Ala-Gln增强机体在全胃肠外营养状态下对失血性休克的耐受性

采用ＳＰＦ大鼠全胃肠外营养（ＴＰＮ）支持和失血性休克创伤模型，以ＴＰＮ、ＴＰＮ液中添加丙氨酰谷氨酰胺（Ａｌａ┐Ｇｌｎ）和经肠饮食（ＥＮ）三种营养方式支持一周后，造成失血性休克，观察机体因营养方式差异而处于不同肠屏障功能状态下对再次打击的耐受性。结果显示，标准ＴＰＮ组与ＥＮ相比，血浆二胺氧化酶（ＤＡＯ）水平明显低下；肠固有层（ＬＰ）淋巴细胞和浆细胞、肠上皮内淋巴细胞（ＩＥＬ）及肠腔细菌分泌型ＩｇＡ（Ｓ┐ＩｇＡ）包被率明显下降；盲肠粘膜菌群Ｅ．ｃｏｌｉ优势增殖，双歧杆菌／大肠杆菌（Ｂ／Ｅ）比值倒置，肠上皮细菌粘附增多；肠道细菌易位率升高；死亡率（４／１２）高。而Ａｌａ┐Ｇｌｎ组因添加肠道必需氨基酸谷氨酰胺（Ｇｌｎ）前体Ａｌａ┐Ｇｌｎ，各参数接近ＥＮ组，肠屏障储备增加，死亡率下降。提示：标准ＴＰＮ由于缺乏肠粘膜必需氨基酸（Ｇｌｎ）和肠道刺激，严重损伤肠屏障功能，失血性休克更加重损害，可能促发脓毒血症和多器官功能不全（ＭＯＤＳ）。对标准ＴＰＮ进行改良，添加肠粘膜保护剂Ａｌａ┐Ｇｌｎ对肠屏障有较好维持作用。这对临床不能经肠道喂养的围手术期病人进行如何更有效的肠外营养支持有一定指导意义     

鱼油对感染大鼠肠粘膜的保护作用

目的：探讨膳食鱼油对感染机体小肠粘膜的保护作用。方法：将大鼠随机分为ＮＳ＋ＣＬＰ，ＦＯ＋ＣＬＰ及ＳＨＡＭ（假手术）三组（ｎ＝１５），术前分别灌食鱼油或等渗盐水１ｍｌ×３周，于ＣＬＰ后第二天采取标本检测血清ＴＮＦ、ＩＬ┐６、ＰＧＥ２浓度及小肠谷氨酰胺（Ｇｌｎ）含量，并用ＲＴ┐ＰＣＲ方法测定小肠粘膜ＴＮＦｍＲＮＡ的含量。结果：ＮＳ＋ＣＬＰ组大鼠血清ＴＮＦ、ＩＬ┐６、ＰＧＥ２水平明显高于ＳＨＡＭ组（Ｐ＜０．０１），小肠粘膜Ｇｌｎ含量显著减少（０．２８±０．１１ｖｓ０．９９±０．２１，Ｐ＜０．０１），而ＴＮＦｍＲＮＡ表达显著升高（Ｐ＜０．０１）。与之相比，灌食ＦＯ大鼠血清ＴＮＦ、ＩＬ┐６、ＰＧＥ２水平则有不同程度的下降，而小肠粘膜Ｇｌｎ含量明显高于ＮＳ＋ＣＬＰ组，同时，小肠粘膜ＴＮＦｍＲＮＡ的表达显著降低（Ｐ＜０．０１）。结论：鱼油能通过抑制花生四烯酸代谢产物的生成，改善小肠粘膜的血循环，或降低粘膜局部细胞因子的表达，阻断细胞因子对肠粘膜结构功能及细胞代谢的不利影响     

