青石棉染尘大鼠血,肺中SOD,LPO变化的研究

对大鼠经气管内注入青石棉纤维，在染尘后９０、１８０、２７０、３６０和５４０天动态观察血和肺中超氧化物歧化酶（ＳＯＤ）、脂质过氧化物（ＬＰＯ）及ＳＯＤ／ＬＰＯ比值的变化。结果表明，青石棉可诱发大鼠血和肺组织中自由基反应增强，ＳＯＤ活性降低，脂质过氧化反应增高，ＬＰＯ含量升高，抗氧化能力降低，ＳＯＤ／ＬＰＯ比值降低，体内抗氧化和脂质过氧化平衡失调。     

青石棉与苯并（a）芘联合气管内染尘大鼠肺SOD的研究

青石棉与苯并（ａ）芘联合气管内染尘大鼠肺ＳＯＤ的研究杨青罗素琼刘学泽詹承烈作者对大鼠气管内注入青石棉与苯并（ａ）芘，动态观察肺组织超氧化物歧化酶（ＳＯＤ）活性变化，报告如下。一、材料与方法１．实验用粉尘：选用云南某地青石棉，经本室研制成染尘用纤维粉尘...     

青石棉、苯并(a)芘气管染尘大鼠血中SOD和LPO变化的研究

为了观察青石棉、苯并（ａ）芘染尘大鼠血中超氧化物歧化酶（ＳＯＤ）和脂质过氧化物（ＬＰＯ）的变化，以探讨其致癌机制，用气管内染尘法，在染尘后９０，１８０，２７０，３６０和５４０天时观察大鼠ＳＯＤ、ＬＰＯ及ＳＯＤ／ＬＰＯ比值的变化，采用方差分析处理数据。结果提示，青石棉、苯并（ａ）芘可致ＳＯＤ活性降低、ＬＰＯ含量升高、ＳＯＤ／ＬＰＯ比值降低的趋势。表明体内抗氧化和脂嵵使趸胶馐У鳌     

青石棉与苯并（a）芘联合诱发大鼠肺癌Ki—ras癌基因点突变

用青石棉＋苯并（ａ）芘磺油混悬液对大鼠气管注入染尘，取染尘后１８０和２７０天剖检的肺组织标本２５例。提取标本中ＤＮＡ，用人工合成的寡核酸引物进行ＰＣＲ体外扩增，再用ｒ－＾３２ＰＡＴＰ标记正常和两种突变Ｋｉ－ｒａｓ１２位探，杂交，放射自显影响。     

青石棉与苯并（a）芘联合诱发大鼠肺癌Ki－ras癌基因点突变

用青石棉＋苯并（ａ）芘碘油混悬液对大鼠气管注入染尘，取染尘后１８０和２７０天剖检的肺组织标本２５例。提取标本中ＤＮＡ，用人工合成的寡核苷酸引物进行ＰＣＲ体外扩增，再用γ－３２ＰＡＴＰ标记正常和两种突变Ｋｉ－ｒａｓ１２位探针，杂交，放射自显影。结果表明，正常对照组７例标本Ｋｉ－ｒａｓ１２位点突变为阴性，青石棉＋苯并（ａ）芘组１８例标本中，３例Ｋｉ－ｒａｓ１２位点突变为阳性，其中２例由ＧＧＴ（Ｇｌｙ）突变为ＡＧＴ（Ｓｅｒ），１例由ＧＧＴ（Ｇｌｙ）突变为ＴＧＴ（Ｃｙｓ），并对突变原因进行了探讨。     

100例矽肺患者血清中NO、LPO、SOD的观察

测定某企业100名尘肺患者和105名健康工人血清中NO、LPO的含量及SOD的活力。矽肺患者血清中NO和LPO含量高于对照组(P<0.05),SOD活力低于对照组(P<0.05),矽肺患者血清中NO含量与SOD的活性之间呈负相关关系(P<0.05),而NO含量与LPO及LPO与SOD之间无相关关系(P>0.05)。对照组人群血清中3项指标之间均无相关关系(P>0.05)。提示尘肺患者体内氧自由基反应异常,氧化/抗氧化状态严重失衡。 更多还原     

