烟气暴露30天对大鼠心脏基因表达谱的影响

目的：利用基因芯片技术研究烟气暴露30 d对大鼠心脏基因表达的影响。方法：6只雄性SD大鼠分为对照组和烟气暴露组。烟气暴露组经主流烟气暴露,对照组不进行干预,30 d后取大鼠心脏,应用基因芯片技术进行差异表达基因筛选,利用基因本体（GO）和京都基因与基因组百科全书（KEGG）数据库对差异基因进行生物信息学分析。结果：与对照组比较,烟气暴露组筛选出差异表达2倍以上的基因86个,其中上调表达60个,下调表达26个。差异表达基因富集于292种生物过程,72种细胞成分和96类分子功能以及61个信号通路。主要涉及促分裂原活化蛋白激酶结合、α-βT细胞受体复合物、细胞外渗的正调节、络氨酸代谢等相关基因通路。结论：烟气暴露30 d所致大鼠心脏的异常表达基因与信号通路主要涉及分子结合、细胞周期、信号转导等多个方面。     

邻苯二甲酸二辛酯亚慢性暴露对SD大鼠血细胞的影响

目的：探讨邻苯二甲酸二辛酯（DEHP）对大鼠血细胞的影响。方法：SD大鼠设对照组（饲喂基础饲料）、4个DEHP染毒组（分别为5、50、500和2 500 mg/kg）,每组20只,雌雄各半,连续饲喂染毒90 d。染毒结束后,取大鼠全血测定各类血细胞的变化。结果：与对照组相比,白细胞参数中,2 500 mg/kg组雄性大鼠嗜酸性粒细胞显著减少（P < 0.01）,雌性大鼠白细胞总数显著降低（P < 0.05）;500和2 500 mg/kg组雌性大鼠淋巴细胞显著增加（P < 0.05）。红细胞参数中,2 500 mg/kg组雄性大鼠红细胞总数、血红蛋白（HGB）和红细胞压积（HCT）显著下降（P < 0.01）;雌性大鼠500和2 500 mg/kg组血红蛋白（HGB）显著下降（P < 0.05）;500和2 500 mg/kg组的平均血红蛋白含量（MCH）显著下降（P < 0.05或P < 0.01）;2 500 mg/kg组的平均血红蛋白浓度（MCHC）和直接测定的血红蛋白浓度（CHCM）显著下降（P < 0.05或P < 0.01）。未发现DEHP对雌雄大鼠血小板各指标产生影响。结论：一定剂量条件下,DEHP可对大鼠白细胞和红细胞相关指标产生影响。     

阈下氯胺酮伍合异丙酚在肿瘤病人全麻诱导期对心血管系统的影响

目的：评估预注氯胺酮预防异丙酚在肿瘤病人全麻诱导插管期所致血压下降的作用。方法;２６例肿瘤择期手术全麻病人,随机分为Ｐ组和Ｋ＋Ｐ组各１３例,分别用工分太尼３μｇ／ｋｇ、异丙酚２ｍｇ／ｋｇ及氯胺酮０．８ｍｇ／ｋｇ,芬太尼３μｇ／ｋｇ,划丙酚２ｍｇ／ｋｇ,异丙酚２ｍｇ／ｋｇ行全麻诱导。比较两组病例在诱导前后及气管插管后收缩压（ＳＢＰ）、平均动脉压（ＭＡＰ）、舒张压（ＤＢＰ）和心率（ＨＲ）的变化。结果：     