干扰素治疗丙型肝炎疗效相关因素分析

目的：探讨预测干扰素治疗慢性丙型肝炎（ＣＨＣ）疗效的临床上适用、简便、易行的指标。方法：对采用干扰素（ＩＦＮα－１ｂ）治疗３２例ＣＨＣ临床资料进行观察,包括治疗前后肝功能（ＡＬＴ、ＳＢ、ＧＧＴ）、抗－ＨＣＶＯＤ水平、ＨＣＶ基因型、ＨＣＶＲＮＡ、ＳＩＬ－２Ｒ、β２－ＭＧ等,治疗结束时有效者为肝功能复常同时ＨＣＶＲＮＡ阴转,其余反应模式均为无效者。结果：ＨＣＶ基因型为Ⅲ型患者疗效（５／１０）明显高于Ⅱ型（２／１９）（Ｐ＜０．０５）,有效者治疗前血清抗—ＨＣＶＯＤ明显低于无效者（Ｐ＜０．０５）,治疗后有效者β２－ＭＧ升高水平（３．４５±１．０８）ｍｇ／Ｌ明显高于无效者（１．３３±０．９５）ｍｇ／Ｌ（Ｐ＜０．０５）,而两者治疗前ＡＬＴ、ＳＢ、ＧＧＴ、ＩｇＭ、β２－ＭＧ患者的年龄无明显差别（Ｐ＞０．０５）。结论：感染ＨＣＶ基因型,治疗前抗—ＨＣＶＯＤ水平及治疗后β２－ＭＧ变化对预测ＩＦＮ治疗ＣＨＣ疗效有一定参考价值。     

脱氧雪腐镰刀菌烯醇、黄曲霉毒素G_1对体外培养人外周血淋巴细胞凋亡影响的研究

以细胞培养、流式细胞仪ＤＮＡ含量分析及ＤＮＡ琼脂糖凝胶电泳方法研究了我国食管癌高发区磁县居民粮食中优势污染霉菌毒素脱氧雪腐镰刀菌烯醇（ＤＯＮ）和黄曲霉毒素Ｇ１（ＡＦＧ１）对人淋巴细胞凋亡的影响。流式细胞术（ＦＣＭ）检测结果显示,ＤＯＮ、ＡＦＧ１处理组淋巴细胞出现了典型的亚二倍体凋亡细胞峰,凋亡百分率与毒素作用时间（ＤＯＮ：２～７２小时;ＡＦＧ１：２～２４小时）及剂量（ＤＯＮ：５０～２０００μｇ／Ｌ;ＡＦＧ１：３．１２～２０００μｇ／Ｌ）呈正相关关系。ＤＮＡ琼脂糖凝胶电泳结果表明,ＤＯＮ（１０００μｇ／Ｌ）、ＡＦＧ１（１０００μｇ／Ｌ）处理２４小时淋巴细胞出现特征性的ＤＮＡ＂Ｌａｄｄｅｒ＂条带。因此表明,ＤＯＮ、ＡＦＧ１可诱导和促进体外培养的人外周血淋巴细胞发生凋亡。     

脂质过氧化物及超氧化物歧化酶在肾小球疾病中的临床观察

本研究测定了２５例原发性肾病综合征（ＰＮＳ）、１５例急性肾小球肾炎（ＡＧＮ）患者和３０例健康人血清脂质过氧化物（ＬＰＯ）及全血超氧化物歧化酶（ＳＯＤ）的含量。结果：ＰＮＳ组和ＡＧＮ组血清ＬＰＯ均显著高于对照组（Ｐ＜０．０１）：ＰＮＳ组和ＡＧＮ组全血ＳＯＤ均显著低于对照组（Ｐ＜０．０５）。表明ＰＮＳ和ＡＧＮ患者脂质过氧化作用增强，抗氧化机能下降，提示ＰＮＳ和ＡＧＮ的发生与脂质过氧化和抗氧化失衡有关。     

脂质过氧化与抗氧化在肾小球疾病中的研究

本研究测定了２５例原发性肾病综合症（ＰＮＳ），１５例急性肾小球肾炎（ＡＧＮ）患者和３０例健康人血清脂质过氧化物（ＬＰＯ）、全血超氧化物歧化酶（ＳＯＤ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）的含量。结果：ＰＮＳ组和ＡＧＮ组血清ＬＰＯ均显著高于对照组（Ｐ＜０．０１）；ＰＮＳ组和ＡＧＮ组全血ＳＯＤ均显著低于对照组（Ｐ＜０．０５）；ＰＮＳ组和ＡＧＮ组全血（ＧＳＨ－Ｐｘ）与对照组相比，均无显著性差异（Ｐ＞０．０５）。表明ＰＮＳ和ＡＧＮ患者脂质过氧化作用增强，抗氧化机能下降，提示ＰＮＳ和ＡＧＮ的发生与脂质过氧化和抗氧化机能失衡有关。     

