婴儿巨细胞病毒性肝炎血清及胆汁中表皮生长因子的变化及其发病机制研究

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目的研究婴儿巨细胞病毒性肝炎(ICH)血清及胆汁引流液中表皮生长因子(EGF)的水平变化及临床意义。方法收集南京市儿童医院2002年11月至2003年4月收治的巨细胞病毒(CMV)性肝炎患儿32例,根据血生化分为胆汁淤积型和肝炎型两组,对照组13例来自同期住院的无消化、呼吸系统疾病的患者,排除宫内感染史,分别收集血和十二指肠引流液标本,采用放免法检测标本中EGF、透明质酸(HA)、Ⅳ型胶原(4-C)含量,并分析其与临床资料之间的相关性。结果(1)肝炎组、淤胆组、对照组中血清中EGF含量分别为(0.52±0.14)、(2.01±1.17)、(0.59±0.40)μg/L,HA含量分别为(293.85±196.02)、(608.68±268.48)和(183.27±106.31)ng/L,IV型胶原含量分别为(96.90±37.34)、(367.17±200.36)和(78.30±9.35)ng/L;十二指肠引流液中EGF含量分别为(15.93±7.64)、(6.94±3.76)、(2.75±0.40)μg/L,HA含量分别为(1402.13±439.17)、(1896.61±232.32)和(1411.12±332.26)ng/L,IV型胶原含量分别为(323.24±292.28)、(655.78±320.17)和(128.39±86.64)ng/L。(2)所有观察对象中EGF在十二指肠引流液中浓度显著高于血清中浓度(P<0.01)。(3)肝炎组和淤胆组患儿十二指肠引流液EGF浓度显著高于对照组(P<0.01和P<0.05),且和血清中ALT水平正相关,肝炎组十二指肠液中EGF浓度显著高于淤胆组(P<0.05)。(4)淤胆组血清EGF水平显著高于肝炎组和对照组(P<0.01),而肝炎组和对照组之间则差异无显著性。(5)淤胆组血清中HA和4-C含量较肝炎组和对照组均有显著性升高(P<0.01),十二指肠引流液中HA和4-C含量较肝炎组和对照组亦有显著性升高(P<0.05),而肝炎组和对照组之间在血清和胆汁引流液中HA和4-C含量比较上无显著性差异。结论(1)CMV感染可使局部EGF释放增加,肝胆组织中分泌的EGF通过胆道系统排泄,故胆汁引流液中EGF水平是一项反映肝胆炎性损伤程度及胆管排泄有无梗阻的综合性指标,小婴儿行十二指肠引流是安全可行的。(2)血清中持续的EGF高水平状态可通过促进肝间质细胞增生而产生胶原纤维,从而促进肝纤维化的发展,婴儿CMV肝炎淤胆型易早期形成肝纤维增生。 Objective To study the changes and clinical significance of epidermal growth factor (EGF) levels in sera of infants with cytomegalovirus (ICH) and bile drainage. Methods Thirty-two children with cytomegalovirus (CMV) hepatitis treated at Nanjing Children’s Hospital from November 2002 to April 2003 were divided into two groups: cholestatic type and hepatitis type according to blood biochemistry. Thirteen patients in control group Inpatients with non-digestive and respiratory diseases were excluded from the history of intrauterine infection. Blood and duodenal drainage fluid samples were collected. The levels of EGF, hyaluronic acid (HA), type Ⅳ collagen (4- C) content, and analyze the correlation with clinical data. Results The serum levels of EGF in hepatitis group, cholestasis group and control group were (0.52 ± 0.14), (2.01 ± 1.17) and (0.59 ± 0.40) μg / L, respectively. The contents of HA were (293.85 ± 196.02) , (608.68 ± 268.48) and (183.27 ± 106.31) ng / L respectively, and the type IV collagen contents were 96.90 ± 37.34, 367.17 ± 200.36 and 78.30 ± 9.35 ng / L, respectively. The levels of EGF were (15.93 ± 7.64), (6.94 ± 3.76) and (2.75 ± 0.40) μg / L, respectively. The content of HA was (1402.13 ± 439.17), (1896.61 ± 232.32) and (1411.12 ± 332.26) ng / Type IV collagen content was (323.24 ± 292.28), (655.78 ± 320.17) and (128.39 ± 86.64) ng / L, respectively. (2) The EGF concentration in duodenal drainage fluid in all the subjects was significantly higher than that in serum (P <0.01). (3) The EGF concentration of duodenal drainage fluid in hepatitis group and cholestasis group was significantly higher than that in control group (P <0.01 and P <0.05), and positively correlated with serum ALT level. In duodenal fluid of hepatitis group EGF concentration was significantly higher than the cholestasis group (P <0.05). (4) The levels of serum EGF in cholestasis group were significantly higher than those in hepatitis group and control group (P <0.01), but there was no significant difference between hepatitis group and control group. (5) The contents of HA and 4-C in serum of cholestasis group were significantly higher than those in hepatitis group and control group (P <0.01). The contents of HA and 4-C in duodenal drainage fluid were significantly higher than those in hepatitis group and control group Group (P <0.05). There was no significant difference in the content of HA and 4-C in serum and bile drainage between hepatitis and control group. Conclusion (1) CMV infection can increase local EGF release, secretion of EGF in hepatobiliary tissue excretion through the biliary system, so the level of EGF in biliary drainage fluid is a reflection of the degree of hepatobiliary inflammation and bile duct excretion with or without obstruction of a comprehensive index Small infants duodenal drainage is safe and feasible. (2) The sustained high level of EGF in serum can produce collagen fibers by promoting the proliferation of hepatic interstitial cells, thus promoting the development of hepatic fibrosis. Infantile cholestasis of CMV is easy to form hepatic fibrosis in early stage.
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