青石棉胸腔染尘大鼠血过氧化脂质和超氧化物歧化酶的变化

四川盐源县青石棉进行大鼠胸膜腔染尘后分别于12,15,18个月测定了血浆过氧化脂质(LPO)和超氧化物歧化酶(SOD)含量。LPO值随染尘时间延长逐渐上升,分别为3.078,3.918和5.565μg/ml血浆,与对照组比较差异有显著性(P<0.05)。SOD含量变化不显著,从而提出SOD/LPO比值评价体内氧化和抗氧化能力的关系。实验组较对照组比值下降明显,提示大鼠接触青石棉后脂质过氧化作用加强,机体抗氧化能力减弱,这可能是石棉致病的原因。     

不同孕期孕妇血与脐带血LPO、SOD、VE和总胆固醇水平的观察

本文用完全随机设计，观察了91例正常孕妇不同孕期和血37例新生儿脐血的LPO、SOD、VE和总胆固醇水平，并以27例正常非孕妇作对照分析。结果表明：不同孕期孕妇血中的LPO、SOD、VE及总胆固醇水平都显著高于非孕妇，并随妊娠进展呈进行性上升；新生儿脐血的该四项指标均显著低于母血；非孕妇和脐血的LPO、SOD水平接近，而脐血的VE和总胆固醇水平显著低于非孕妇。该结果对妊娠及分娩后的母婴营养保健工作具有指导意义。     

Enhanced Bio-Mineralization by Riboflavin Photosensitization and its Significance to Detoxification of Benzo[a]pyrene

In this study, ¹⁴C-benzo[a]pyrene (BaP) was chosen as a model compound to investigate if photosensitization by riboflavin enhances the subsequent microbial mineralization of polycyclic aromatic hydrocarbons (PAHs) in natural aquatic environments. After photolysis, BaP showed an increased toxicity to human epithelial cell and natural microbial assemblage. However, BaP mineralization rate in a river water sample containing riboflavin is roughly twice of that without riboflavin after the 2-day incubation. Thus, the results imply that microbial assemblage can mineralize BaP photoproducts to carbon dioxide and a combination of riboflavin photosensitization and microbial degradation could lead to complete detoxification of PAHs.     

Flavonoids Protect Against Intercellular Adhesion Molecule-1 Induction by Benzo[a]pyrene

Dietary changes are an attractive means of protecting against environmental chemical exposure. Exposure to benzo[a]pyrene (B[a]P) is a risk factor for cardiovascular disease events. It has recently been shown that B[a]P can increase intercellular adhesion molecule-1 (ICAM-1) in endothelial cells, a possible means of promoting cardiovascular disease. This study investigated the ability of flavonoids to protect against B[a]P-induced ICAM-1. It was shown that only flavonoids that contain a 4′ B-ring hydroxyl substitution and a 2–3 C-ring double bond were protective. These data suggest that selected bioactive compounds can decrease proinflammatory properties of environmental chemicals such as B[a]P.     

煤尘及其苯并[a]芘混合物细胞遗传毒性研究

目的探讨煤尘及其苯并[a]芘混合物有无细胞遗传毒性。方法分别用烟煤、无烟煤、褐煤粉尘及其与苯并[a]芘混合物的二甲基亚砜混悬液,作人外周血淋巴细胞姐妹染色单体交换(SCE)试验。试验分为加与不加体外代谢活化系统(S9)2部分。将三种煤尘及其苯并[a]芘混合物各分为500μg/皿、50μg/皿和5μg/皿3个剂量组并各设三个平行样;设生理盐水(NS)为阴性对照;二甲基亚砜(DMSO)为溶剂对照;丝裂霉素C和环磷酰胺为阳性对照。全部标本37℃培养72 h后制成染色体标本玻片,油镜下观察、计数细胞第二增殖周期分裂相的染色单体交换频率。结果3种煤尘在加和不加S9时均不能使SCE频率升高。苯并[a]芘在不加S9时无诱变作用,加入S9后可使SCE频率显著高于DMSO组(P<0.05)。丝裂霉素C和环磷酰胺均使SCE频率显著升高(P<0.05)。三种煤尘与苯并[a]芘的混合物加入S9后,其SCE频率显著高于DMSO组(P<0.05),但与加入S9的苯并[a]芘组相比,差异无统计学意义(P>0.05)。结论三种煤尘及其苯并[a]芘混合物均未见细胞遗传毒性作用。     