脱氧雪腐镰刀菌烯醇,黄曲霉毒素G1对体外培养人外周血淋巴细胞凋？…

以细胞培养、流式细胞义ＤＮＡ含量分析及ＤＮＡ琼脂糖凝胶电泳方法研究了我国食管癌高发区磁县居民粮食中优势污染霉菌毒素脱氧雪腐镰刀菌烯醇（ＤＯＮ）和黄曲霉毒素Ｇ１（ＡＦＧ１）对人淋巴细胞凋亡的影响,流式细胞术（ＦＣＭ）检测结果显示,ＤＯＮ、ＡＦＧ１处理组淋巴细胞出现了典型的亚二倍体凋亡细胞峰,凋亡百分率与毒素作用时间（ＤＯＮ,２－７２小时;ＡＦＧ１;２－２４小时）及测量（ＤＯＮ;５０－２０００μｇ／Ｌ     

一氧化氮在急性肝衰竭中的作用

为探讨ＮＯ在急性肝衰竭中的作用，采用Ｄ－ＧａｌＮ（８００ｍｇ／ｋｇ）和ＬＰＳ（８μｇ／鼠）腹腔注射复制大鼠急性肝衰竭模型，用氨胍（ＡＧ，１００ｍｇ·ｋｇ－１·ｄ－１）和左旋精氨酸（ＬＡ，４００ｍｇ·ｋｇ－１·ｄ－１）皮下注射３ｄ，分别抑制和促进ＮＯ的合成，注射Ｄ－ＧａｌＮ和ＬＰＳ后２４ｈ处死，留血清测定ＮＯ、ＡＬＴ和ＡＳＴ的水平，肝组织测定诱导型ＮＯ合酶（ｉＮＯＳ）的活性并作组织学观察。结果发现急性肝衰竭时ＮＯ和ｉＮＯＳ的水平升高（Ｐ＜００５），与ＡＬＴ和ＡＳＴ的升高相一致（Ｐ＜００５），抑制ｉＮＯＳ的活性或促进ＮＯ的合成，则ＮＯ、ＡＬＴ和ＡＳＴ的水平降低（Ｐ＜００５）或升高（Ｐ＜００５），组织学观察证实了上述结果。说明ＮＯ及ｉＮＯＳ参与急性肝衰竭，抑制ＮＯ的合成对急性肝衰竭有保护作用。     

高血压伴肥胖和高血压非肥胖患者胰岛β细胞早期分泌相的改变

为了解高血压伴肥胖者（ＯＨＴ）和高血压非肥胖者（ＮＯＨＴ）胰岛β细胞早期分泌相的变化规律，用左旋精氨酸（Ｌ－ＡＲＧ）刺激法，对ＨＴ患者胰岛β细胞分泌功能进行了研究。结果：（１）空腹胰岛素（ＩＮＳ）、Ｃ－肽（Ｃ－Ｐ）值ＯＨＴ组明显高于对照组和ＮＯＨＴ组（Ｐ＜０．０５或Ｐ＜０．０１），后两者间无明显差异（Ｐ＞０．０５）。（２）Ｌ－ＡＲＧ兴奋后ＯＨＴ和ＮＯＨＴ组ＩＮＳ和Ｃ－Ｐ分泌在４分钟时达峰值，而对照组２分钟达峰值。（３）Ｌ－ＡＲＧ兴奋后ＩＮＳ和Ｃ－Ｐ各时点增加值的和（△∑）以ＯＨＴ组明显高于对照组和ＮＯＨＴ组，后两者无显著差异。（４）ＯＨＴ组△∑ＩＮＳ与ＤＢＰ和体重指数（ＢＭＩ）均呈明显正相关（Ｐ＜０．０５），而ＮＯＨＴ组多元回归分析未发现△∑ＩＮＳ与ＤＢＰ和ＢＭＩ有相关性。结果提示ＯＨＴ患者存在胰岛素抵抗（ＩＲ），Ｌ－ＡＲＧ刺激胰岛β细胞早期分泌相是增加的；ＮＯＨＴ患者ＩＲ不明显。ＩＲ是ＯＨＴ发病的原因之一。     

