碘缺乏、甲状腺功能减退对仔鼠海马RKC活性及表达的影响

THE EFFECT ACTIVITY OF PROTEIN KINASEC AND EXPRESSION OF C-FOS AND C-JUN IN DEVELOPING HIPPOCAMPUS OF IODINE DEFICIENCY AND HYPOTHYROID RAT OFFSPRINGS.

目的 :研究碘缺乏、甲状腺功能减退对仔鼠海马蛋白激酶C活性的影响 ,并测定碘缺乏、甲状腺功能减退大鼠仔鼠海马组织c -fos、c-jun的表达 ,以探讨碘缺乏、甲状腺功能减退调节脑发育的机制。方法 :分别选用低碘饲料及他巴唑诱导建立低碘及甲减大鼠动物模型 ,收集生后 30d时仔鼠海马组织 ,测定海马细胞浆、细胞膜PKC活性。免疫组织化学S -P法染色 ,观察生后 30d时低碘组、甲状腺功能减退组 (甲减组 )及对照组大鼠仔鼠海马c-fos、c -jun表达情况并进行图像分析。结果 :生后 30d低碘组和甲减组仔鼠海马胞液PKC活性略低于对照组 ,而胞膜PKC活性稍高于对照组 ,低碘组、甲减组仔鼠海马胞膜PKC活性与胞浆PKC活性比值 (1. 4 1± 0 .12 ,1. 19± 0 . 14 )较对照组 (0 . 6 5± 0. 0 9)升高 ,差异有统计学意义 (P <0 .0 1)。生后 30天低碘组和甲减组仔鼠海马组织c -fos、c-jun灰度值均显著高于对照组P <0 .0 1) ,提示其表达水平明显降低。结论 :碘缺乏、甲状腺功能减退可引起仔鼠海马胞浆PKC向胞膜的转运 ,并可降低仔鼠海马组织原癌基因c -fos、c-jun表达 ,进而影响神经系统及智力发育 ,可能是低碘、甲减引起海马损害导致学习记忆功能减退的机制之一。

Objective:To study the effect of activity of protein kinase C(PKC)and m easure the expression of c-fos and c-jun in developing hippocampus of iodine def iciency and hypothyroid rat offsprings and to explore the mechanism of brain dev elopment regulated by iodine deficiency and hypothyroid.Methods:T he model of de ficient iodine and hypothyroid rats were established by pre-treatment with meth i mazole and shortage of iodines feed respectively.Hippocampus PKC activity was m easured in the cytoplasm and plasmalemma fractions of deficient iodine.The expr ession of c-fos and c-jun in hip pocampus tissu e on the postnatal thirtieth day were studied from hypothyroidism and control gr oups by means of S-P immunohistochemic al technique and micrograph analyses system.Results:The PKC activ ity of cytoplas m in deficient iodine and hypothyroidism groups were lower than the control grou ps and the PKC activity of plasmalemma are higher than control groups .As compar ed to age-matched controls(0.65±0.09),hypothyroidism led to a significantly higher ratio of membrane PKC activity to that in cytosol (1.41±0.12, 1.19±0 .14)(P<0.01).The means of average gray value of c-fos and c-jun in the io dine deficiency and hypothyroid groups on the postnatal thirtieth day were signific antly higher than that in the control group (P<0.01).Conclusions :Shortage of iodine and hypothyroidism during development may lead to translocation of the PK C from cytoplasm to plasmalemma and impair the expression of both c-fos and c-ju n of the offsprings,and may influence the growth of nerves and intelligence.It m ay result in some damages of hippocampus and decline of study and memory.