Th1/Th2平衡偏移在苯并[a]芘宫内暴露与胚胎停育关联中的中介效应

李福星; 刘莎; 张嘉宇; 籍静茹; 武嫣斐; 曹九茹; 魏俊妮

doi:10.16462/j.cnki.zhjbkz.2024.11.004

Th1/Th2平衡偏移在苯并[a]芘宫内暴露与胚胎停育关联中的中介效应

doi: 10.16462/j.cnki.zhjbkz.2024.11.004

1.
山西医科大学公共卫生学院流行病学教研室，太原 030001
2.
山西医科大学第一医院产科，太原 030001

基金项目:

山西省应用基础研究项目 201901D111206

山西省卫生健康委科研计划项目 2020086

详细信息

通讯作者:
魏俊妮，E-mail: junni.wei@sxmu.edu.cn

中图分类号: R714.21
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出版历程
- 收稿日期: 2023-11-03
- 修回日期: 2024-04-18
- 网络出版日期: 2024-12-23
- 刊出日期: 2024-11-10

The mediating effect of Th1/Th2 balance deviation in the association between B[a]P intrauterine exposure and embryonic arrest

1.
Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China
2.
Department of Obstetrics, The First Hospital of Shanxi Medical University, Taiyuan 030001, China

Funds:

Shanxi Provincial Basic Research Project 201901D111206

Shanxi Provincial Health Commission Scientific Research Project 2020086

More Information

Corresponding author: WEI Junni, E-mail: junni.wei@sxmu.edu.cn

摘要

摘要: 目的探讨苯并[a]芘(benzo [a] pyrene, B[a]P)宫内暴露与胚胎停育的关联，以及辅助性T细胞1/ 辅助性T细胞2(helper T cell 1/ helper T cell 2, Th1/Th2)平衡偏移的中介效应。方法选取胚胎停育患者与正常妊娠但自愿人工流产的女性作为研究对象(245名)。检测研究对象绒毛组织中7, 8-二羟-9, 10-环氧苯并[a]芘(7, 8-dihydroxy-9, 10-epoxy-benzo [a] pyrene, BPDE)-DNA加合物与白细胞介素(interleukin, IL)-2、干扰素-γ(interferon-γ, IFN-γ)、IL-4、IL-10水平。采用logistic回归分析模型分析B[a]P暴露与胚胎停育的关联，运用Bootstrap法分析Th1/Th2平衡偏移的中介效应。结果调整协变量后，BPDE-DNA加合物的中高暴露、高暴露水平发生胚胎停育的风险分别是低暴露水平的5.66倍(aOR=5.66, 95% CI: 2.00~16.01, P < 0.001)、5.63倍(aOR=5.63, 95% CI: 1.97~16.14, P < 0.001)；中介分析结果显示，B[a]P对胚胎停育的总效应为1.220(0.501~1.939)，Th1/Th2平衡偏移介导的中介效应为0.328(0.078~0.716)，中介比例占26.89%。结论 B[a]P暴露是胚胎停育的危险因素，且Th1/Th2失衡发生Th1型偏移是B[a]P暴露致胚胎停育的中介变量。
- 苯并[a]芘 /
- 胚胎停育 /
- 辅助性T细胞1/辅助性T细胞2 /
- 平衡偏移 /
- 中介效应
Abstract: Objective To investigate the association between exposure to benzo [a] pyrene (B[a]P) and embryonic arrest, and the mediating effects of helper T cell 1/helper T cell 2(Th1/Th2) balance deviation. Methods A total of 245 women with embryonic arrest and women with normal pregnancy who voluntarily induced abortion were selected as the study objects. The levels of 7, 8-dihydroxy-9, 10-epoxy-benzo [a] pyrene (BPDE)-DNA adducts and interleukin (IL)-2, interferon-γ(IFN-γ), IL-4, IL-10 in villus tissues were detected. Logistic regression model was used to analyze the correlation between B[a]P exposure and embryonic arrest, and Bootstrap method was used to analyze the mediating effect of Th1/Th2 balance deviation between them. Results After adjusting for covariates, it was found that the risk of embryonic arrest at medium-high exposure level and high exposure level of BPDE-DNA adducts was 5.66 times (aOR=5.66, 95% CI: 2.00-16.01, P < 0.001) and 5.63 times(aOR=5.63, 95% CI: 1.97-16.14, P < 0.001) higher than that at low exposure level, respectively; The results of mediating analysis showed that B[a]P had a total effect of 1.220 (0.501-1.939) on embryonic arrest, with a mediating effect caused by Th1/Th2 balance deviation of 0.328 (0.078-0.716), accounting for 26.89%. Conclusions B[a]P exposure is a risk factor for embryonic arrest, and Th1/Th2 imbalance occurring with a Th1-Type deviation is a mediating variable of embryonic arrest caused by B[a]P exposure.
- Benzo [a] pyrene /
- Embryonic arrest /
- Helper T cell 1/helper T cell 2 /
- Balance deviation /
- Mediating effect

