清一氧化氮、SOD水平均呈显著负相关(P<0.05),与血清丙二醛水平呈显著正相关(P<0.05)。结论妊娠期肝内胆汁淤积症孕妇存在显著氧化应激状态,炎症因子高表达,肝功能受损,血清氧化应激水平与妊娠结局的关系密切。

Objective To analyze the relationship between pregnancy outcome and serum oxidative stress level in pregnant women with intrahepatic cholestasis during pregnancy.Methods A total of 80 pregnant women with intrahepatic cholestasis during pregnancy who admitted to the First Affiliated Hospital of Hainan Medical University from February 2020 to February 2022 were retrospectively selected.According to the severity of the disease,they were divided into severe group(serum total bile acid level≥40μmol/L)and mild group(serum total bile acid level 11-39μmol/L),with 40 cases in each group.In addition,40 healthy pregnant women who underwent physical examination in same hospital during the same period were retrospectively selected as the healthy group.The levels of serum oxidative stress indicators[malondialdehyde,nitric oxide,superoxide dismutase(SOD)],inflammatory factors[tumor necrosis factor(TNF-α),interleukin(IL)-6,IL-10,IL-12],liver function indicators[alanine transferase(ALT),aspartic acid transferase(AST),total bile acid(TBA)],placental development impairment and dysfunction,and pregnancy outcome of pregnant women in the three groups were statistically analyzed,and the relationship between serum oxidative stress index level and pregnancy outcome of the three groups was analyzed.Results The levels of serum nitric oxide and SOD in severe group and mild group were lower than those in healthy group,the levels of serum malondialdehyde were higher than those in healthy group,and the levels of serum nitric oxide and SOD in severe group were lower than those in mild group,and the levels of serum malondialdehyde were higher than those in mild group,the differences were statistically significant(P<0.05).The levels of serum TNF-α,IL-6 and IL-12 in severe and mild group were higher than those in healthy group,the serum levels of IL-10 in severe and mild groups were lower than those in healthy group,and the serum levels of IL-10 in severe group were higher than those in mild group,the levels of serum TNF-α,IL-6 and IL-12 were higher than those in mild group,the differences were statistically significant(P<0.05).The levels of serum ALT,AST and TBA in severe group and mild group were higher than those in healthy group,and the levels of serum ALT,AST and TBA in severe group were higher than those in mild group,the differences were statistically significant(P<0.05).The incidences of impaired placental development and dysfunction in severe and mild groups were 17.50%(7/40)and 10.00%(4/40),which were higher than that in healthy group[2.50%(1/40)],the incidences of impaired placental development and dysfunction in severe group were higher than those in mild group,the differences were statistically significant(P<0.05).The incidences of adverse pregnancy outcomes in severe and mild groups were 55.00%(22/40)and 22.50%(9/40),which were higher than that in healthy group[5.00%(2/40)],the incidence of adverse pregnancy outcomes in severe group was higher than that in mild group,the differences were statistically significant(P<0.05).Adverse pregnancy outcomes in severe group,mild group and healthy group were significantly negatively correlated with serum nitric oxide and SOD levels(P<0.05),and significantly positively correlated with serum MDA levels(P<0.05).Conclusion There is a close relationship between pregnancy outcome and serum oxidative stress level in pregnant women with intrahepatic cholestasis of pregnancy.The higher the level of serum oxidative stress,the worse the pregnancy outcome.