苯并[a]芘、铅染毒小鼠神经毒性及脑组织细胞凋亡的研究

目的研究苯并[a]芘(BaP)、铅及其联合作用引起的小鼠神经毒性及脑组织细胞凋亡.方法将80只昆明小鼠随机分为10组,即:①未处理对照组;②溶剂(植物油)对照组;③低浓度铅(5.4 mg/L,饮水)染毒组;④高浓度铅(54 mg/L,饮水)染毒组;⑤低剂量BaP(0.5 mg/kg体重,每周4次腹腔注射)染毒组;⑥高剂量BaP(5 mg/kg体重,每周4次腹腔注射)染毒组;⑦低浓度铅 低剂量BaP联合染毒组;⑧低浓度铅 高剂量BaP联合染毒组;⑨高浓度铅 低剂量BaP联合染毒组;⑩高浓度铅 高剂量BaP联合染毒组.实验中观察记录一般情况,处理8周后测脑脏器系数,TUNEL法检测小鼠脑组织细胞凋亡率并对凋亡率与脑脏器系数进行相关分析.结果①高浓度BaP单独染毒组(0.98%)及各联合染毒组(0.95%、0.93%、0.92%、0.90%)小鼠脑组织脏器系数低于对照组(1.08%、1.08%, P＜0.05～P＜0.000 1).②除低剂量铅单独染毒组外的其余各染毒组小鼠脑组织细胞凋亡率(11.91%、18.09%、44.62%、20.12%、60.84%、52.28%、90.17%)显著高于对照组(5.89%、5.87%, P＜0.000 1). ③细胞凋亡率与小鼠脑组织脏器系数间存在负相关关系(r=-0.827 1,P＜0.05).结论①BaP、铅对小鼠均有一定的中枢毒性,两者联合作用可使毒性增强;②细胞凋亡可能是BaP引起中枢神经系统毒性的机制之一.     

苯并(a)芘作用下的人支气管上皮细胞DNA损伤与XPF、XPG和ERCC1蛋白表达的关系

目的探讨苯并(a)芘(Benzo[a]pyrene,B[a]P)作用下人支气管上皮细胞(16HBE)DNA损伤与着色性干皮病F、G蛋白[Xeroderma pigmentosum group F,G(XPF,XPG)]和切除修复交叉互补蛋白1(Excision repair cross-complementing 1,ERCC1)表达的关系。方法用B[a]P(0,1,2,4,8,16,32,64μmol/L)染毒16HBE细胞24h,用噻唑蓝(Methylthiazoletetrazolium,MTT)法检测B[a]P对细胞的毒作用。用Comet实验检测细胞DNA损伤并以Olive尾矩值(Olive Tail Moments,OTM)评价DNA损伤程度。用Western-blot检测XPF、XPG和ERCC1蛋白的表达水平。结果B[a]P浓度大于4μmol/L的各组细胞活性均显著性降低(P<0.05)。各染毒组细胞DNA损伤程度则明显增高(P<0.05)。在不同浓度B[a]P染毒细胞中目的蛋白的表达量有差异。在1μmol/L和2μmol/L B[a]P组细胞XPF、XPG表达增高,且2μmol/L组XPG水平与对照组相比,差异有统计学意义(P<0.05),但随染毒剂量增大(32,64μmol/L),XPF和XPG表达量明显降低(P<0.05)。ERCC1表达随染毒剂量的增高而逐渐增加,在16μmol/L达到峰值,随后逐步下降。回归分析显示XPF、XPG和ERCC1的表达与OTM值之间决定系数分别为0.691、0.745和0.642。结论B[a]P引起的XPF、XPG和ERCC1蛋白表达水平的变化与DNA损伤之间存在密切关系。     

磷酸化Rb在苯并[a]芘致皮质神经元凋亡中的作用

目的探讨磷酸化视网膜母细胞瘤蛋白（phospho-retinoblastoma protein,p-Rb）在苯并[a]芘致神经元凋亡过程中的作用。方法用CCK-8试剂检测细胞活性;Annexin—V／PI双染法检测细胞凋亡率,免疫荧光细胞化学染色观察p．Rb表达,免疫印记法（Western-blot）检测p—Rb的表达情况。结果与对照组相比,各染毒组神经元活性降低（P〈0．05）,凋亡率增高（P〈0．05）,p-Rb表达量增高（P〈0．05）,2μmol／L组加入抑制剂后细胞活性增强（P〈0．05）,凋亡率下降（P〈0．05）,p—Rb阳性细胞数减少（P〈0．05）,p-Rb表达量降低（P〈0．05）。结论苯并[a]芘可引起磷酸化Rb水平升高,是苯并[a]芘致神经元凋亡的可能机制。     