硝酸铈亚慢性暴露对大鼠神经行为功能的影响

目的：评估硝酸铈[Ce(NO3)3]亚慢性(90 d)暴露对SD大鼠神经行为功能的影响,为稀土元素铈的风险评估提供科学依据。方法：选用初断乳SD大鼠,根据体质量随机分为4组,分别为正常对照组(ddH2O),Ce(NO3)3低剂量组20 mg/(kg·d)、中剂量组100 mg/(kg·d)和高剂量组500 mg/(kg·d),每组雌雄鼠各12只。灌胃染毒90 d后进行高架十字迷宫实验、旷场实验、转棒实验和Morris水迷宫实验。通过HE染色对各组大鼠脑组织进行病理学检测。结果：与对照组相比,硝酸铈经口暴露90 d后,转棒实验结果显示硝酸铈各剂量组雌、雄大鼠的在棒时间差异无统计学意义(P>0.05);旷场实验和高架十字迷宫实验结果表明进入中央区次数、中央区停留时间、进入开臂次数百分比和进入开臂时间百分比等指标的差异均无统计学意义(P>0.05);Morris水迷宫实验结果显示4 d定位航向实验的逃避潜伏期和空间探索实验的各个指标,包括进入目标象限次数、目标象限游泳时间和穿过原平台次数等差异均无统计学意义(P>0.05)。脑组织HE染色结果也未观察到明显的中毒病理特征。结...     

极低频电磁场暴露对大鼠脑电图及脑组织结构的影响

目的探讨极低频电磁场对大鼠脑电图及脑组织结构的影响。方法选用二级雄性Wistar大鼠48只,随机分为对照组和磁场暴露组,每组24只,磁场暴露组大鼠置于ELF-EMFS(50 Hz,400μT,<1V/M)中连续暴露60 d。终止暴露后6 h、7 d、15 d和30 d,采用MP150生理监测仪监测脑电图近似熵和功率谱分布;采用光镜观察大脑皮层组织结构。结果 (1)磁场组大鼠脑电图(EEG)于暴露后6 h和7 d,近似熵降低;(2)磁场组大鼠EEG信号于6 h出现δ频段相对功率值呈升高改变,而β频段相对功率值降低;对照组和入场前磁场组大鼠EEG基本节律为30μV左右的β波及少量不典型α波,偶见低幅θ波和δ波,磁场组大鼠θ波和δ波增多以及波幅增加,以β波为主要节律。(3)磁场组大鼠大脑皮层神经元呈缺血性改变。结论极低频电磁场暴露会导致大鼠EEG近似熵降低、功率谱分布异常及脑组织结构损伤,且此改变主要发生于终止暴露后早期。     

静注压宁定对气管插管心血管反应的影响

将４０例病人随机分为压中定组（ｎ＝２０），对照组（ｎ＝２０）。以０．５ｍｇ·ｋｇ－１压宁定诱导插管，观察诱导即刻、１ｍｉｎ、３ｍｉｎ和插管时，插管后１ｍｉｎ、５ｍｉｎ时两组病人的收缩压（ＳＢＰ）、舒张压（ＤＢＰ）、心率（ＨＲ）变化。结果表明：压宁定组的ＳＢＰ、ＤＢＰ在插管时低于对照组（Ｐ＜０．０５）；ＨＲ在插管前后无差异（Ｐ＞０．０５），对照组ＨＲ在插管后明显上升，差异显著（Ｐ＜０．０５）。插管后５ｍｉｎ两组ＳＢＰ、ＤＢＰ及ＨＲ无差异（Ｐ＞０．０５）。表明压宁定可以预防气管插管时的心血管反应。     

亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

目的：观察稀土化合物硝酸钇[Y（NO₃）₃]亚慢性（90 d）暴露对大鼠学习记忆能力的影响,并探究其可能的机制,为全面评估稀土元素钇的健康风险提供科学依据。方法：选用刚离乳（PND21）SD雌性大鼠,根据质量随机分为4组,分别为对照组（ddH₂O）,Y（NO₃）₃低剂量组[10 mg/（kg·d）]、中剂量组[40 mg/（kg·d）]和高剂量组[160 mg/（kg·d）],每组15只。连续灌胃受试物90 d后进行旷场实验、高架十字迷宫实验、转棒实验、Morris水迷宫实验。水迷宫检测后,每组取5只雌鼠心脏原位灌注,进行脑组织病理学检查。每组剩余10只雌鼠摘取脑组织,紫外分光光度计检测雌鼠大脑皮质和海马中谷氨酸（Glu）的含量;Western blot检测海马组织中N-甲基-D-天冬氨酸（NMDA）受体蛋白表达情况。结果：与对照组相比,硝酸钇90 d暴露后,转棒实验中160 mg/（kg·d）剂量组大鼠在棒时间、在棒圈数、掉落速度明显升高（P<0.05）。在Morris水迷宫定位航向实验第4天时,40、160 mg/（kg·d）剂量组大鼠逃避潜伏期明显降低（P<0.05）;Morris水迷宫空间探索实验中,40 mg/（kg·d）剂量组大鼠穿越平台次数、目标象限游泳时间明显增加（P<0.05）;160 mg/（kg·d）剂量组穿越平台次数、进入目标象限次数、目标象限游泳时间明显增加（P<0.05）;160 mg/（kg·d）剂量组大鼠东北、东南、西南象限的逃避潜伏期明显低于西北象限的逃避潜伏期（P<0.05）。160 mg/（kg·d）剂量组大鼠海马中Glu含量和NMDA受体NR1含量均明显低于对照组（P<0.05）。40和160 mg/（kg·d）剂量组大鼠海马中NMDA受体NR2A含量明显低于对照组（P<0.05）。结论：硝酸钇亚慢性（90 d）暴露可以引起雌性大鼠空间学习记忆能力增强;硝酸钇可能通过降低海马组织神经元细胞外Glu含量,抑制NMDA受体激活,增强雌性大鼠的空间学习记忆能力。     

