母源外周血中IL-6表达水平与乙型肝炎病毒宫内传播的关系

王海荣; 邵昱璋; 李芳; 严敏; 付婷; 张磊

doi:10.16462/j.cnki.zhjbkz.2020.05.018

母源外周血中IL-6表达水平与乙型肝炎病毒宫内传播的关系

doi: 10.16462/j.cnki.zhjbkz.2020.05.018

王海荣¹,
邵昱璋²,
李芳³,
严敏¹,
付婷¹,
张磊^1, ,

1.
710032 西安, 空军军医大学军事预防医学系流行病学教研室特殊作业环境危害评估与防治教育部重点实验室
2.
710061 西安, 西安交通大学医学院
3.
710061 西安, 西北妇女儿童医院

基金项目: 国家自然科学基金(81102140、81472988、81373058);国家重点研发计划(2016YFC1303204);国家级科技部重大专项(2017ZX0105011)

详细信息

通讯作者:
张磊, E-mail:drzhanglei@fmmu.edu.cn

中图分类号: R181.2
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出版历程
- 收稿日期: 2019-09-29
- 修回日期: 2020-01-22
- 刊出日期: 2020-05-10

Relationship study between the IL-6 expression in maternal peripheral blood and intrauterine transmission of HBV

1.
Department of Epidemiology, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Military Preventive Medicine, Air Force Military Medical University, Xi'an 710032, China
2.
Xi'an Jiaotong University(Medical College), Xi'an 710061, China
3.
Northwest Women and Children Hospital, Xi'an 710061, China

Funds: National Natural Science Foundation of China(81102140, 81472988, 81373058); National Key R & D Program of China(2016YFC1303204); Major National Special Project for Prevention and Control of Infectious Diseases(2017ZX0105011)

More Information

Corresponding author: ZHANG Lei, E-mail:drzhanglei@fmmu.edu.cn

摘要

摘要: 目的探讨HBsAg阳性产妇外周血IL-6水平在乙型肝炎病毒(hepatitis B virus, HBV)宫内传播中的表达变化。方法以陕西省西北妇女儿童医院住院分娩的314例HBsAg阳性产妇为病例组, 74例健康产妇为对照组进行流行病学调查, 采用ELISA法检测孕妇和新生儿外周血乙型肝炎5项指标, 采用实时荧光定量PCR检测HBV-DNA水平, 采用流式液相芯片法检测细胞因子IL-6水平。结果 HBsAg阳性产妇发生宫内显性感染(dominant HBV infection, DBI)、宫内隐匿性感染(occult hepatitis B virus infection, OBI)和宫内传播(intrauterine transmission, BIT)率为10.83%(34/314)、38.22%(120/314)、49.04%(154/314)。对照组产妇IL-6水平低于HBsAg阳性产妇组(P < 0.001)、NBIT组(P < 0.001)、DBI组(P=0.006)和OBI组(P < 0.001);未抗病毒治疗组中DBI组IL-6水平低于OBI组(P=0.008);未乙肝疫苗注射组中DBI组IL-6水平低于OBI组(P=0.012);产妇HBeAg和HBV DNA载量与其IL-6水平呈正相关(均有P < 0.05);产妇HBeAb与IL-6水平呈负相关(P=0.011)。结论 HBV可以激发孕产妇体内IL-6的表达, 但是IL-6在HBsAg阳性产妇体内的表达呈现组内分化现象, 在HBeAg阳性和高载量HBV DNA环境下其IL-6的水平会上升, 但当其水平下降时易发生DBI。
- 乙型肝炎病毒 /
- 宫内传播 /
- 显性感染 /
- 隐匿性感染 /
- 白介素6
Abstract: Objective To investigate the expression of IL-6 in peripheral blood of HBsAg positive parturients in HBV intrauterine transmission. Methods Epidemiological investigation was carried out on 314 HBsAg positive parturients delivered in Northwest Women and Children's Hospital of Shaanxi Province and 74 health parturientsas control group. Enzyme-linked immunosorbent assay(ELISA) was used to detect five makers of hepatitis B, real time PCR was used to detect HBV-DNA, and flow liquid chip method was used to detect IL-6 in peripheral blood of pregnant women and newborns. Results The incidence of dominant HBV infection(DBI), occult HBV infection(OBI) and BIT were 10.83%(34/314), 38.22%(120/314), 49.04%(154/314), respectively. The levels of IL-6 in peripheral blood of HBsAg-negative parturients were significantly lower than those of HBsAg-positive parturients(P < 0.001), NBIT group(P < 0.001), DBI group(P=0.006), OBI group(P < 0.001). In the antiviral treatment group, the level of IL-6 in DBI group was significantly lower than OBI group(P=0.008).In non-hepatitis B vaccine group, the level of IL-6 in DBI group was significantly lower than OBI group(P=0.012). The level of maternal IL-6 have positive relation to the maternal HBeAg status and HBV DNA load in maternal blood(all P < 0.05).The level of maternal IL-6 have negative relation to the maternal HBeAb status in maternal blood(P=0.011). Conclusions HBV can stimulate the expression of IL-6 in pregnant and lying-in women, but the expression of IL-6 in HBsAg-positive parturients shows intra-group differentiation. The level of IL-6 in maternal will increase in HBeAg-positive and HBV DNA high-load environment. DBI is prone to occur when IL-6 level decreases.
- Hepatitis B virus(HBV) /
- Intrauterine transmission /
- Apparent infection /
- Occult infection /
- Interleukin 6