空气悬浮颗粒物中硝基多环芳烃化合物粒径分布的研究

作者利用１２段安德森采样器（＜０．１３～１２．ｌμ）和高效液相色谱法对室内外２－硝基芴（２－ＮＦ）、３－硝基荧蒽（３－ＮＦｌｒ）、１－硝基芘（１－ＮＰ）、６－硝基（６．ＮＣ）和６－硝基苯并（ａ）芘（６－ＮＢａＰ）在悬浮粒子中的粒径分布进行了研究。结果表明，空气颗粒物中的ＮＯ２－ＰＡＨ．７５．７％（室外）至８７．７％（室内）存在于粒径小于２．５μｍ的粒子中，室外空气颗粒物中５种ＮＯ２－ＰＡＨ的浓度均高于室内（Ｉ／Ｏ均值为０．６９），但室内空气颗粒上ＮＯ２－ＰＡＨ．的质量浓度高于室外。室内外样本中ＮＯ２－ＰＡＨ．、ＰＡＨ．和颗粒物浓度相互间以及各项目室内外浓度间几乎均有显著或高度显著性相关。     

PON1 and Mediterranean Diet

The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases. Paraoxonase 1 (PON1) has been implicated in the development of those conditions, especially atherosclerosis. The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme. Despite the differential response of some genetic polymorphisms, the Mediterranean diet has been shown to exert a protective action on this enzyme. Extra virgin olive oil, the main source of fat, has been particularly effective in increasing PON1 activity, an action that could be due to low saturated fatty acid intake, oleic acid enrichment of phospholipids present in high-density lipoproteins that favor the activity, and increasing hepatic PON1 mRNA and protein expressions induced by minor components present in this oil. Other Mediterranean diet constituents, such as nuts, fruits and vegetables, have been effective in modulating the activity of the enzyme, pomegranate and its compounds being the best characterized items. Ongoing research on compounds isolated from all these natural products, mainly phenolic compounds and carotenoids, indicates that some of them are particularly effective, and this may enhance the use of nutraceuticals and functional foods capable of potentiating PON1 activity.     

Developmental Changes in PON1 Enzyme Activity in Young Children and Effects of PON1 Polymorphisms

Background

Paraoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorus pesticides (OPs) and is also involved in oxidative stress pathways.

Objectives

PON1 activity in newborns is lower than in adults, but the ontogeny of PON1 activity is poorly characterized in young children. We examined the effects of age and PON1 genotype on enzyme activity in a birth cohort of Mexican-American children.

Methods

We determined three substrate-specific measures of PON1 activity in 1,143 plasma samples collected longitudinally from 458 children at five time points from birth through 7 years of age, and genotyped PON1 polymorphisms at positions 192 and –108 in these children.

Results

Contrary to previous reports that PON1 activities plateau by 2 years of age, we observed an age-dependent increase in all three PON1 measures from birth through 7 years of age (p < 0.0001). The PON1₁₉₂ genotype significantly modified the effect of age on paraoxonase (POase) activity (p < 0.0001) such that increases in enzyme activity with age were influenced by the number of R alleles in a dose-dependent manner. Children with the PON1_-108CC192RR diplotype had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with children with the PON1_-108TT192QQ diplotype.

Conclusions

Lower levels of the PON1 enzyme, which is involved in protection against OPs and oxidative stress, persist in young children past 2 years of age through at least 7 years of age. Future policies addressing pesticide exposure in children should take into account that the window of vulnerability to OPs in young children may last beyond infancy.     