胚胎早期低剂量甲基汞暴露对大鼠的行为致畸效应

目的：探讨胚胎早期汞低剂量暴露对大鼠仔代的行为致畸效应。方法：Wistar大鼠雌性80只、雄性20只以3：1交配,孕鼠随机分为4组,于妊娠6－9d用氯经甲基汞0．00mg/(kg.bw.d）、0．01mg/(kg.bw.d）、0．05mg/(kg.bw.d）、2．00mg/(kg.bw.d）灌胃染毒。进行胚胎毒性研究;记录201只卫鼠出生后早期生理发育和神经行为发育指标;10周龄的仔鼠32只进行操作行为测试;24只进行脑组织形态学检查和单胺类神经递质（去甲紧上腺素、多巴胺、5－羟色胺）测定（荧光分光度法）。结果：胚胎早期低剂量甲基汞对胎仔体重及尾长发育有抑制作用（P＜0．01）,暴露组仔鼠的体重增长、早期生理发育及神经行为发育滞后于对照组（P＜0．05或P＜0．01）;操作行为成绩均比对照组降低9P＜0．05或P＜0．01）;3个暴露组仔鼠均未观察到脑组织形态学改变,但单胺类神经递质含量均比对照组显著增高（P＜0．05或P＜0．01）。所有结果呈现出剂量－反应关系。结论：胚胎早期低剂量甲汞暴露有一定的胚胎毒性,可影响仔鼠神经系统的发育,导致行为改变。     

砷对大鼠胚胎神经系统发育和HSP70mRNA表达的影响

应用显微解剖，原位杂交组织化学，扫描电镜等技术深入研究了三氧化二砷对大鼠胚胎的发育毒性和神经毒性及ＨＳＰ７０ｍＲＮＡ表达与胚胎神经系统发育的关系。     

硒对邻苯二甲酸酯亚慢性暴露雄性大鼠肝脏的保护作用

目的：研究邻苯二甲酸酯（DEHP）亚慢性暴露对雄性大鼠肝脏的影响及硒对大鼠肝脏的保护作用。方法：将77只雄性大鼠随机分为7组,分别设置为对照组（饲喂基础饲料）、3个DEHP染毒组（染毒剂量分别为300、600和900 mg/kg）、3个硒干预组（在相应剂量的染毒组中加入1 mg/kg酵母硒）。染毒8周,染毒期末,大鼠空腹16 h后称量大鼠体质量、采血进行生化检测以及称量肝脏质量。结果：与对照组相比,600和900 mg/kg DEHP染毒组大鼠的平均体质量明显降低（P < 0.05）;900 mg/kg DEHP染毒组大鼠的体质量增量、总摄食量、总食物利用率、明显降低（P < 0.01或P < 0.05）;各DEHP染毒组、硒干预组的肝脏平均质量、肝脏系数均明显降低（P < 0.01）。600 mg/kg DEHP染毒后的硒干预组大鼠体质量增量较相应的染毒组增加（P < 0.05）。生化指标检测结果显示,与对照组相比,600、900 mg/kg DEHP染毒组,300、600 mg/kg DEHP染毒后的硒干预组大鼠ALT浓度明显升高（P < 0.05）;900 mg/kg DEHP染毒组,300、600和900 mg/kg DEHP染毒后的硒干预组大鼠AST浓度明显升高（P < 0.01）;600、900 mg/kg DEHP染毒组大鼠TP浓度明显升高（P < 0.01）;900 mg/kg DEHP染毒组,300 mg/kg DEHP染毒后的硒干预组大鼠ALB浓度明显升高（P < 0.01）;900 mg/kg DEHP染毒组大鼠GLB浓度明显升高（P < 0.01）。900 mg/kg DEHP染毒后的硒干预组大鼠ALT、AST、TP、GLB均明显低于相应的染毒组（P < 0.01或P < 0.05）。结论：DEHP的亚慢性暴露对雄性大鼠的体质量与生长产生一定的影响,可能造成肝脏肿胀,对肝脏功能产生影响;而硒的干预可能在一定程度上缓解DEHP对肝脏的毒性作用。     

