熊去氧胆酸与地塞米松联合应用对重度妊娠期肝内胆汁淤积症患者的临床治疗效果、血清SIRT1/NF-κB p65信号通路及炎症因子的影响
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摘要
目的观察熊去氧胆酸与地塞米松联合应用治疗重度妊娠期肝内胆汁淤积症(ICP)患者的临床效果及对炎症因子的影响。方法选取2016年1月-2018年3月鄂州市中心医院收治的ICP患者77例随机分为对照组40例和研究组37例,对照组应用熊去氧胆酸治疗,研究组应用熊去氧胆酸联合地塞米松治疗。比较两组患者治疗前、后瘙痒评分、妊娠结局变化及血清肝功能指标血清总胆汁酸(TBA)、总胆红素(TBIL)、谷丙转氨酶(ALT)、谷草转氨酶(AST)变化; Real-time PCR检测入组患者血清SIRT1及NF-κB p65表达; ELISA法检测治疗前、后血清肿瘤坏死因子-α(TNF-α)、白细胞介素-4 (IL-4)、IL-12及IL-18含量。结果①与对照组相比,研究组治疗有效率升高、不良妊娠结局发生率降低,差异有统计学意义(P <0. 05);②与治疗前相比,治疗后两组患者瘙痒评分、血清肝功能指标ALT、AST、TBA、TBIL、TNF-α、IL-12、IL-18含量及NF-κB p65 m RNA表达均降低,IL-4含量和SIRT1 m RNA表达升高,差异均有统计学意义(P<0. 05);③与对照组治疗后相比,研究组患者瘙痒评分、血清ALT、AST、TBA、TBIL、TNF-α、IL-12、IL-18含量及NF-κB p65mRNA表达更低,IL-4含量和SIRT1 m RNA表达升高,差异有统计学意义(P<0. 05)。结论熊去氧胆酸联合地塞米松治疗重度ICP效果较好,其机制可能通过影响SIRT1/NF-κB p65信号通路,进而减轻肝脏炎症反应因子,改善临床症状及妊娠结局,值得推广。
Objective To observe the clinical efficacy of ursodeoxycholic acid combined with dexamethasone in treatment of severe intrahepatic cholestasis of pregnancy( ICP) and the influence on serum SIRT1/NF-κB p65 signaling pathway and inflammatory factors. Methods From January 2016 to March 2018,77 patients with ICP treated in Ezhou Central Hospital were randomly divided into control group and study group. The patients in control group were treated by ursodeoxycholic acid,and the patients in study group were treated by ursodeoxycholic acid combined with dexamethasone. The scores of pruritus before and after treatment,the changes of pregnancy outcomes and serum levels of total bile acid( TBA),total bilirubin( TBIL),glutamate-pyruvic transaminas e( ALT),and glutamic oxalacetic transaminase( AST) in the two groups were compared. Real-time PCR was used to detect the expression levels of serum SIRT1 and NF-κB p65.ELISA was used to detect the levels of serum tumor necrosis factor-α( TNF-α),interleukin-4( IL-4),interleukin-12( IL-12),and interleukin-18( IL-18) before and after treatment. Results Compared with control group,the effective rate increased in study group,the incidence rate of adverse pregnancy outcome decreased( P<0. 05). Compared with before treatment,pruritus scores,the levels of ALT,AST,TBA,TBIL,TNF-α,IL-12,IL-18,and NF-κB p65 m RNA in the two groups decreased,the levles of IL-4 and SIRT1 mRNA increased( P<0. 05). After treatment,compared with control group,pruritus score,the levels of ALT,AST,TBA,TBIL,TNF-α,IL-12,IL-18,and NF-κB p65 mRNA in study group decreased,the levles of IL-4 and SIRT1 mRNA increased( P<0. 05). Conclusion The effect of ursodeoxycholic acid combined with dexamethasone in treatment of severe ICP is good,the therapy can alleviate hepatic inflammatory response factors and improve clinical symptoms and pregnancy outcome by affecting SIRT1/NF-κB p65 signaling pathway,which is worthy of promotion.
