孕期不同阶段铅暴露时大鼠胎盘基质金属蛋白酶-9及组织抑制剂-1的表达

Effects of lead exposure during different gestation period to rat placenta and the expression of matrix metalloproteinase-9 and tissue inhibitor of metaUoproteinase-1

目的观察不同阶段铅暴露对孕鼠胎盘基质金属蛋白酶．9（MMP-9）及其组织抑制剂-1（TIMP-1）表达的影响，探讨铅的胎盘毒性机制。方法108只大鼠随机分为4组，每组27只（雌雄比为2：1）合笼饲养，于孕期不同阶段饮服0．025％醋酸铅。对照组孕期全程（1-20d）饮服蒸馏水；实验A组孕早期（1～10d）饮服醋酸铅，孕后期（11—20d）饮服蒸馏水；实验B组孕早期（1—10d）饮服蒸馏水，孕后期（11—20d）饮服醋酸铅；实验C组孕期全程（1．20d）饮服醋酸铅。孕末期腹腔静脉取血，原子吸收光谱法测定血铅，免疫组化法测定胎盘滋养层细胞MMP-9和TIMP-1的表达。结果（1）对照组孕鼠孕末期平均血铅水平为（0．04±0．01）μMol／L，实验组孕鼠孕末期平均血铅水平均高于0．483μMol／L，实验C组血铅水平最高；（2）MMP-9和TIMP-1在胎盘组织中的表达部位主要位于滋养层细胞胞质；（3）胎盘滋养层细胞MMP-9表达4组间总体比较差异有统计学意义（X^2=28．381，P〈0．01），血铅水平最高的实验C组阳性表达率最低，与对照组比较差异有统计学意义（P〈0．05）；（4）胎盘滋养层细胞TIMP-1表达4组间总体比较差异有统计学意义（X^2=18．177，P〈0．05），表达强度以实验C组最高，实验A组次之，与对照组比较差异有统计学意义（P〈0．05）。结论孕期MMP-9和TIMP-1的表达部位主要位于胎盘滋养层细胞。铅中毒程度越重，MMP-9和TIMP-1的表达强度改变越明显。MMP-9和TIMP-1的表达失衡可能是铅致胎盘损伤的病理机制之一。

Objective To explore the pathogenesis of placenta toxicity of lead exposure during different gestation periods by testing the blood lead level and the expression of matrix metalloproteinase-9（MMP-9） and tissue inhihitorof metalloproteinase-l（TIMP-1） in rat placenta. Melhods 108 Wistar rats（72 female, 36 male） were randomly divided into four groups. All rats were orally fed with 0.025 % lead acetate during different gestation periods. Blood was obtained from the abdominal vena eava and the lead level in maternal blood was measured by means of atomic absorption spectrometry at the end of the pregnancy. The expression of MMP-9 and TIMP-1 in rat placenta was tested by means of immunohistochemistry. Results （ 1 ）The blood lead level in the end of pregnancy was 0.04μmol/L ± 0.01 in control group, while in experimental groups the blood lead levels were all higher than 0.483μmol/L, among them the highest blood lead level was in experimental group C. （2） The expression of MMP-9 and TIMP-1 mostly distributed in trophoblastic cells. （3）The expression of MMP-9 had significant difference in four groups（ X^2 = 28.381, P 〈 0.01） .The expression of MMP-9 was significantly reduced in experimental group C （the highest blood lead level） compared with control group. （4） The expression of TIMP-1 had significant difference in four groups （ X^2 = 18.177, P 〈 0.05 ）. The expression of TIMP- 1 was significantly increased in experimental group A, C compared with control group. Conclusions The expression of MMP-9 and TIMP-1 in rat placenta mostly distributed in trophoblasfic cells. They would change when the degree of lead poisoning was more serious. The imbalance of expression of MMP-9/TIMP- 1 may play an important role in pathogenesis of placenta toxicity of lead exposure.