DNA and protein adducts in human tissues resulting from exposure to tobacco smoke

Tobacco smoke contains a variety of genotoxic carcinogens that form adducts with DNA and protein in the tissues of smokers. Not only are these biochemical events relevant to the carcinogenic process, but the detection of adducts provides a means of monitoring exposure to tobacco smoke. Characterization of smoking-related adducts has shed light on the mechanisms of smoking-related diseases and many different types of smoking-derived DNA and protein adducts have been identified. Such approaches also reveal the potential harm of environmental tobacco smoke (ETS) to nonsmokers, infants and children. Because the majority of tobacco-smoke carcinogens are not exclusive to this source of exposure, studies comparing smokers and nonsmokers may be confounded by other environmental sources. Nevertheless, certain DNA and protein adducts have been validated as biomarkers of exposure to tobacco smoke, with continuing applications in the study of ETS exposures, cancer prevention and tobacco product legislation. Our article is a review of the literature on smoking-related adducts in human tissues published since 2002.     

Histopathological evaluation of renal vascular changes in rats exposed to passive smoking

Cigarette smoking is an important risk factor for renal damage due to its effects on small interlobular arteries. We investigated the effects of long-term passive smoking on renal vascular structures in healthy rats exposed to smoke soon after birth. Forty-two Sprague-Dawley rats (21 males and 21 females) exposed to passive smoking comprised the experimental group and 33 non-exposed rats (17 males and 16 females) comprised the control group. The number of renal vessels, as well as the level of glomerular capillary sclerosis, hyalinosis of arterioles, and myointimal hyperplasia of arteries was assessed in renal biopsy specimens. The mean number of renal vessels in male and female rats exposed to passive smoke (21.71 and 13.81, respectively) did not significantly differ from the mean number of renal vessels in male and female control rats (22.47 and 13.06, respectively) (p>0.05). Levels of glomerulosclerosis, hyalinosis, and myointimal hyperplasia also did not differ between the experimental and control groups (p>0.05). Histopathologic evidence of renal vascular damage was not found in young rats exposed to passive smoke for 4 months. A longer or higher degree of exposure to cigarette smoke components may be required before such changes manifest, and aging and primary renal disease may play a role.     

Differential effects of cigarette smoke extracts on cell proliferation in gastric and colon cells

Substantial evidence show a higher incidence of gastric cancer in smokers than nonsmokers and that cigarette smoking is highly associated with colon cancer. The present study was designed to examine the effect of cigarette smoke extracts on gastric and colon cancer cell proliferation, which is important for tumor growth. Two different cell lines were used. One was gastric cancer cell line AGS, and the other was colon cancer cell line HT-29. It was found that cigarette smoke extracts stimulated cell proliferation and c-myc expression in AGS cells. Furthermore, this proliferative action was partially blocked by the c-myc antisense. However, the extracts significantly inhibited HT-29 cell proliferation and suppressed c-myc expression. In conclusion, cigarette smoke extracts stimulated AGS cell proliferation, while inhibiting HT-29 proliferation, which were partially mediated by a c-myc-related pathway. The former action may play a contributory role in the carcinogenic action of cigarette smoking in the stomach.     

