摘要
目的:
探讨妊娠肝内胆汁淤积症(ICP)胎儿总胆汁酸浓度与胎儿胰腺内分泌功能变化之间的关系及对其胎儿生长发育的影响。
方法:
选择ICP患者30例作为研究组、正常妊娠孕妇30例作为对照组。采用放射免疫法测量两组胎儿脐动脉血清中胰岛素、胰高血糖素含量;循环酶法测定两组胎儿脐动脉血清总胆汁酸(TBA)水平;用氧化酶-过氧化物法测定两组胎儿脐动脉血清中葡萄糖浓度;新生儿均于生后15min内进行体重、身长的测量,计算新生儿庞代络指数(PI)。
结果:
1.研究组胰岛素(8.96±3.29mIU/L)及胰岛素/胰高血糖素比值(0.048±0.028)均低于对照组(10.10±3.68mIU/L,0.050±0.020),差异有统计学意义(P<0.05);脐动脉血胆汁酸(10.31±3.79umol/L)、胰高血糖素(235.32±56.59pg/ml)高于对照组(4.11±1.31umol/L,204.50±33.95pg/ml),差异有统计学意义(P<0.05);研究组脐动脉血血糖水平(3.44±1.14mmol/L)与对照组(3.57±1.17mmol/L)比较,差异无统计学意义(P>0.05)。
2.研究组新生儿体重及身长均明显低于对照组(3 162.92±478.28vs3497.97±393.00g,46.48±2.34vs49.31±1.88cm),差异均有统计学意义(P<0.01);研究组PI(3.13±0.23)明显高于对照组PI(2.92±0.29),其差别有统计学意义(P<0.01)。
3.研究组脐动脉血胆汁酸分别与胰岛素、胰高血糖素及胰岛素/胰高血糖素比值均呈直线关系,且随着胆汁酸的增加,胰岛素及胰岛素/胰高血糖素均降低,胰高血糖升高。(直线回归方程分别是Y_1=12.593-0.223X_1;Y_2=204.438+2.997X_2:Y_3=0.066-0.002X_3,P<0.01)。
4.研究组脐动脉胰岛素/胰高血糖素比值、胰岛素、血糖、胰高血糖素均是影响新生儿PI的因素,且影响程度依次减弱回归方程为Y=3.136+0.01X_1-0.056X_2+0.001X_3+7.167X_4,(P<0.01)。
结论:
1.ICP胎儿存在胰岛素分泌不足,胰高血糖素分泌增多,胰岛素/胰高血糖素比值下降,胎儿总胆汁酸可能是引起上述变化的原因之一。
2.ICP胎儿生长发育异常,与血糖、胰岛素、胰高血糖素及胰岛素/胰高血糖素比值有关,尤其与胰岛素/胰高血糖素比值关系最密切。
Objective
To investigate the relationship between fetal total bile acid and the change of fetal pancreatic endocrine function,and its influence to fetal growth and development in intrahepatic cholestasis of pregnancy (ICP).
Methods
The concentration of TBA、insulin、glucagons and glucose in the cord blood were measured in 30 fetuses of ICP (case group)and 30 fetuses of normogravidas(control group)after elective cesarean section. The cord blood TBA concentration was investigated by enzyme method and the cord concentration of insulin and glucagons were investigated by radioimmunoassay. The glucose was measured by oxidase-superoxide method. The neonatal weighs length and Ponderal index were measured within 15 minutes after parturition.
Results
1. The cord blood insulin concentration(8.96+3.29mIU/L) and insulin-to-glucagons ratio(0.048±0.028)in case group were significantly lower than that of the control(10.10±3.68mIU/L,0.050±0.020),The concentration of TBA(10.31±3.79umol/L)and glucagons(235.32±56.59pg/ml)in case group were obviously higher than those of the control(4.11±1.31umol/ L,204.50±33.95pg/ml),But no difference was shown in the concentration of glucose between case and control group[(3.44±1.14mmol/l) vs.(3.57±1.17mmol/L ),P>0.05].
2. The neonatal weight and length in case group were significantly lower than those of control [3162.92±478.28vs3497.97±393.00g, 46.48±2.34 vs49.31±1.88cm, P<0.01], while the Ponderal index in case group was significantly higher than that of control (3.13±0.23vs2.92±0.29,P<0.01).
