本文關(guān)鍵詞： 鎘穩(wěn)定同位素 胎盤 胎鼠 骨骼 臍血　出處：《山西醫(yī)科大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：目的探討鎘是否通過胎盤屏障到達(dá)胎鼠體內(nèi)影響胎鼠生長發(fā)育,為進(jìn)一步研究鎘發(fā)育毒性的機(jī)制提供資料。 方法雌性SPF級SD大鼠40只隨機(jī)分為2組,即對照組和染鎘組,每組20只,對照組大鼠皮下注射去離子水,染鎘組大鼠皮下注射40μg/kg體重112Cd2+溶液,每天一次,連續(xù)染毒45～58天。第24天開始將所有雌性大鼠與健康雄性大鼠同籠交配,次日晨查到陰栓或精子,定為懷孕第0天。懷孕第20天時對試驗(yàn)大鼠乙醚麻醉后進(jìn)行解剖,取母鼠和胎鼠主要臟器,具體檢測項(xiàng)目和方法如下： (1)鎘在母鼠體內(nèi)的分布：母鼠尿、母鼠血用原子吸收光譜儀(AAS)測定鎘含量；用電感耦合等離子體質(zhì)譜儀(ICP-MS)測母鼠腦、心臟、肝臟、腎臟和胎盤中鎘含量。檢測母鼠血生化指標(biāo)、雌二醇(E2)以及尿中視黃醇結(jié)合蛋白(URBP).微量白蛋白(MAU)和尿肌酐(CREA)等指標(biāo)。統(tǒng)計(jì)吸收胎率、死胎率、活胎率。 (2)鎘對子代影響的研究：胎鼠生長發(fā)育指標(biāo)的分析。用AAS測臍帶血鎘含量,研究鎘是否能夠通過胎盤屏障；用ICP-MS測胎鼠腦、心臟、肝臟、腎臟的鎘含量,研究鎘在胎鼠各臟器中的分布。鎘對胎鼠骨骼形成的影響：胎鼠去掉兩側(cè)頸部皮膚和脂肪,經(jīng)過固定、透明、染色、透明脫色后在解剖顯微鏡下觀察胎鼠骨骼形態(tài),研究低劑量鎘是否能夠引起胎鼠骨骼畸形。 (3)鎘對母鼠和胎鼠臟器的病理學(xué)影響：取SD大鼠母鼠和胎鼠的腦、心臟、肝臟、腎臟,以及胎盤對其進(jìn)行固定、脫水、包埋、切片和染色后,在普通光學(xué)顯微鏡下檢查以上臟器的細(xì)胞形態(tài)學(xué)改變,研究低劑量鎘是否引起母鼠和胎鼠臟器的病理學(xué)改變。 結(jié)果(1)鎘在母鼠體內(nèi)的分布：①母鼠體內(nèi)鎘分布以及鎘負(fù)荷：染鎘組大鼠腦、心臟、肝臟、腎臟、胎盤的鎘含量與對照組相比差異均有統(tǒng)計(jì)學(xué)意義(P0.01)。染毒第24天和孕期第20天的染鎘組母鼠血鎘含量均高于對照組血鎘,差異均有統(tǒng)計(jì)學(xué)意義(P0.01)。染鎘組大鼠尿鎘含量僅在染毒至孕期20天時高于對照組尿鎘含量,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。②母鼠肝、腎功能指標(biāo)：在染毒第24天和妊娠第20天時,母鼠尿視黃醇結(jié)合蛋白含量與對照組之間的差異有統(tǒng)計(jì)學(xué)意義(P0.01)。染毒第24天和孕第20天時染鎘組MAU與對照組MAU之間的差異尚無統(tǒng)計(jì)學(xué)差異(P0.05)。孕第20天時實(shí)驗(yàn)組大鼠血中僅AST和CREA與對照組血中AST和CREA之間差異有統(tǒng)計(jì)學(xué)意義(P0.01)。③染鎘組吸收胎率增高,活胎率降低,母鼠孕20天的雌二醇水平下降,差異均有統(tǒng)計(jì)學(xué)意義(P0.01)。 (2)鎘對子代的影響研究：①染鎘組胎盤重量、胎鼠重與對照組相比顯著降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。②染鎘組胎鼠臍血血鎘含量是對照組臍血血鎘含量的11倍之多,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。③染鎘組胎鼠腦、心、肝、腎鎘含量均較對照組相應(yīng)臟器鎘含量增加,且與對照組之間的差異均有統(tǒng)計(jì)學(xué)意義(P0.01)。④染鎘組胎鼠異常率顯著高于對照組,主要表現(xiàn)有鼠掌骨未骨化、胸骨骨化不全和胸骨未骨化。 (3)母鼠和胎鼠臟器的病理學(xué)改變：母鼠肝臟、腎臟的病理改變率顯著高于對照組(P0.01),主要表現(xiàn)為腎臟輕度彌漫性腎小管上皮細(xì)胞空泡化和肝細(xì)胞水腫肝細(xì)胞腫脹等病變。染鎘組和對照組胎盤和胎鼠臟器均未見明顯病理改變。 結(jié)論應(yīng)用穩(wěn)定同位素鎘112Cd按40μg112Cd2+/kg體重劑量對雌性SD大鼠進(jìn)行皮下注射染毒,染毒周期覆蓋雌性大鼠四個動情周期(24天)和孕期20天。連續(xù)鎘染毒可以引起染鎘組吸收胎率增高、活胎率下降、胎盤重量和胎鼠重降低,降低孕鼠雌二醇水平。低劑量鎘可以通過大鼠胎盤屏障并分布到胎鼠體內(nèi)的腦、心臟、肝臟和腎臟等多個臟器。并且本實(shí)驗(yàn)條件下鎘可以引起胎鼠骨骼畸形,阻礙骨骼的形成,主要有胎鼠掌骨未骨化、胸骨骨化不全和胸骨未骨化等。在母鼠體內(nèi)臟器的分布由高到低依次是肝臟、腎臟、腦、胎盤、心臟。并引起孕鼠肝臟、腎臟功能的損傷和肝腎的病理改變。本試驗(yàn)?zāi)M大鼠一代繁殖實(shí)驗(yàn),建立低劑量染毒模型,與人體的實(shí)際接觸比較吻合。