Formation and persistence of nucleotide alterations in rats exposed whole-body to environmental cigarette smoke.

The assessment of pathological effects produced by environmental tobacco smoke in humans is controversial in epidemiological studies. On the other hand, animal models are poorly sensitive to smoke carcinogenicity. We designed an experimental study assessing the tissueselective formation and persistence of DNA adducts in smoke-exposed rats. Sprague-Dawley rats were exposed for 6 h per day, 5 days per week, to environmental smoke resulting from a mixture of sidestream and mainstream smoke generated from Kentucky 2R1 reference cigarettes. The total particulate matter was in the range of 73-93 mg/m(3). DNA adducts were measured by (32)P-post-labelling in rat organs (lung, heart, liver, bladder and testis), tissues (dissected tracheal epithelium) and cells [isolated bronchoalveolar lavage (BAL) cells]. A time-related increase of (32)P-post-labelled DNA modifications was detectable by autoradiography, in the form of massive diagonal radioactive zones and individual spots. Top levels were reached after 4-5 weeks of exposure. The ratio of smoke-induced DNA adducts to the background levels detected in sham-exposed rats was 11.2 in the tracheal epithelium, 10.4 in BAL cells, 7.3 in the heart, 6.3 in the lung, 5.1 in the bladder, 1.9 in the testis and 1. 1 in the liver. Appearance of DNA adducts in the lung was also revealed by synchronous fluorescence spectrophotometry. Smoke-related oxidative damage was demonstrated by a significant enhancement of 8-hydroxy-2'-deoxyguanosine in lung DNA. In parallel, there was a time-related induction of lung microsomal arylhydrocarbon hydroxylase activity, an elevation in cytosolic glutathione S-transferase activity, and a moderate but progressive and significant depletion of reduced glutathione. After discontinuing exposure to environmental cigarette smoke for 1 week, DNA adduct levels significantly dropped in the lung, tracheal epithelium, heart and bladder. The decrease was evident but not statistically significant in BAL cells, and was negligible in the heart. The selective localization and the differential persistence of these promutagenic nucleotide modifications in rat organs, tissues and cells suggest that exposure to environmental cigarette smoke, at least under the high exposure regimens used in experimental studies, may pose a potential risk of developing mutation-related diseases.     

Inhibition by N-acetylcysteine of carcinogen-DNA adducts in the tracheal epithelium of rats exposed to cigarette smoke

The ability of the aminothiol N-acetylcysteine (NAC) to preventthe formation of carcinogen-DNA adducts in tracheal epithelialcells was investigated in Sprague-Dawley rats exposed whole-bodyto mainstream cigarette smoke for either 40 or 100 consecutivedays. ³²P-Postlabelling analyses showed the occurrence of DNAadducts (12.49 adducts/10⁸ nucleotides) after 40 days of exposure,with a trend to formation of characteristic diagonal radioactivezones. Total adduct levels were not further enhanced after 100days of exposure to smoke, although significant changes occurredin the amounts of individual adducts. NAC, given by gavage inthe 40 day study and in drinking water in the 100 day study,significantly inhibited the formation of smoke-related carcinogen-DNAadducts in the tracheal epithelium, to such an extent that adductlevels were not significantly higher than those detected insham-exposed control rats. Together with a variety of othermolecular, clastogenicity, metabolic, cytological and histopathologicalend-points investigated in rodents and with the preliminaryevidence arising from a study in humans, these results documentthe considerable efficacy of oral NAC in inhibiting smoke-relatedcarcinogen-DNA adducts.     