3. The cord blood TBA concentration respectively showed straight line relationship with the cord blood insulin concentration、the cord blood glucagons concentration and insulin-to-glucagons ratio in case group. With the cord blood TBA concentration increasing, the cord insulin concentration and the ratio of insulin over glucagons decreased, meanwhile the cord blood glucagons concentration raised.(Linear regression equation were Y_1=12.593-0.223X_1;Y_2=204.438+2.997X_2;Y_3=0.066-0.002X_3,P<0.01).
4 . The cord blood glucose, insulin, glucagons and insulin-to-glucagons ratio were the factors that affect neonatal PI, and the order respectively was insulin-to-glucagons ratio, insulin, glucose, glucagons(P<0.01).General regression equation was Y=3.136+0.01X_1-0.056X_2+0.001X_3+7.167X_4 , (P<0.01).
Conclusion
1.Fetal pancreatic endocrine secretion exists hypoinsulinism, glucagons oversecretion, insulin-to-glucagons ratio decline in ICP and TBA may be one of the reasons that cause above-mentioned change.
2.ICP exists anomaly fetal growth and development, which is intimately correlated with cord blood glucose, insulin , glucagons and insulin-to-glucagons ratio, especially insulin-to-glucagons ratio.
引文
[1]邵勇,姚珍薇,罗红霞,等.孕鼠肝内胆汁淤积症致胎鼠心肌细胞凋亡[J].基础医学与临床,2007,27(1):85-86.
[2]刘静,蒋犁.妊娠期胆汁淤积症对新生儿中枢神经的影响[J].中国交通医学杂志[J],2004,18(6):720-721.
[3] Monte MJ,Morales Al,Arevalo M,el al.Reversible impairment of neonatal hepatobiliary function by maternal cholestasisl[J].J Hepatology, 1996,23(5): 1208-1217.
[4]丁依玲,付霞霏.妊娠肝内胆汁淤积症胎儿总胆汁酸浓度与肾上腺皮质功能变化的关系[J].中华围产医学杂志,2005,8(3):168-170.
[5] Gorelik J, Shevchuk A, Swiet M, et al. Comparison of the arrhythmogenic effects of tauro and glycoconjugates of cholicacid in an in vitro study of rat cardiomyocytes [J].BJOG, 2004,111(8):867-870.
[6]曹泽毅主编.中华妇产科学[M].第2版,北京:人民卫生出版社,2004:207.
[7]韦冰,车小群.胰岛素样生长因子Ⅰ、脐血瘦素及胰岛素与胎儿宫内发育迟缓的相关关系[J].河北医学,2006,12(9):845-847.
[8]卢青,时浩,毛鑫智等.妊娠大鼠胆酸负荷对母体和胎儿血清葡萄糖和激素水平及胎儿生长发育的影响[J].中国应用生理学杂志,1999,15(1):80-81.
[9]李新平,李静,陈龙等.胆酸负荷对妊娠母羊和胎儿的影响[J].实验动物与比较医学,2006,26(1):10-16.
[10]朱桂玉,左磊.妊娠胆汁淤积症对胎儿生长发育影响的研究[J].护理研究,2006,10(20):2685.
[11] Wang XD,Peng B,Yao Q,Zhang L,et al.Perinatal outcomes of intrahepatic cholestasis of pregnancy: analysis of 1210 cases[J].Zhonghua Yi Xue Za Zhi,2006,86(7):446-449.
[12] Sledge GW Jr.Vascular endothelial growth factor in breast cancer: biologic and therapeutic aspects[J].Semin Oncol,2002,29(3):104-110.
[13] Monte MJ,Rodrguez BT, Macias RIR,et al. Relationship between bile acidtransplacental gradients and transport across the fetal-facing plasma membrane of the human trophoblast[J].Pediatr Res,1995,38:156 -163.
[14]李华,曾蔚越.妊娠期肝内胆汁淤积症对母儿的危害[J].实用妇产科杂志,2002,18(1):829.
[15] Vyas S, Nico laides KH, Campbell S. Renal artery flow velocity ware farms in??normal and hypoxemia fetuses [J]. Am J Obstet Gynecol, 1989, 161(1): 168-169.
[16] Arrese M, Trauner M, Boyer JL, et al. Maternal Cholestasis does not affect the ontogenic pattern of expression of the Na~+/Taurocholate cotransporting polypeptide (ntcp) in the fetal and neonatal rat and neonatal rat liver[J]. Hepatology, 1998, 28(4):789-795.