Objective To observe the clinical efficacy of ursodeoxycholic acid combined with dexamethasone in treatment of severe intrahepatic cholestasis of pregnancy( ICP) and the influence on serum SIRT1/NF-κB p65 signaling pathway and inflammatory factors. Methods From January 2016 to March 2018,77 patients with ICP treated in Ezhou Central Hospital were randomly divided into control group and study group. The patients in control group were treated by ursodeoxycholic acid,and the patients in study group were treated by ursodeoxycholic acid combined with dexamethasone. The scores of pruritus before and after treatment,the changes of pregnancy outcomes and serum levels of total bile acid( TBA),total bilirubin( TBIL),glutamate-pyruvic transaminas e( ALT),and glutamic oxalacetic transaminase( AST) in the two groups were compared. Real-time PCR was used to detect the expression levels of serum SIRT1 and NF-κB p65.ELISA was used to detect the levels of serum tumor necrosis factor-α( TNF-α),interleukin-4( IL-4),interleukin-12( IL-12),and interleukin-18( IL-18) before and after treatment. Results Compared with control group,the effective rate increased in study group,the incidence rate of adverse pregnancy outcome decreased( P<0. 05). Compared with before treatment,pruritus scores,the levels of ALT,AST,TBA,TBIL,TNF-α,IL-12,IL-18,and NF-κB p65 m RNA in the two groups decreased,the levles of IL-4 and SIRT1 mRNA increased( P<0. 05). After treatment,compared with control group,pruritus score,the levels of ALT,AST,TBA,TBIL,TNF-α,IL-12,IL-18,and NF-κB p65 mRNA in study group decreased,the levles of IL-4 and SIRT1 mRNA increased( P<0. 05). Conclusion The effect of ursodeoxycholic acid combined with dexamethasone in treatment of severe ICP is good,the therapy can alleviate hepatic inflammatory response factors and improve clinical symptoms and pregnancy outcome by affecting SIRT1/NF-κB p65 signaling pathway,which is worthy of promotion.
引文
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[7]谭白菊,李玉梅,冯小平,等.丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症患者免疫功能及疗效的影响[J].国际妇产科学杂志,2016,43(5):563-566.
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[9]李广清,林晓斌,胡超钰,等.丁二磺酸腺苷蛋氨酸联合熊去氧胆酸对妊娠期肝内胆汁淤积症患者肝功能及妊娠结局的影响[J].现代生物医学进展,2018,18(11):2181-2184.
[10]申铁英,郭秀云,罗万翠.地塞米松联合腺苷蛋氨酸治疗妊娠期肝内胆汁淤积症的疗效及对患者肝功能、炎性细胞因子水平的影响[J].中国妇幼保健,2017,32(18):4333-4336.
[11]张丽明,李素玉,段栋时,等.胆瘀方结合熊去氧胆酸片及丁二磺酸腺苷蛋氨酸治疗妊娠期肝内胆汁淤积症的临床分析[J].空军医学杂志,2018,34(1):65-68.
[12]Hirschfield GM,Mason A,Luketic V,et al.Efficacy of obetic holic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid[J].Gastroenterology,2015,148(4):751-761.
[13]葛星,徐叶清,黄三唤,等.妊娠期肝内胆汁淤积症对分娩结局影响的出生队列研究[J].中华流行病学杂志,2016,37(2):187-191.
[14]Ataalla WM,Ziada DH,Gaber R,et al.The impact of total bile acid levels on fetal cardiac function in intrahepatic cholestasis of pregnancy using fetal echocardiography:a tissue Doppler imaging study[J].Matern Fetal Neonatal Med,2016,29(9):1445-1450.
[15]张莉,李晓丽,兰远霞.妊娠期肝内胆汁淤积症孕妇血液流变学、凝血功能和细胞因子的变化及临床意义[J].海南医学院学报,2015,21(8):1088-1090.
[16]李丽,汪光慧,孙建群.地塞米松治疗妊娠期肝内胆汁淤积症的临床研究[J].中国妇幼保健,2013,28(8):1355-1357.
[17]李桂香,刘玲玲,李丽,等.丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症患者肝功能及血清TNF-α,IL-12水平的影响[J].现代生物医学进展,2017,17(19):3765-3768.
[18]Huang W,Shang W,Wang H,et al.Sirtl overexpression protects murine osteoblasts against TNF-α-induced injury in vitro by suppressing the NF-κB signaling pathway[J].Acta Pharmacol Sin,2012,33(5):668-674.
[19]蔡艾杞,刘路遥,高燕洪,等.妊娠期肝内胆汁淤积症的研究进展[J].现代妇产科进展,2016,11(25):871-873.
[20]向华,张笃华,易宇凌,等.妊娠期肝内胆汁淤积症外周血IL-12及TNF-α检测的临床意义[J].中国妇幼保健,2013,28(8):1335-1337.
[21]Keitel V,Dr9ge C,Stepanow S,et al.Intrahepatic cholestasis of pregnancy(ICP):case report and review of the literature[J].ZGastroenterol,2016,54(12):1327-1333.
[22]李珺.丁二磺酸腺苷蛋氨酸与地塞米松联合对妊娠期肝内胆汁淤积症患者疗效观察及对患者炎症因子及肝功能影响[J].中国中西医结合消化杂志,2018,26(1):58-61.