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表 1 产妇及其新生儿基础特征

Table 1. Basic characteristics of parturient and newborns

指标	产妇HBsAg阳性组	产妇HBsAg阴性组	t /χ²值	P值
产妇	314	74
年龄(岁, x±s)	30±3.8	29±4.5	1.730^a	0.087
有孕产史[n(%)]	135(43.0)	32(43.2)	0.002	0.969
第一胎[n(%)]	179(57.0)	42(56.8)	0.002	0.969
新生儿	314	74
男婴[n(%)]	150(47.8)	36(48.6)	0.018	0.892
顺产[n(%)]	168(53.5)	39(52.7)	0.015	0.901
早产[n(%)]	6(1.9)	2(3.0)	< 0.001^b	1.000
注:^a表示t值; ^b表示校正χ²值

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表 2 HBsAg阴性与HBsAg阳性产妇各宫内传播组IL-6水平情况

Table 2. Comparison of the level of IL-6 between HBsAg negative and HBsAg position parturients

产妇分组	例数	IL-6 (pg/ml)	HBsAg阴性组比HBsAg阳性各组		NBIT组比BIT、OBI、DBI组		OBI组比DBI组
产妇分组	例数	IL-6 (pg/ml)	U值	P值	U值	P值	U值	P值
HBsAg阴性	74	12(150.77, 89.54)^a	—	—	—	—	—	—
HBsAg阳性	314	42.02(15.09, 139.55)^a	7 058.50	< 0.001	—	—	—	—
NBIT	160	44.95(15.75, 139.55)^a	3 497.50	< 0.001	—	—	—	—
BIT	154	40.3(14.76, 136.96)^a	3 561.00	< 0.001	11 856.50	0.564	—	—
OBI	120	180.44±378.42^b	2 719.50	< 0.001	9 425.00	0.794	—	—
DBI	34	38.32(16.42, 120.95)^a	8 41.50	0.006	2 431.50	0.332	1 843.00	0.391
注:^a表示M(P₂₅, P₇₅); ^b表示(x±s); DBI:HBV宫内显性感染; OBI:HBV宫内隐匿性感染; BIT:HBV宫内传播; NBIT:HBV宫内未传播。

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表 3 HBsAg阳性产妇不同HBV感染状态下的IL-6水平对比

Table 3. 3 Comparison of the level of IL-6 in different infection status of HBsAg position parturients