[17]葛霞,李茂胜,赵连军,等.妊娠后期皮肤瘙痒、黄疸、新生儿窒息[J].临床与实验病理学杂志,1999,15:171-172.
[18] Williamson C,Gorelik J,Eaton BM,et al.The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric chotestasis[J].Clin Sci(Lond),2001,100:363-369.
[1] Costoya AL,Leontic EA,Rosenberg HG,et a 1.Morphological study of placental terminal villi in intrahepatic cholestasis of pregnancy : histochemistry,light and electronmicroscopy[J].Placenta, 1980,1:361-368.
[2] Xiao J P,Wang H Q,Guo H. Study of the ultrastructure and the expression of insulin-like growth factor I receptor in placenta with intrahepatic cholestasis of pregnancy [J]. Journal of Clinical Medicine in Practice, 2004, 8(5):47-48.
[3] Shao Y, Qi H, Zhang J H, et al.The effect fetal growth in intrahepatic cholestasis of pregnancy[J]. Journal of Chongqing Medical University, 2007, 32(1):69-71.
[4] Karr K,Jouppila P,Kuikka J,et al.Intervillous blood flow in normal and complicated late pregnancy measured by means of an intravenous 133Xe method[J].Aeta Obstet Gyneeol Scand,1980,59(1):7-10.
[5]刘伯宁,沈宁,陶雯琪,等.妊娠期肝内胆汁淤积症胎盘的组织计量测定[J].中华妇产科杂志,1988,23(2):9-12.
[6] Wang X D,Liu S Y,Heng Z C. Influence of placenta on fetal hypoxia in intrahepatic cholestasis of pregnancy [J]. Hua Xi Yi Ke Da Xue Xue Bao, 2002, 33(1):108-110, 114.
[7] Chen Z,Xu J J,Lu Y N.Expression of vascular endothelial growth factor in placenta in normal pregnancy and patients with intrahepatic cholestasis of pregnancy[J]. Chinese Journal of the Practical Chinese with Modem Medicine, 2004, 4(17): 1339-1341.
[8]秦惠芬,乔福元.胎盘生长因子及受体在妊娠肝内胆汁淤积症患者胎盘中的表??达及其意义[J].中国优生与遗传杂志,2006,14(3):33-35.
[9]王静波,常青,陈勇,等.妊娠肝内胆汁淤积症孕妇血清和脐血清一氧化氮变化及胎盘一氧化氮合酶的表达[J].第三军医大学学报,2005,27(18):1907-1908.
[10]李红霞,刘伯锋,姚珍薇,等.妊娠肝内胆汁淤积症患者胎盘中NPY的表达及意义[J].陕西医学杂志,2007,36(3):303-304.
[11] Chen J L,Liu S Y,Wang X D.study the excretion level of corticotrophin-releasing hormone from placenta tissue in patients with cholestasis during pregnancy[J]. West China Medical Journal, 2006, 21(2)262-263.
[12] Sepulveda WH,Gonzalez C,Cruz MA,et al.Vasoconstrictive effect of bile acids on isolated human placental chorionic veins[J].Eur J Obstet Gynecol Reprod Biol.1991,42:211-215.
[13]杨青,许建成,张红军,等.妊娠肝内胆汁淤积症患者GSH-PX、LPO、SOD水平及临床意义[J].中国妇幼保健,2006,21(8):1110-1111.
[14] Xiong G W,Wang J B,Lin C,et al.Level of Serum MDA and Vitamin E of Patients with Intrahepatic Cholestasis of Pregnancy[J].J Practic Obstet Gynecol,2005,22(5):303-305.
[15] Reyes H, Baez ME, Gonzalez MC, etal. Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals, in Chile[J] J Hepatol,2000,32(4):542-549.
[16]张婵,刘淑芸,杨开选.Fas和FasL在妊娠肝内胆汁淤积症患者胎盘绒毛组织中的表达及其意义[J].中华妇产科杂志2003,38(11):697-698.
[17] Balkundi DR,Hanna N,Hileb M,et al.Laborasseclated changes in Fu ligand expression and function in human phcenta[J].Pediatr R,2000,47(3): 301-308.
