中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2011年
1期
45-51
,共7页
目的 探讨大气颗粒物(PM)亚急性暴露对小鼠妊娠和胚胎发育的影响.方法选择雌、雄小鼠各40只按1∶1合笼,将妊娠的雌鼠随机分为对照(A组)、小剂量PM暴露(B组)、中剂量PM暴露(C组)、大剂量PM暴露(D组)、超大剂量PM暴露(E组),每组8～11只.从妊娠0～19 d分别向A组小鼠咽后壁接种磷酸盐缓冲液,向B、C、D、E组小鼠咽后壁接种PM标准品SRM1649a混悬液(浓度分别为0.09、0.52、1.85、69.2μg/μl).于自动分娩发生时剖宫取胎,观察孕鼠体质量、妊娠天数、仔鼠宫内存活及生长情况和肝、肺组织的病理改变,计算仔鼠肺及肝脏体系数,检测仔鼠肺CYP1A1、肝CYP1A2蛋白及mRNA的表达.结果 (1)各组孕鼠均未出现自然死亡.各组孕鼠妊娠1、7 d时体质量比较,差异均无统计学意义(P＞0.05);妊娠至14、18 d时,E组孕鼠体质量[分别为(41.8±5.8)及(48.9±8.9)g]明显低于A组[分别为(45.9±1.8)及(56.2±4.9)g],差异均有统计学意义(P＜0.05).E组孕鼠妊娠天数[(19.3±1.3)d]也明显低于A组[(20.5±0.7)d],差异有统计学意义(P＜0.05);A、B、C、D组孕鼠间妊娠天数分别比较,差异均无统计学意义(P＞0.05).各组仔鼠肺体系数及肝体系数比较,E组孕鼠[(1.21±0.18)及(4.68±0.21)%]高于A、B、C及D组,且差异均有统计学意义(P＜0.05).(2)E组仔鼠的死亡率(23.0%)高于A(0.8%)、B(0.9%)、C(1.7%)及D组(3.7%),差异均有统计学意义(P＜0.05);A、B、C、D组仔鼠的死亡率依次升高,但差异无统计学意义(P＞0.05).(3)E组仔鼠肝、肺病理改变显著,肝脏特征性病理改变包括肝组织结构紊乱、肝细胞浊肿、胞质淡染;多数肝细胞胞质内出现脂肪变性,部分肝细胞固缩,胞质深染;肝组织内见炎细胞浸润和点灶状坏死.肺特征性病理改变包括肺细支气管管腔变窄、黏膜下层小血管充血;间质、肺泡水肿,肺泡间隔增厚,泡内、细支气管周中性粒细胞及淋巴细胞浸润.C、D组上述病变程度次之,A、B组正常或变化轻微.(4)E组仔鼠肺CYP1A1和肝CYP1A2蛋白表达水平(分别为1.20±0.40及2.55±0.89)高于A组(0.77±0.36及2.08±0.31),两组比较,差异有统计学意义(P＜0.05).肺CYP1A1 mRNA表达,C(0.36±0.12)、D(0.41±0.08)、E组(0.43±0.11)高于A组(0.21±0.10),D、E组高于B组(0.28±0.10),分别比较,差异均有统计学意义(P＜0.05).肝CYP1A2 mRNA表达,C(0.37±0.13)、D(0.36±0.14)、E组(0.43±0.16)高于A组(0.21±0.03),E组高于B组(0.24±0.11),分别比较,差异均有统计学意义(P＜0.05).结论 PM具有胚胎毒性作用.超大剂量PM亚急性暴露可导致小鼠的不良妊娠结局;中、高剂量PM暴露可导致癌相关基因CYP1 A1和CYP1 A2表达的上调,可能对个体的后期发育有潜在的不良效应.