Interethnic variability of plasma paraoxonase (PON1) activity towards organophosphates and PON1 polymorphisms among Asian populations--a short review

Organophosphate (OP) poisoning is a progressively worrying phenomenon as worldwide pesticide production and consumption has doubled. On average, WHO estimates that 3% of agricultural workers in developing Asian countries suffer an episode of pesticide poisoning every year. Furthermore, the threat of OP usage in terrorism is existent, as seen by the subway tragedy in Tokyo in 1995 where sarin was used. Despite these alarming facts, there is currently no global system to track poisonings related to pesticide use. Human serum paraoxonase (PON1) is the enzyme that hydrolyses OP compounds. Serum PON1 levels and activity vary widely among different ethnic populations. Two commonly studied polymorphisms of PON1 are PON1Q192R and PON1L55M. PON1R192 hydrolyses paraoxon faster than PON1Q192 but hydrolyses diazoxon, sarin and soman eight times slower, and vice versa. PON1M55 has lower plasma levels of PON1 than PON1L55. As the prevalence of the different alleles and genotypic distribution vary between the Asian populations we studied, we propose the necessity to study PON1 polymorphisms and its role in OP toxicity in Asian populations. This would help safeguard the proper care of agricultural workers who might be affected by OP poisoning, and alert relevant anti biological terrorism agencies on possible risks involved in the event of an OP attack and provide effective counter measures.     

Increased influence of genetic variation on PON1 activity in neonates

PON1 (paraoxonase-1) detoxifies organophosphates by cleavage of active oxons before they have a chance to inhibit cholinesterases. The corresponding gene PON1 has common polymorphisms in both the promoter (-909, -162, -108) and the coding region (L55M, Q192R). The five PON1 genotypes were determined for maternal blood (n= 402) and cord blood (n= 229) as part of a study of the effects of organophosphate pesticide exposure on infant growth and neurodevelopment. PON1 enzymatic activities were determined for a majority of subjects. The population contained Caucasians, Caribbean Hispanics, and African Americans. PON1 activity was strongly dependent upon the promoter alleles in both maternal and cord blood. For example, PON1 activities for position -108CC, CT, and TT mothers were 146, 128, and 109 arylesterase U/mL (analysis of variance, p< 0.0001), whereas the same PON1 activities for the respective cord bloods were 49.0, 32.4, and 23.2 U/mL (p < 0.0001). Compared with adults, neonates had lower PON1 activity, implying reduced capacity to detoxify organophosphates. In addition there was a larger difference in activity between genotype groups in neonates than in adults. Because the five polymorphisms in PON1 occur in a short stretch of DNA, they were tested for linkage disequilibrium (LD). Significant LD was found among all three promoter polymorphisms as well as between promoter polymorphisms and L55M, with the strongest LD for Caucasians and the weakest for African Americans. The Caribbean Hispanics fall between these two groups. Surprisingly, significant LD also was observed between the promoter polymorphisms and C311S in PON2. LD between the promoter polymorphisms and Q192R was not significant.     

Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR

BACKGROUND: Impaired metabolism of toxic chemicals is a postulated mechanism underlying multiple chemical sensitivity (MCS). Because genetic variation alters the rate of chemical metabolism, this study was designed to determine if MCS cases differed from controls for genetic polymorphisms in drug-metabolizing enzymes. METHODS: Female Caucasian participants (203 cases and 162 controls) were drawn from a larger case-control study based on a reproducible and validated case definition. Common polymorphisms for CYP2D6, NAT1, NAT2, PON1, and PON2 were genotyped. RESULTS: Comparing cases and controls, significant differences were found in genotype distributions for CYP2D6 (P = 0.02) and NAT2 (P = 0.03). Compared with the referent homozygous inactive (CYP2D6) or slow (NAT2) metabolizers, the odds for being CYP2D6 homozygous active (OR = 3.36, P = 0.01) and NAT2 rapid (OR = 4.14, P = 0.01) were significantly higher in cases than controls. The odds for being heterozygous for PON1-55 (OR = 2.05, P = 0.04) and PON1-192 (OR = 1.57, P = 0.04) were also significantly higher in cases. CONCLUSIONS: A genetic predisposition for MCS may involve altered biotransformation of environmental chemicals. The CYP2D6 enzyme activates and inactivates toxins; the NAT2 enzyme bioactivates arylamines to protein-binding metabolites. A gene-gene interaction between CYP2D6 and NAT2 suggested that rapid metabolism for both enzymes may confer substantially elevated risk (OR = 18.7, P = 0.002). Our finding parallels others' observation of a link between PON1 heterozygosity and neurological symptoms in Gulf War syndrome. This first demonstration of genetic variation in drug-metabolizing enzymes in association with MCS requires replication. However, it suggests new research directions on genetically variable toxin pathways that might be important in MCS.     