[2]Mella MT,Kohari K,Lambertini L,et al.Mitochondrial gene expression profiles are associated with intrahepatic cholestasis of pregnancy[J].Placenta,2016,45(1):16-23.
[3]Ovadia C,Williamson C.Intrahepatic cholestasis of pregnancy:recent advances[J].Clin Dermatol,2016,34(3):327-334.
[4]梁辉标,吕杰强.妊娠期肝内胆汁瘀积症肝功能、炎症细胞因子变化临床分析[J].中国妇幼保健,2016,31(1):55-57.
[5]Brouwers L,Koster MP,Oudijk MA,et al.Intrahepatic cholestasis of pregnancy:maternal and fetal outcomes associated with elevated bile acid levels[J].Am J Obstet Gynecol,2015,212(1):100.e1-100.e7.
[6]樊阳阳,张京京,王影,等.S-腺苷蛋氨酸联合熊去氧胆酸治疗妊娠期肝内胆汁淤积症的临床疗效及对肝功能、炎症因子的影响[J].药物评价研究,2018,41(2):267-271.
[7]谭白菊,李玉梅,冯小平,等.丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症患者免疫功能及疗效的影响[J].国际妇产科学杂志,2016,43(5):563-566.
[8]贺晶,杨慧霞,漆洪波,等.妊娠期肝内胆汁淤积症诊疗指南(2015)[J].临床肝胆病杂志,2015,31(10):1575-1578.
[9]李广清,林晓斌,胡超钰,等.丁二磺酸腺苷蛋氨酸联合熊去氧胆酸对妊娠期肝内胆汁淤积症患者肝功能及妊娠结局的影响[J].现代生物医学进展,2018,18(11):2181-2184.
[10]申铁英,郭秀云,罗万翠.地塞米松联合腺苷蛋氨酸治疗妊娠期肝内胆汁淤积症的疗效及对患者肝功能、炎性细胞因子水平的影响[J].中国妇幼保健,2017,32(18):4333-4336.
[11]张丽明,李素玉,段栋时,等.胆瘀方结合熊去氧胆酸片及丁二磺酸腺苷蛋氨酸治疗妊娠期肝内胆汁淤积症的临床分析[J].空军医学杂志,2018,34(1):65-68.
[12]Hirschfield GM,Mason A,Luketic V,et al.Efficacy of obetic holic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid[J].Gastroenterology,2015,148(4):751-761.
[13]葛星,徐叶清,黄三唤,等.妊娠期肝内胆汁淤积症对分娩结局影响的出生队列研究[J].中华流行病学杂志,2016,37(2):187-191.
[14]Ataalla WM,Ziada DH,Gaber R,et al.The impact of total bile acid levels on fetal cardiac function in intrahepatic cholestasis of pregnancy using fetal echocardiography:a tissue Doppler imaging study[J].Matern Fetal Neonatal Med,2016,29(9):1445-1450.
[15]张莉,李晓丽,兰远霞.妊娠期肝内胆汁淤积症孕妇血液流变学、凝血功能和细胞因子的变化及临床意义[J].海南医学院学报,2015,21(8):1088-1090.
[16]李丽,汪光慧,孙建群.地塞米松治疗妊娠期肝内胆汁淤积症的临床研究[J].中国妇幼保健,2013,28(8):1355-1357.
[17]李桂香,刘玲玲,李丽,等.丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症患者肝功能及血清TNF-α,IL-12水平的影响[J].现代生物医学进展,2017,17(19):3765-3768.
[18]Huang W,Shang W,Wang H,et al.Sirtl overexpression protects murine osteoblasts against TNF-α-induced injury in vitro by suppressing the NF-κB signaling pathway[J].Acta Pharmacol Sin,2012,33(5):668-674.
[19]蔡艾杞,刘路遥,高燕洪,等.妊娠期肝内胆汁淤积症的研究进展[J].现代妇产科进展,2016,11(25):871-873.
[20]向华,张笃华,易宇凌,等.妊娠期肝内胆汁淤积症外周血IL-12及TNF-α检测的临床意义[J].中国妇幼保健,2013,28(8):1335-1337.
[21]Keitel V,Dr9ge C,Stepanow S,et al.Intrahepatic cholestasis of pregnancy(ICP):case report and review of the literature[J].ZGastroenterol,2016,54(12):1327-1333.
[22]李珺.丁二磺酸腺苷蛋氨酸与地塞米松联合对妊娠期肝内胆汁淤积症患者疗效观察及对患者炎症因子及肝功能影响[J].中国中西医结合消化杂志,2018,26(1):58-61.