目的 探討大氣顆粒物(PM)亞急性暴露對小鼠妊娠和胚胎髮育的影響.方法選擇雌、雄小鼠各40隻按1∶1閤籠,將妊娠的雌鼠隨機分為對照(A組)、小劑量PM暴露(B組)、中劑量PM暴露(C組)、大劑量PM暴露(D組)、超大劑量PM暴露(E組),每組8～11隻.從妊娠0～19 d分彆嚮A組小鼠嚥後壁接種燐痠鹽緩遲液,嚮B、C、D、E組小鼠嚥後壁接種PM標準品SRM1649a混懸液(濃度分彆為0.09、0.52、1.85、69.2μg/μl).于自動分娩髮生時剖宮取胎,觀察孕鼠體質量、妊娠天數、仔鼠宮內存活及生長情況和肝、肺組織的病理改變,計算仔鼠肺及肝髒體繫數,檢測仔鼠肺CYP1A1、肝CYP1A2蛋白及mRNA的錶達.結果 (1)各組孕鼠均未齣現自然死亡.各組孕鼠妊娠1、7 d時體質量比較,差異均無統計學意義(P＞0.05);妊娠至14、18 d時,E組孕鼠體質量[分彆為(41.8±5.8)及(48.9±8.9)g]明顯低于A組[分彆為(45.9±1.8)及(56.2±4.9)g],差異均有統計學意義(P＜0.05).E組孕鼠妊娠天數[(19.3±1.3)d]也明顯低于A組[(20.5±0.7)d],差異有統計學意義(P＜0.05);A、B、C、D組孕鼠間妊娠天數分彆比較,差異均無統計學意義(P＞0.05).各組仔鼠肺體繫數及肝體繫數比較,E組孕鼠[(1.21±0.18)及(4.68±0.21)%]高于A、B、C及D組,且差異均有統計學意義(P＜0.05).(2)E組仔鼠的死亡率(23.0%)高于A(0.8%)、B(0.9%)、C(1.7%)及D組(3.7%),差異均有統計學意義(P＜0.05);A、B、C、D組仔鼠的死亡率依次升高,但差異無統計學意義(P＞0.05).(3)E組仔鼠肝、肺病理改變顯著,肝髒特徵性病理改變包括肝組織結構紊亂、肝細胞濁腫、胞質淡染;多數肝細胞胞質內齣現脂肪變性,部分肝細胞固縮,胞質深染;肝組織內見炎細胞浸潤和點竈狀壞死.肺特徵性病理改變包括肺細支氣管管腔變窄、黏膜下層小血管充血;間質、肺泡水腫,肺泡間隔增厚,泡內、細支氣管週中性粒細胞及淋巴細胞浸潤.C、D組上述病變程度次之,A、B組正常或變化輕微.(4)E組仔鼠肺CYP1A1和肝CYP1A2蛋白錶達水平(分彆為1.20±0.40及2.55±0.89)高于A組(0.77±0.36及2.08±0.31),兩組比較,差異有統計學意義(P＜0.05).肺CYP1A1 mRNA錶達,C(0.36±0.12)、D(0.41±0.08)、E組(0.43±0.11)高于A組(0.21±0.10),D、E組高于B組(0.28±0.10),分彆比較,差異均有統計學意義(P＜0.05).肝CYP1A2 mRNA錶達,C(0.37±0.13)、D(0.36±0.14)、E組(0.43±0.16)高于A組(0.21±0.03),E組高于B組(0.24±0.11),分彆比較,差異均有統計學意義(P＜0.05).結論 PM具有胚胎毒性作用.超大劑量PM亞急性暴露可導緻小鼠的不良妊娠結跼;中、高劑量PM暴露可導緻癌相關基因CYP1 A1和CYP1 A2錶達的上調,可能對箇體的後期髮育有潛在的不良效應.
목적 탐토대기과립물(PM)아급성폭로대소서임신화배태발육적영향.방법선택자、웅소서각40지안1∶1합롱,장임신적자서수궤분위대조(A조)、소제량PM폭로(B조)、중제량PM폭로(C조)、대제량PM폭로(D조)、초대제량PM폭로(E조),매조8～11지.종임신0～19 d분별향A조소서인후벽접충린산염완충액,향B、C、D、E조소서인후벽접충PM표준품SRM1649a혼현액(농도분별위0.09、0.52、1.85、69.2μg/μl).우자동분면발생시부궁취태,관찰잉서체질량、임신천수、자서궁내존활급생장정황화간、폐조직적병리개변,계산자서폐급간장체계수,검측자서폐CYP1A1、간CYP1A2단백급mRNA적표체.결과 (1)각조잉서균미출현자연사망.각조잉서임신1、7 d시체질량비교,차이균무통계학의의(P＞0.05);임신지14、18 d시,E조잉서체질량[분별위(41.8±5.8)급(48.9±8.9)g]명현저우A조[분별위(45.9±1.8)급(56.2±4.9)g],차이균유통계학의의(P＜0.05).E조잉서임신천수[(19.3±1.3)d]야명현저우A조[(20.5±0.7)d],차이유통계학의의(P＜0.05);A、B、C、D조잉서간임신천수분별비교,차이균무통계학의의(P＞0.05).각조자서폐체계수급간체계수비교,E조잉서[(1.21±0.18)급(4.68±0.21)%]고우A、B、C급D조,차차이균유통계학의의(P＜0.05).(2)E조자서적사망솔(23.0%)고우A(0.8%)、B(0.9%)、C(1.7%)급D조(3.7%),차이균유통계학의의(P＜0.05);A、B、C、D조자서적사망솔의차승고,단차이무통계학의의(P＞0.05).(3)E조자서간、폐병리개변현저,간장특정성병리개변포괄간조직결구문란、간세포탁종、포질담염;다수간세포포질내출현지방변성,부분간세포고축,포질심염;간조직내견염세포침윤화점조상배사.폐특정성병리개변포괄폐세지기관관강변착、점막하층소혈관충혈;간질、폐포수종,폐포간격증후,포내、세지기관주중성립세포급림파세포침윤.C、D조상술병변정도차지,A、B조정상혹변화경미.(4)E조자서폐CYP1A1화간CYP1A2단백표체수평(분별위1.20±0.40급2.55±0.89)고우A조(0.77±0.36급2.08±0.31),량조비교,차이유통계학의의(P＜0.05).폐CYP1A1 mRNA표체,C(0.36±0.12)、D(0.41±0.08)、E조(0.43±0.11)고우A조(0.21±0.10),D、E조고우B조(0.28±0.10),분별비교,차이균유통계학의의(P＜0.05).간CYP1A2 mRNA표체,C(0.37±0.13)、D(0.36±0.14)、E조(0.43±0.16)고우A조(0.21±0.03),E조고우B조(0.24±0.11),분별비교,차이균유통계학의의(P＜0.05).결론 PM구유배태독성작용.초대제량PM아급성폭로가도치소서적불량임신결국;중、고제량PM폭로가도치암상관기인CYP1 A1화CYP1 A2표체적상조,가능대개체적후기발육유잠재적불량효응.