[18]艾瑛,刘淑芸.转化生长因子β_2对妊娠肝内胆汁淤积症患者胎盘组织分泌肿瘤坏死因子α及γ干扰素的影响[J].中华妇产科杂志,2004,39(5):322-325.
[19]代鸣,乔福元.转化生长因子β1及其受体1在妊娠肝内胆汁淤积症患者胎盘绒毛组织中的表达及其意义[J].中国优生与遗传杂志,2005,13(1):27-29.
[20]葛霞,李茂胜,赵连军,等.妊娠后期皮肤瘙痒、黄疸、新生儿窒息[J].临床与实验病理学杂志,1999,15:171-172.
[21] Shao Y, Yao Z W, Lu J, et al. Fetal rats arrhythmias in intrahepatic cholestasis of pregnancy. Journal of Chongqing Medical University, 2006, 31(2):236-239.
[22]肖建平.126例妊娠期肝内胆汁淤积症胎儿脐血心肌酶检测的临床分析[J].中??国妇产科临床杂志,2006,7(5):368-369.
[23]邵勇,姚珍薇,罗红霞,等.孕鼠肝内胆汁淤积症致胎鼠心肌细胞凋亡[J].基础医学与临床,2007,27(1):85-86.
[24] Shao Y,YAO Z W,Li H X,et al.Efects of intrahepatic cholestasis on hearts of pregnant rats and their fetus[J].J Clin Exp Pathol, 2005 ,21(6):706-709.
[25]刘静,蒋犁.妊娠期胆汁淤积症对新生儿中枢神经的影响[J].中国交通医学杂志[J],2004,18(6):720-72 1.
[26]吴荞,苏志红,连建华,等.妊娠期肝内胆汁淤积症与新生儿黄疸的关系[J].中国优生与遗传杂志,2006,14(10):7/107.
[27] Monte MJ, Morales Al, Arevalo M, el a 1.Reversible impairment of neonatal hepatobiliary function by maternal cholestasisl[J].J Hepatology, 1996,23(5): 1208-1217.
[28]王春芳,陈晓军,周光兴.妊娠肝内胆汁淤积症对胎鼠应激反应能力的影响及其意义的初步探讨[J].实验动物与比较医学,2007,27(1):48-52.
[29] Ding Y L, Fu X F.Relationship between the concentration of fetal total bile acid and fetal adrenocortical dysfunction in intrahepatic cholestasis of pregnancy[J].Chin J Perinat Med, 2005, 8(3):168-170.
[30]卢青,时浩,毛鑫智等.妊娠大鼠胆酸负荷对母体和胎儿血清葡萄糖和激素水平及胎儿生长发育的影响[J].中国应用生理学杂志,1999,15(1):80-81.
[31] Ma Z S, Wang X L, Wang Y X, et al.Study on the Relationship between Epidermal Growth Factor and Intrahepatic Cholestasis of Pregnancy [J]. Clinical Medicine, 2003, 23(4)6-7.
[32] Wang H Y, Jiang Y Q,Wang Z P,et al.Study of ultrastructure and expression of epidermal growth factor receptor in placenta in intrahepatic Cholestasis of pregnancy[J].Chi J Perinat Med, 2004, 7(6):339-342.
[33]陈其新,李新平,孙敬,等.胆酸负荷对妊娠母羊和胎儿血浆IGF-2营养物质水平的影响口[J].中国兽医学报,2001,21(3):274-277.
[34]陈其新,李新平,毛鑫智,等.围产期绵羊血浆胰岛素样生长因-1水平的动态变化及胆酸负荷对其的影响[J].中国畜牧杂志,200l,37(1):6-8.
[35]邵建芳,谢黎,李敦华.妊娠肝内胆汁淤积症孕妇营养摄入量调查[J].浙江预防医学,2005,17(11):41-42.
[36] Bhalla P.Agrawa D.Alterations in rat erythrocyte membrane due to hexachlorocyclohexane exposure[J]. Hum Exp Toxieol, 1998, 17:638.
[37]岳亚飞,刘朝阳,石紫云.妊娠期肝内胆汁淤积症围生儿缺氧机理的研究[J].中国优生与遗传杂志,2005,13(9):57-58.
[38]周静,汪秀娟,杨军文,等.妊娠肝内胆汁淤积症胎儿宫内缺氧的初步研究[J].皖南医学院学报,2004,23(2):109-111.