摘要
目的观察长期高碘对大鼠海马神经细胞形态结构及细胞凋亡的影响,并探讨其作用机制。方法SD大鼠随机分为3组:对照组、高碘Ⅰ组、高碘Ⅱ组,分别以含碘量为5、5000、10 000μg/L的自来水及普通饲料喂养。6个月时检测血清总甲状腺激素(TT_3、TT_4)水平;光、电镜下观察神经细胞尼氏小体及超微结构改变;流式细胞仪检测细胞凋亡率及细胞周期的变化;分光光度法检测一氧化氮(NO)水平及一氧化氮合酶(NOS)活性:RT-PCR法检测凋亡相关基因bcl-2、bax mRNA表达。结果对照组、高碘Ⅰ组、高碘Ⅱ组血清TT_3、TT_4水平呈逐渐下降趋势。组间比较差异无统计学意义。高碘Ⅰ、Ⅱ组光镜下神经元尼氏小体模糊减少,胞质淡染。电镜下细胞核内染色质浓缩成块,聚集在核膜边缘,形成花瓣状、马蹄状等不规则形态,核膜内陷、包裹聚集的染色质形成凋亡小体。海马神经细胞凋亡率高碘Ⅰ、Ⅱ组均较对照组明显升高(P<0.01)。但高碘Ⅰ组、高碘Ⅱ组间比较未见明显差异(P>0.05)。与对照组相比,高碘Ⅰ、Ⅱ组S期细胞减少(P<0.01),G_2/M期增加(P<0.05),G_1期无明显变化(P>0.05)。高碘Ⅰ、Ⅱ组大鼠海马组织NOS活性及NO水平均明显低于对照组(P<0.01).bcl-2 mRNA表达降低(P<0.01)、bax mRNA表达升高(P<0.01),但高碘Ⅰ组、高碘Ⅱ组问未见明显改变(P>0.05)。结论长期高碘可诱导大鼠海马神经细胞凋亡,细胞周期改变;其机制可能与NOS活性、NO水平降低以及bax过度表达、bcl-2表达下调有关。
Objective To investigate the morphological structure and the mechanism of the apoptosis in rat hippocampus induced by high iodine, Methods An animal model of goiter was reconstructed in rat fed with water containing high level of iodine （the concentration of iodine were 5, 5000 and 10 000 μg/L individually） for six months. Rats were randomly divided into three groups： control group, high iodine group Ⅰ and high iodine group Ⅱ. Using radio-immunoassay, the serum thyroid hormones （TY3, TY4） were measured, Hippocampus morphological changes and uhrastructure were observed. The effect of excess iodine on apoptosis and cell cycle in hippocampus were detected using flow cytometry. The level of NO and the activity of NOS were determined with spectrophotometry. The expression of bcl-2 mRNA and bax mRNA were detected by RT-PCR techniques. Results The levels of serum thyroid hormones （TT3, TT4） was decreased gradually in turn of control group to high iodine groups, but there was no difference among three groups. The morphologic damage was found in the dentate gyrus of hippocampus,and the ratio of apoptosis was higher in hippocampus of high iodine groups than that in control group （P 〈 0.05）, but there was no differences between high iodine group Ⅰ and high iodine group Ⅱ （ P 〉 0.05）. Cell cycle show that S-phase cells decreased （P 〈 0,01）,GJM increased （P 〈 0.05）, no significant changes in G1 phase （P 〉 0.05）. The level of NO and NOS in the high iodine groups were lower than that in the control group. The expression of bcl-2 was lower and the expression of bax was higher as compared with those in the control group（P 〈 0.01 ）. Conclusions High iodine may induce the extensive apoptosis in hippocampus and cause the change of cell cycle via the mechanism of changing the expression of bcl-2 and bax and decreasing the activity of NOS and the level of NO.
出处
《中国地方病学杂志》
CAS
CSCD
北大核心
2007年第6期611-615,共5页
Chinese Jouranl of Endemiology
基金
辽宁省自然科学基金(20062001)