Objective To investigate subacute exposure of airborne particulate matter (PM) on pregnancy and fetal development in female mice. Methods Forty female and forty male ICR adult mice group (A), small (B) , middle (C) , large (D) or overdose (E) PM challenge groups (n = 8 - 11), and were administered with 30 μl of phosphate buffered solution (A) or resuspended standard PM SRM 1649a at 0.09 (B), 0.52 (C), 1.85 (D) or 69.2 (E) μg/μl, once per trid from d 0 till d 19 of pregnancy via instillation onto the base of the tongue. Fetal mice were harvested by cesarean section at the time when spontaneous delivery occurred. Body weight of the pregnant mice, gestational days, intrauterine survival and growth, hepatic and pneumonic histopathological changes of the fetal mice were investigated. Lung/body and liver/body weight ratios were calculated. Expressions of mRNA and protein of CYP1A1 in the fetal lung and CYP1 A2 in the fetal liver were assayed. Results (1) All of the pregnant mice survived pregnancy throughout the entire experiment. Body weight of the pregnant mice was not significantly different among all the groups at gestational d 1 and 7 (P ＞ 0.05), but significantly lower in group E [(41.8 ± 5.8) and (48.9 ± 8.9) g] than in group A [(45.9 ± 1.8) and (56.2 ± 4.9) g] at gestational d 14 and 18 (P ＜0.05). The gestational days were significantly decreased in group E [(19.3 ± 1.3) d] when compared with group A [(20.5 ± 0.7) d; P ＜ 0.05] and were not significantly different among groups A, B, C and D (P ＞ 0.05). Lung/body and liver/body weight ratios of the fetal mice were significantly increased in group E [(1.21 ±0.18) and (4.68 ±0.21)%] as compared with groups A, B, C and D (P＜0.05). (2)Mortality rates of the fetuses were significantly higher in group E (23.0%) than in groups A (0.8%), B (0.9%), C (1.7%) and D (3.7%) (P ＜ 0.05), but were not significantly different among groups A,B, C and D (P ＞ 0.05) despite of an increasing tendency. (3) Pathological changes in the liver and lung of the fetuses were conspicuous in group E. The fetal liver injury was histopathologically evidenced by deranged tissue structure, degenerated parenchyma of hepatic cells, and mildly stained cytoplasm. Adipose degeneration was represented by clear-boundary intracytoplasmic vacuoles in most of the liver cells, and cell pyknosis with heavily stained cytoplasm was observed in some of the liver cells. Inflammatory cell infiltration and focal necrosis were occasionally found in the hepatic tissue. The fetal lung exhibited bronchiole with narrow lumina, vascular engorgement in the submucosal layer, interstitial and alveolar edema, thickened alveolar septum, granulocyte and lymphocyte infiltrations within the pulmonary alveoli and around the bronchioles. The above pathological changes were lesser in groups C and D, and were not or least found in groups A and B. (4) Protein expressions of CYP1A1 in the fetal lung and CYP1A2 in the fetal liver were significantly increased in group E (1.20 ± 0.40 and 2.55 ± 0.89) when compared with group A (0.77 ±0.36 and 2.08 ±0.31) (P ＜ 0.05). mRNA expressions of CYP1A1 in the fetal lung were significantly increased in groups C (0.36 ±0.12), D (0.41 ±0.08) and E (0.43 ±0.11) compared with group A (0.21 ±0.10), and significantly increased in groups D and E compared with group B (0.28 ±0.10,P＜0.05). mRNA expressions of CYP1 A2 in the fetal liver were significantly increased in groups C (0.37 ±0.13), D (0.36 ±0.14) and E (0.43 ±0.16) compared with group A (0.21 ±0.03), and significantly increased in group E compared with group B (0.24± 0.11, P ＜ 0.05). Conclusions PM elicited embryotoxigenicity and resulted in adverse pregnancy outcomes in mice by intrauterine exposure of overdose PM. The expressions of cancer-related genes CYP1A1 and CYP1A2 were up-regulated in organs after the middle- and large-dose subacute exposure of PM, which may have a potential role on the future development.