苯并[a]芘亚慢性染毒对大鼠海马胆碱能系统的影响

目的 通过观察亚慢性染毒苯并[a]芘(B[a]P)对大鼠神经行为及海马组织中乙酰胆碱(Ach)含量、胆碱酯酶(AChE)活力和乙酰胆碱受体α7亚型(nAChRα7)mRNA和蛋白表达的影响,探讨B[a]P的神经毒性机制.方法 选择60只健康雄性SD大鼠,随机分为空白对照组,溶剂对照组,1.0、2.5、6.25 mg/kg B[a]P染毒组,隔日腹腔注射连续染毒90 d.Morris水迷宫和跳台试验检测大鼠学习记忆能力.碱性羟胺法检测海马组织Ach含量,DNTB法检测AChE活力.荧光定量PCR和Western-blot法分别检测海马组织nAChRα7 mRNA和蛋白表达水平.结果 Morris水迷宫、跳台试验结果显示,2.5、6.25 mg/kg B[a]P组大鼠学习记忆能力比空白和溶剂对照组大鼠明显下降,差异有统计学意义(P＜0.05).2.5、6.25 mg/kgB[a]P组大鼠海马组织Ach含量明显低于空白、溶剂对照和1.0 mg/kg B[a]P组,差异有统计学意义(P＜0.05),6.25 mg/kg B[a]P组AChE活力明显低于空白对照、溶剂对照和1.0 mg/kg B[a]P组,差异有统计学意义(P＜0.05).各组之间nAChRα7 mRNA和蛋白表达水平的差异无统计学意义(P＞0.05).大鼠海马组织Ach含量与大鼠平均逃避潜伏期和总路程呈负相关(相关系数r分别为-0.567和-0.503,P＜0.01),与平台象限滞留时间呈正相关(r=0.800,P＜0.01).结论 亚慢性染毒B[a]P可损伤大鼠学习记忆功能,其机制与大鼠海马组织Ach含量下降有关     

孕期暴露苯并[a]芘对子代大鼠神经发育毒性的影响

Objective To study the effects of prenatal exposure to benzo[a]pyrene (B[a]P) on the physical development, early behavioral development, the adaptability to new environment and the learning and memory ability of rat offspring. Methods Pregnant rats were randomly divided into five groups: control group,olive oil group, 3 exposure groups (25, 50 and 100 mg/kg B [a]P). The rats were exposed to B [a]P) by intraperitoneal injection on the 17th-19th days during gestation. The offspring were weighed on postnatal days (PND)1, PND 4, PND 7 and PND 28, the indices of physical development, reflective ability and sensory function were detected for offspring, the Morris water maze and Open-field tests were used to measure the ability of learning and memory and the adaptability to new environment of offspring. Results The time of ear opening in middle and high-dose groups[(4. 1 ±0.4),(5.0±0.4) d] was posterior to that in untreated and solvent groups[(3.3±0.5),(3.4±0.6) d](P＜0.01).The attainment rate (6.5%) of the surface righting reflex test in highdose group on the 4th day was significantly lower than that (36.1%) in untreated group, the attainment rate(50.0%) in high-dose group on PND7 was significantly lower than those (81.3% and 79.3%) in untreated group and solvent group (P＜0.05). Compared to the untreated group, the time of forelimb hanging test in all exposure groups on PND12 and PND14 significantly decreased; compared to the solvent group the time of forelimb hanging test decreased in high-dose group on the 14th day significantly decreased (P＜0.01). The attainment rate (61.9%) of olfactory discrimination in high-dose group on PND 12 was significantly lower than that (94.3%) in untreated group (P＜0.05). The results of morris water maze test showed that the escape latency of different dose groups significantly increased, and the time of spatial probe and the times of traversing flat in high-dose group decreased significantly, as compared to the untreated and solvent groups(P＜0.01). The results of open-field test indicated that the center retention time in middle and high-dose groups significantly prolonged, the times of crossing lattice obviously reduced, and the rearing times decreased in high-dose group,as compared to untreated(P＜0.05).Compared to the solvent group, the times of crossing lattice in all exposure groups reduced significantly(P＜0.01 or P＜0.05). Conclusion The prenatal exposure to B[a]P could inhibit the physical development and early behavioral development, and influence the adaptability to new environment and learning and memory ability for offspring.