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图 1 B[a]P暴露致胚胎停育过程的直接与中介效应

图中c、c′、a、b均为方程参数。c，B[a]P→胚胎停育的总回归系数；c′，B[a]P→胚胎停育的直接回归系数；a，B[a]P→Th1/Th2的回归系数：b，Th1/Th2→胚胎停育的回归系数。中介效应＝a×b；B[a]P，苯并[a]芘；Th1/Th2，辅助性T细胞1/辅助性T细胞2。

Figure 1. The direct and mediating effects of B [a] P exposure on embryonic arrest

c, c′, a, and b are parameters of the equation. c is the total regression coefficient of B[a]P→embryonic arrest; c′ is the direct regression coefficient of B[a]P→embryonic arrest; a is the regression coefficient of B[a]P→Th1/Th2; b is the regression coefficient of Th1/Th2→embryonic arrest. Mediating effect＝a×b; B[a]P, benzo [a] pyrene; Th1/Th2, helper T cell 1/helper T cell 2.

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表 1 研究对象的一般特征

Table 1. General characteristics of participants

变量 Variable	病例组 Case group^① (n=110)	对照组 Control group^① (n=135)	t/χ²/Z值value	P值 value
年龄/岁 Age/years	30.71±5.05	29.31±6.09	1.93	0.055
孕周/周 Gestational age/weeks	9.11±1.61	7.15±0.97	11.79	< 0.001
户籍 Household registration			0.12	0.798
农村 Rural	47(42.73)	62(45.93)
城市 Urban	63(57.27)	73(54.07)
文化程度 Educational level			2.94	0.401
初中及以下 Junior high school or below	20(18.18)	16(11.85)
高中或中专 High school or technical secondary school	12(10.91)	22(16.30)
大专或大学 Junior college or university	63(57.27)	79(58.52)
研究生及以上 Postgraduate and above	15(13.64)	18(13.33)
家庭人均月收入/元 Monthly income per capita/yuan			8.78	0.067
< 2 000	4(3.64)	13(9.63)
2 000~ < 3 000	23(20.91)	30(22.22)
3 000~ < 5 000	29(26.36)	37(27.41)
5 000~ < 10 000	48(43.64)	40(29.63)
≥10 000	6(5.45)	15(11.11)
怀孕次数 Number of pregnancies			5.04	0.800
1	48(43.64)	42(31.11)
2	31(28.18)	39(28.89)
≥3	31(28.18)	54(40.00)
痛经 Dysmenorrhea			1.01	0.356
是 Yes	46(41.82)	48(35.56)
否 No	64(58.18)	87(64.44)
不良妊娠史 Adverse pregnancy history			11.96	< 0.001
是 Yes	38(34.55)	21(15.56)
否 No	72(65.45)	114(84.44)
既往病史 Previous medical history			0.01	0.930
是 Yes	6(5.45)	6(4.44)
否 No	104(94.55)	129(95.56)
定期体检 Regular physical examination			0.16	0.699
是 Yes	67(60.91)	79(58.52)
否 No	43(39.09)	56(41.48)
孕前服用避孕药 Usage of contraception pill			0.38	0.610
是 Yes	6(5.45)	10(7.41)
否 No	104(94.55)	125(92.59)
孕期吸烟 Smoking during pregnancy			1.60	0.205
是 Yes	1(0.91)	6(4.44)
否 No	109(99.09)	129(95.56)
孕期饮酒 Drinking during pregnancy			2.02	0.234
是 Yes	3(2.71)	9(6.67)
否 No	107(97.27)	126(93.33)
孕期熬夜 Staying up late during pregnancy			0.40	0.898
是 Yes	54(49.09)	68(50.37)
否 No	56(50.91)	67(49.63)
BPDE-DNA加合物BPDE-DNA adduct/(pg·mL^-1)	292.72(262.44, 331.07)	254.69(225.24, 292.69)	-5.53	< 0.001
注：BPDE，7, 8-二羟-9, 10-环氧苯并[a]芘。 ①以x±s、M(P₂₅, P₇₅)或人数(占比/%)表示。 Note: BPDE, 7, 8-dihydroxy-9, 10-epoxy-benzo [a] pyrene. ① x±s, M(P₂₅, P₇₅) or number of people (proportion/%).

