不同孕期铅暴露对大鼠妊娠结局及胎盘MMP-9、TIMP-1表达的影响
Effects of Lead Exposure to Rat during Different Gestation Period on Pregnant Outcome and Expression of Matrix Metalloproteinase-9(MMP-9) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) in Rat Placenta
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摘要:
目的 通过观察Wistar大鼠孕期不同时段铅暴露对妊娠结局及胎盘基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子-1(TIMP-1)的表达影响,评价孕早期、孕后期及孕全程铅暴露的毒性特点及毒性机制。 方法 108只Wistar大鼠随机分为4组,每组27只(雌:雄为2:1),用0.025%醋酸铅对各实验组的孕鼠通过自由饮服的方式染毒。实验A组:孕早期(1~10 d)饮服0.025%醋酸铅,孕后期(11~20 d)饮服蒸馏水;实验B组:孕早期(1~10 d)饮服蒸馏水,孕后期(11~20 d)饮服0.025%醋酸铅;实验C组:孕期全程(1~20 d)饮服0.025%醋酸铅。根据大鼠孕期3周推算,足月进行麻醉剖腹取胎,观察胎盘及仔鼠体重、身长、尾长、仔鼠数等;同时采集腹腔静脉血,用原子吸收光谱仪测定各组大鼠孕末期血铅水平。免疫组化法测定胎盘滋养细胞MMP-9、TIMP-1的表达。 结果 实验组孕末期血铅水平与对照组比较差异均有统计学意义(P < 0.01)。各组胎盘重量及仔鼠体重、身长、尾长差异也有统计学意义(P < 0.01),其中实验C组最低,分别为(0.31& #177;0.13) g、(2.08& #177;0.88) g、(2.37& #177;0.32) cm、(0.98& #177;0.09) cm。血铅水平与胎盘重量呈负相关(r=-0.652,P < 0.01)。孕全程染铅组胎盘MMP-9表达下降,TIMP-1表达增强。 结论 孕期不同时段铅暴露导致不同的妊娠结局。孕全程染铅的孕末期血铅水平最高,对胎盘及仔鼠影响最大。胎盘MMP-9表达下降、TIMP-1表达增强可能是铅致胎盘损伤的病理机制之一。 Abstract:Objective To Study the pathogenesis of placenta toxicity of lead exposure during different gestation period by observing the pregnant outcome and testing the expression of matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in placenta. Methods Total of 108 Wistar rats divided into four groups with 27 each randomly. Sex ratio was 2:1(male/female). Fed with 0.025% lead acetate solution, ad libertum, during different period of gestation. Group A were fed with 0.025% lead acetate in early gestation(1-10 d). Group B were fed with 0.025% lead acetate in late gestation (11-20 d). Group C were fed with 0.025% lead acetate throughout whole gestation (1-20 d). Atomic absorption spectrophotometer was used to measured the blood lead concentration at end of pregnancy. The pregnant rats were necrospied at the end of gestation(three weeks)under aenesthia. Placenta were observed and blood sample was taken from abdominal vein. The number of pups, their body weight、body length、tail length、placenta weight were measured. The expression of MMP-9 and TIMP-1 in rat placenta was tested by means of immunohistochemistry. Results The blood lead level of experimental groups was significant different(P < 0.01)versus the blood lead level of control. There were significant differences among placenta weight, body weight of pups, body length and tail length of pups in different groups (P < 0.01). Among them experimental group C was the lowest (0.31& #177;0.13)g,(2.08& #177;0.88)g,(2.37& #177;0.32)cm,(0.98& #177;0.09)cm. Maternal blood lead level was negatively correlated to placenta weight(r=0.652, P < 0.01). The expression of MMP-9 was significantly reduced and TIMP-1 was significantly increased versus the control group. Conclusion Lead exposure to rat during different gestation period lead to different pregnant outcome. Lead exposure throughout the gestation cause the highest blood lead concentration at the end of the pregnancy, and the placenta, pups were most seriously effected. Changing of the MMP-9 and TIMP-1 expression in placenta may play one of the roles in pathogenesis of placenta toxicity of lead exposure.
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