Arylesterase activity and antioxidant status depend on PON1-Q192R and PON1-L55M polymorphisms in subjects with increased risk of cardiovascular disease consuming walnut-enriched meat

Human paraoxonase (PON1) exists in 2 major polymorphic forms and has been shown to protect LDL and HDL against oxidation. The aim of this study was to assess the differences between subjects at increased risk of cardiovascular disease (CVD), taking into account the effects of PON1-Q192R and PON1-L55M polymorphisms on 1) basal serum arylesterase activity, lipid peroxidation (LPO), and LDL-cholesterol (LDL-C), HDL-C, total cholesterol (TC), and oxidized-LDL (ox-LDL) concentrations; 2) the relations between arylesterase activity and lipid variables; and 3) the effect of walnut-enriched meat (WM) consumption on arylesterase activity and lipid variables. Twenty-three Caucasians at increased risk of CVD were randomly assigned to diet order groups in a crossover, nonblinded, placebo-controlled trial, consisting of two 5-wk experimental periods [WM and control meat (CM)]. Significant PON1-L55M x PON1-Q192R interactions affected basal serum HDL-C (P = 0.019), LDL-C (P = 0.028) and TC (P = 0.022) and tended to affect arylesterase activity (P = 0.083). Basal arylesterase activity was positively correlated with basal HDL-C (r = 0.53; P < 0.05) and TC (r = 0.43; P < 0.05) and negatively correlated with LPO (r = -0.70; P < 0.01) and the ox-LDL:LDL ratio (r = -0.63; P < 0.01). WM decreased arylesterase activity in PON1-55M carriers (P = 0.012) but not in PON1-L55 individuals, and decreased LPO concentrations in PON1-192R carriers (P = 0.031) but not in PON1-Q192 subjects. To conclude, serum TC, HDL-C, and LDL-C concentrations and arylesterase activity depend on the interaction of PON1-L55M and PON1-Q192R polymorphisms. However, the PON1-Q192R polymorphism is more closely related to antioxidant status. Both polymorphisms modulate the effect of WM consumption on CVD biomarkers.     

汉族人芳香二烷基磷酸酯酶启动子-162A／G基因多态性与冠心病发病的关系

目的　研究湖北地区汉族人芳香二烷基磷酸酯酶 (paraoxonasc ,PON1)启动子基因 -162位Ala -Gly基因多态性与冠心病 (CHD)发病的关系。方法　应用多聚酶链反应 -限制性片段长度多态性的分析方法 (PCR -RELP)检测湖北汉族地区CHD患者及正常对照组PON1基因启动子 -162位点的多态性 ,血脂用酶法测定。结果　PON1启动子 -162位点存在多态性 ,有AA ,AG ,GG 3种基因型。 12 8例正常人中AA基因型占 4 7% ,AG基因型占 2 0 3 % ,GG基因型占 75 0 % ,而CHD组与对照组 -162Ala-Gly 基因型分布总体构成比差异无显著性。对照组和CHD组PON基因G等位基因频率分别为 0 85 2和0 913 ,差异也无显著性 (P >0 0 5 )。结论　未发现PON1启动子基因 -162位Ala-Gly多态性与中国人CHD有关。     

PON1基因miRNA结合区SNPs与职业性铅中毒的关系

目的通过人群研究和SNP功能分析,探讨对氧磷酶1(PON1)基因3'UTR区SNPs对miRNA结合的影响,为铅中毒对心血管系统产生危害的机制提供新的思路。方法 ELISA方法检测铅中毒组和对照组中血清PON1含量,分析其在不同血铅浓度人群中的变化情况;Taqman MGB探针检测PON1基因rs854550和rs854552基因型分布情况;荧光素酶双报告基因法检测has-miR-218与rs854552所在区域结合情况。结果低浓度血铅值的个体PON1血清水平显著下降(P0.05);rs854550和rs854552多态性位点在铅中毒组和对照组中未发现显著差异;报告基因实验也未能发现has-miR-218可能受rs854552影响其与3'UTR结合。结论铅暴露能引起人体PON1表达改变,但本研究尚不能证明PON1基因3'UTR区多态性在铅中毒所致心血管疾病中的作用,需进一步实验寻找相关易感SNP,为明确铅中毒分子机制提供依据。