指标	例数(n)	DBI	OBI	NBIT	合计	3组总体比较
指标	例数(n)	DBI	OBI	NBIT	合计	χ²值	P值
HBeAg
阴性	227	28.20 (10.01, 81.81)	40.03 (13.57, 170.71)	185.84±607.80	179.36±516.09	2.05	0.359
阳性	87	44.95 (17.70, 132.71)	42.43 (14.76, 129.41)	57.71 (19.27, 166.42)	170.86±344.32	1.16	0.560
t/U值		105.000	1 443.500	1866.000	0.140
P值		0.174	0.799	0.184	0.887
HBV DNA(IU/ml)
﹤10³	194	37.76 (15.20, 136.09)	212.34±394.86	183.96±644.06	188.87±540.64	1.79	0.409
10³ ~	60	31.39 (8.53, 45.34)	22.37 (9.88, 139.55)	254.44±471.44	205.47±444.01	2.25	0.325
> 10 ⁶	60	79.99±155.87	180.07±248.67	108.52 (18.65, 257.21)	110.17±184.45	4.02	0.134
χ²		0.814	4.380	1.980	0.983
P值		0.666	0.112	0.371	0.612
注:小括号内为例数; DBI:HBV宫内显性感染; OBI:HBV宫内隐匿性感染; NBIT:HBV宫内未传播; χ²为采用K-W检验对各状态分组中DBI、OBI、NBIT3组比较, 以及DBI、OBI、NBIT在不同HBV DNA载量中3组比较。

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表 4 HBsAg阳性产妇孕期不同干预因素下IL-6水平的对比

Table 4. Comparison of the level of IL-6 in HBsAg position parturients with different treatment

指标	例数(n)	DBI	OBI	NBIT	合计	3组总体比较
指标	例数(n)	DBI	OBI	NBIT	合计	χ²值	P值
抗病毒
治疗	52	59.19±53.49	108.94±188.66	185.46±321.51	147.79±267.33	0.90	0.639
阳性未治疗	262	74.12±102.22	193.89±403.55	199.14±618.36	182.80±505.52	1.05	0.592
U/t值		-0.280	-0.900	-0.120	-0.490
P值		0.778	0.372	0.908	0.627
乙肝疫苗
注射	35	16.83 (2.32, 136.09)	41.32 (10.57-158.40)	25.94 (13.99, 200.81)	26.46(13.99, 146.75)	1.07	0.587
未注射	265	78.91±105.16	196.43±410.65	178.58±575.15	175.41±489.40	0.137	0.934
U/t值		68.500	741.000	775.000	4 152.500
P值		0.322	0.726	0.630	0.315
HBIG
注射	98	61.61 (17.60, 135.25)	41.23 (9.87, 106.80)	64.02 (14.90, 168.57)	49.08 (14.57, 136.96)	1.96	0.375
未注射	210	37.62 (16.02, 62.44)	43.36(14.76, 188.89)	134.57±259.40	40.03 (15.55, 139.55)	1.48	0.477
U值		96.500	1 471.000	2 155.000	10 210.000
P值		0.270	0.274	0.380	0.912
注:DBI组、OBI组和NBIT组进行两两比较, 抗病毒未治疗组和乙肝疫苗未注射组中DBI组与OBI组比较差异均有统计学意义(P < 0.05), 其他各组分组间差异无统计学意义(均有P > 0.05)。

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表 5 产妇IL-6水平与HBV宫内传播的多因素Logistic回归分析

Table 5. Multivariatelogistic regression analysis of the parturients level of IL-6 and HBV BIT

HBV宫内传播分组	变量	β值	S_x	Wals	P值	OR值	OR值的95%置信区间
HBV宫内传播分组	变量	β值	S_x	Wals	P值	OR值	下限	上限
NBIT和DBI	产妇HBeAg	1.273	0.393	10.507	0.001	3.571	1.654	7.711
	产妇HBeAb	-0.976	0.386	6.394	0.011	0.377	0.177	0.803
	HBV DNA≥10³	1.957	0.463	17.865	0.000	7.078	2.856	17.539
OBI和DBI	产妇HBeAg	0.887	0.397	4.983	0.026	2.429	1.114	5.293
	产妇HBeAb	-0.693	0.395	3.085	0.079	0.500	0.231	1.084
	HBV DNA≥10³	1.436	0.461	9.695	0.002	4.205	1.703	10.383

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