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表 2 BPDE-DNA加合物水平与胚胎停育的logistic回归分析

Table 2. Logistic regression analysis of BPDE-DNA adduct level and embryonic arrest

分组 Group	病例组 Case group^①	对照组 Control group^①	OR值value (95% CI)	P值 value	aOR值value (95% CI)	P值 value
T1	11(10.00)	50(37.04)	1.00		1.00
T2	25(22.73)	36(26.67)	3.16(1.38~7.23)	0.007	2.31(0.82~6.51)	0.112
T3	35(31.82)	27(20.00)	5.89(2.59~13.43)	< 0.001	5.66(2.00~16.01)	< 0.001
T4	39(35.45)	22(16.30)	8.06(3.49~18.59)	< 0.001	5.63(1.97~16.14)	< 0.001
注：aOR，调整年龄、孕周、户籍、文化程度、家庭人均月收入、孕次、痛经、不良妊娠史、既往病史、定期体检、孕前服用避孕药、吸烟、饮酒、熬夜后多因素logistic回归分析模型分析的OR值。 ①以人数(占比/%)表示。 Note: aOR, OR value of multivariate logistic regression analysis adjusted for age, gestational age, household registration, education level, monthly income per capita, number of pregnancies, dysmenorrhea, adverse pregnancy history, previous medical history, regular physical examination, usage of contraception pill, smoking, drinking and staying up late. ①Number of people (proportion/%).

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表 3 生物指标检出情况以及与胚胎停育的logistic回归分析

Table 3. The detection of biological indicators and logistic regression analysis of correlation with embryonic arrest

分组 Group	病例组 Case group^①	对照组 Control group^①	t值 value	P值 value	aOR值value (95% CI)	P值 value
IL-2/(pg·mL^-1)	697.26±67.57	650.27±54.97	5.88	< 0.001	1.02(1.01~1.03)	< 0.001
IFN-γ/(pg·mL^-1)	772.49±70.40	709.40±57.70	7.71	< 0.001	1.02(1.01~1.03)	< 0.001
IL-4/(pg·mL^-1)	46.49±4.24	47.36±3.93	-1.66	0.098	0.90(0.80~1.02)	0.096
IL-10/(pg·mL^-1)	770.38±47.88	827.96±135.75	-4.59	< 0.001	0.99(0.99~1.00)	0.018
Th1/Th2	1.80±0.15	1.59±0.26	8.04	< 0.001	8.20(3.69~18.23)	< 0.001
注：IL，白细胞介素；IFN-γ，干扰素-γ；Th1/Th2，辅助性T细胞1/辅助性T细胞2；aOR，调整年龄、孕周、户籍、文化程度、家庭人均月收入、孕次、痛经、不良妊娠史、既往病史、定期体检、孕前服用避孕药、吸烟、饮酒、熬夜后多因素logistic回归分析模型分析的OR值。 ①以x±s表示。 Note: IL, interleukin; IFN-γ, interferon-γ; Th1/Th2, helper T cell 1/helper T cell 2; aOR, OR value of multivariate logistic regression analysis adjusted for age, gestational age, household registration, education level, monthly income per capita, number of pregnancies, dysmenorrhea, adverse pregnancy history, previous medical history, regular physical examination, usage of contraception pill, smoking, drinking and staying up late. ① x±s.

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表 4 BPDE-DNA加合物水平与各细胞因子及Th1/Th2比值的关系

Table 4. The relationship between BPDE-DNA adducts level and cytokines and Th1 /Th2 ratio

变量 Variable	b值 value(95% CI)	s_x值 value	β值 value	t值 value	P值 value
IL-2	-3.39(-11.95~5.17)	4.35	-0.06	-0.78	0.436
IFN-γ	10.32(2.42~18.22)	4.01	0.16	2.57	0.011
IL-4	0.03(-0.53~0.59)	0.28	0.01	0.11	0.914
IL-10	-20.87(-32.70~-9.03)	6.01	-0.21	-3.47	< 0.001
Th1/Th2	0.05(0.02~0.07)	0.01	0.21	3.38	< 0.001
注：IL，白细胞介素；IFN-γ，干扰素-γ；Th1/Th2，辅助性T细胞1/辅助性T细胞2。 Note: IL, interleukin; IFN-γ, interferon-γ; Th1/Th2, helper T cell 1/helper T cell 2.

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