Differential carcinogenicity of cigarette smoke in mice exposed either transplacentally, early in life or in adulthood

Cigarette smoke (CS) plays a dominant role in the epidemiology of human cancer. However, it is difficult to reproduce its carcinogenicity in laboratory animals. Recently, we showed that CS becomes a potent carcinogen in mice when exposure starts soon after birth. In our study, we comparatively evaluated the carcinogenic response to mainstream CS in mice at different ages. Neonatal mice were exposed daily for 4 months to CS, starting within 12 hr after birth, and sacrificed at 8 months. Adult mice were exposed for the same time period (3-7 months) and sacrificed at 11 months. Other mice were exposed transplacentally or both transplacentally and early in life. A total of 351 neonatal mice and 80 adult Swiss H mice were used. With varying intensity depending on age, CS induced pulmonary emphysema, bronchial and alveolar epithelial hyperplasia, blood vessel proliferation and hemangiomas and microadenomas in lung as well as parenchymal degeneration of liver. Histopathological alterations of kidney were only observed in mice exposed to CS early in life. Lung adenomas and malignant tumors of various histopathological nature were detected in neonatally exposed mice but not in adults. Transplacental CS induced the formation of lung adenomas in the offspring 8 months after birth. Previous exposure during pregnancy attenuated CS-related alveolar epithelial hyperplasia induced after birth. In conclusion, the carcinogenic response to CS varies depending on the developmental stage. The early postnatal life and the prenatal life are particularly at risk for the later development of CS-related tumors.     

Strain-dependent differences in susceptibility to lung cancer in inbred mice exposed to mainstream cigarette smoke

It is becoming increasingly clear that genetic susceptibility is an important host factor determining the effects of exposure to a number of airborne particles and gases. Although numerous studies have identified a genetic component for spontaneous pulmonary tumor development and for chemically induced lung cancer (e.g., urethane) in mice, a systematic examination of murine inter-strain differences in response to cigarette smoke inhalation has not been conducted. We addressed this research gap by examining the strain distribution pattern of lung cancer in nine inbred strains of mice exposed to 258 mg/m³ mainstream cigarette smoke for 5 months followed by 4 months of rest. Lung tumors were enumerated on fixed lungs visualized at low magnification and on serial step sections examined microscopically. With the low magnification examination, we observed statistically significant increases in the number of lung tumors in cigarette smoke-exposed A/J and the genetically-related A/HeJ mice (p < 0.05). While fewer tumors were identified by the microscopic enumeration method, it confirmed that significant increases in lung tumors occurred only in A/J and A/HeJ mice exposed to cigarette smoke (p < 0.05). Thus, as predicted by epidemiologic studies and animal experiments using chemically induced lung cancer models, these findings suggest that genetic host factors play a significant role in the pulmonary tumorigenic response of mice to mainstream cigarette smoke.     

Inhibition of lung tumor development by berry extracts in mice exposed to cigarette smoke

Cigarette smoke (CS) and dietary factors play a major role in cancer epidemiology. At the same time, however, the diet is the richest source of anticancer agents. Berries possess a broad array of health protective properties and were found to attenuate the yield of tumors induced by individual carcinogens in the rodent digestive tract and mammary gland but failed to prevent lung tumors induced by typical CS components in mice. We exposed whole-body Swiss ICR mice to mainstream CS, starting at birth and continuing daily for 4 months. Aqueous extracts of black chokeberry and strawberry were given as the only source of drinking water, starting after weaning and continuing for 7 months, thus mimicking an intervention in current smokers. In the absence of berries, CS caused a loss of body weight, induced early cytogenetical damage in circulating erythrocytes and histopathological alterations in lung (emphysema, blood vessel proliferation, alveolar epithelial hyperplasia and adenomas), liver (parenchymal degeneration) and urinary bladder (epithelial hyperplasia). Both berry extracts inhibited the CS-related body weight loss, cytogenetical damage, liver degeneration, pulmonary emphysema and lung adenomas. Protective effects were more pronounced in female mice, which may be ascribed to modulation by berry components of the metabolism of estrogens implicated in lung carcinogenesis. Interestingly, both the carcinogen and the chemopreventive agents tested are complex mixtures that contain a multitude of components working through composite mechanisms.     

Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8 months. We employed whole exome sequencing (WES) and quantitative proteomics to investigate the molecular alterations in oral keratinocytes chronically exposed to smoke/ chewing tobacco. Exome sequencing revealed distinct mutational spectrum and copy number alterations in smoke/ chewing tobacco treated cells. We also observed differences in proteomic alterations. Proteins downstream of MAPK1 and EGFR were dysregulated in smoke and chewing tobacco exposed cells, respectively. This study can serve as a reference for fundamental damages on oral cells as a consequence of exposure to different forms of tobacco.