发育期慢性铅暴露对大鼠血浆、脑脊液和海马中瘦素表达的影响

Influence of chronic lead exposure in rats during the developmental stage on expression of leptin in plasma, cerebrospinal fluid, and hippocampus

摘要:

目的 研究发育期铅暴露对大鼠血浆、脑脊液和海马中瘦素表达的影响，探索瘦素是否和铅暴露引起的认知损伤机制有关。方法 通过在大鼠饮水中添加醋酸铅建造慢性铅暴露后大鼠认知损伤模型，根据饮水中醋酸铅的浓度可分为对照组 （0 ppm）、低铅组 （50ppm）、中铅组 （200ppm） 和高铅组 （1000ppm），每组16只。采用原子吸收光谱法检测各组大鼠血浆、脑脊液和海马中铅含量；ELISA法检测大鼠血浆和脑脊液中的瘦素水平；免疫组化法观察瘦素在海马组织中的分布；Western blot法对大鼠海马中瘦素蛋白水平进行相对定量分析。结果 与对照组相比，铅暴露组大鼠血浆、脑脊液和海马中铅含量均升高，而血浆和脑脊液中瘦素水平均下降 （P < 0.05）。免疫组化结果显示，瘦素主要分布于海马CA区锥体神经细胞胞浆中。Western blot结果显示，与对照组相比，3个铅暴露组大鼠海马中瘦素蛋白表达水平略升高，但差异均无统计学意义 （P > 0.05）。结论 铅暴露可使大鼠血浆和脑脊液瘦素水平降低，这可能与铅暴露引起大鼠认知能力损伤的机制有关。

Abstract:

Objective To investigate the influence of lead exposure in rats during the developmental stage on the expression of leptin in plasma, cerebrospinal fluid, and hippocampus, as well as investigating whether leptin is associated with the mechanism of cognitive impairment induced by lead exposure. Methods The rat model of cognitive impairment after chronic lead exposure was established by adding lead acetate into drinking water. According to the concentration of lead acetate in drinking water, the rats were divided into control (0 ppm), low-lead (50 ppm), medium-lead (200 ppm), and high-lead groups (1000 ppm), with 16 rats in each group. Atomic absorption spectrometry was used to measure the content of lead in the plasma, cerebrospinal fluid and hippocampus. ELISA was used to measure the level of leptin in the plasma and cerebrospinal fluid. Immunohistochemistry was used to observe the distribution of leptin protein in the hippocampus. Western blot was used for relative quantification of leptin proteins in the hippocampus. Results Compared with the control group, the lead exposure groups showed significant increases in the content of lead in blood, cerebrospinal fluid, and hippocampus (P < 0.01), as well as significant reductions in the levels of leptin in plasma and cerebrospinal fluid (P < 0.05). The results of immunohistochemical staining showed that leptin was mainly distributed in the cytoplasm of pyramidal neurons in the hippocampal CA region. The results of Western blot showed that compared with the control group, the three lead exposure groups showed a slight increase in the protein expression of leptin in the hippocampus (P > 0.05). Conclusions Lead exposure can reduce the levels of leptin in plasma and cerebrospinal fluid in rats, which may be associated with the mechanism of cognitive impairment induced by lead exposure.