[Abstract]:Objective To study the effect of cadmium on the growth and development of fetal mice through placental barrier , and to provide information for further study on the mechanism of cadmium development toxicity . Methods Forty - four female SPF SD rats were randomly divided into 2 groups : control group and Cd - stained group . 20 rats in each group were injected subcutaneously with deionized water and 40 渭g / kg body weight of 112 Cd 2 + solution . The female rats and healthy male rats were injected subcutaneously once a day for 45 - 58 days . ( 1 ) Distribution of cadmium in female mice : determination of cadmium content by atomic absorption spectrometry ( AAS ) in mother rat urine and maternal rat blood ; determination of cadmium content in brain , heart , liver , kidney and placenta by inductively coupled plasma mass spectrometer ( ICP - MS ) . Blood biochemical indexes , estradiol ( E2 ) , and retinol binding protein ( URBP ) in urine were measured . ( 2 ) The effect of cadmium on children ' s growth and development was studied . The content of cadmium in cord blood was measured by AAS . The cadmium contents of fetal rat brain , heart , liver and kidney were measured by ICP - MS . The effects of Cd on the skeletal formation of fetal mice were studied . ( 3 ) The pathological effects of cadmium on the organs of mother and fetal rats were studied : the brain , heart , liver , kidney and placenta of SD rats were fixed , dehydrated , embedded , sectioned and stained . The morphological changes of the above organs were examined under common optical microscope . Results ( 1 ) The distribution of cadmium in mother rat was significantly higher than that of control group ( P0.01 ) . There was no significant difference between the contents of cadmium in the brain , heart , liver , kidney and placenta of the rats in the control group ( P0.01 ) . ( 2 ) The effect of cadmium on filial generation was as follows : ( 1 ) The placental weight of cadmium - stained group and the weight of fetal mice were significantly lower than those in control group ( P0.01 ) . 鈶，

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