摘要
目的 研究甲状腺激素缺乏对发育期大鼠脑蛋白激酶C(PKC)活性的影响 ,以探讨甲状腺激素调节脑发育的机制。方法 以丙基硫氧嘧啶溶液灌胃造成大鼠围生期甲减模型 ,部分甲减仔鼠每日腹腔注射T4 2 μg/ 10 0g体重。收集 5天、15天和 2 5天的正常、甲减及T4 替代治疗仔鼠脑组织 ,测定脑组织胞液和膜PKC活性。结果 生后 5天、15天和 2 5天的甲减仔鼠脑胞液PKC活性较同日龄正常仔鼠明显升高〔出生后 5天 (P5 ) :(1.0 7± 0 .2 0 )vs (0 .45± 0 .0 4)nmol·min-1·mg蛋白 -1,P <0 .0 0 1;出生后 15天 (P15 ) :(2 .2 1± 0 .41)vs (1.0 3± 0 .2 0 )nmol·min-1·mg蛋白 -1,P <0 .0 1;出生后 2 5天 (P2 5 ) :(3 .49± 1.0 7)vs (1.72± 0 .6 7)nmol·min-1·mg蛋白 -1,P <0 .0 5〕 ;膜PKC活性也较同日龄正常仔鼠明显升高〔P5 :(1.45± 0 .2 1)vs (0 .37± 0 .0 5 )nmol·min-1·mg蛋白-1,P <0 .0 0 1;P15 :(3 .86± 1.0 4)vs (0 .80± 0 .2 2 )nmol·min-1·mg蛋白 -1,P <0 .0 1;P2 5 :(4 .6 1± 1.6 9)vs(1.2 7± 0 .30 )nmol·min-1·mg蛋白-1,P <0 .0 1〕 ;膜PKC活性与胞液PKC活性之比也明显升高〔P5 :(1.37± 0 .2 2 )vs (0 .82± 0 .13)nmol·min-1·mg蛋白 -1,P <0 .0 5 ;P15 :(1.76± 0 .39)vs (0 .
Objective To study the effect of thyroid hormone deficiency on activity of protein kinase C (PKC) in developing rat brain and to explore the mechanism of brain development regulated by thyroid hormone. Methods Perinatal hypothyroidism was induced by administering propylthiouracil (PTU) solution to the dams by gavage (1% PTU 2.5ml/day) beginning on embryonic day 15. Some pups were injected intraperitoneally with 2μg T 4·(100g body weight) -1 ·d -1 from the day of birth. Brain PKC activity was measured in the cytosolic and membrane fractions of normal pups and hypothyroidism pups without or with T 4 treatment. Results As compared to age matched controls, a very large increase was noticed in brain PKC activity in hypothyroid pups both cytosol 〔postnatal 5th days (P5):(1.07±0.20) vs (0.45±0.04)nmol·min -1 ·mg protein -1 ,P<0.001; postnatal 15th days (P15):(2.21±0.41) vs (1.03±0.20)nmol·min -1 ·mg protein -1 ,P<0.01; postnatal 25th days (P25):(3.49±1.07) vs (1.72±0.67)nmol·min -1 ·mg protein -1 ,P<0.05〕 and membrane fractions 〔P5: (1.45±0.21) vs (0.37±0.05)nmol·min -1 ·mg protein -1 ,P<0.001; P15: (3.86±1.04) vs (0.80±0.22)nmol·min -1 ·mg protein -1 ,P<0.01; P25: (4.61±1.69) vs (1.27±0.30)nmol·min -1 ·mg protein -1 ,P<0.01〕. The change of membrane PKC activity was more marked than that of cytosol, and hypothyroidism led to a higher ratio of membrane PKC activity to that in cytosol in relation to the age matched controls 〔P5: (1.37±0.22) vs (0.82±0.13)nmol·min -1 ·mg protein -1 ,P<0.05; P15: (1.76±0.39) vs (0.77±0.08)nmol·min -1 ·mg protein -1 ,P<0.01; P25: (1.31±0.15) vs (0.77±0.11)nmol·min -1 ·mg protein -1 ,P<0.05〕. The PKC activity both membrane and cytosol in T 4 injected pups was significantly lower than that in age matched hypothyroid pups. Conclusion Thyroid hormone deficiency during development may lead to increased activation of PKC in brain and translocation of the enzyme from cytosolic to membrane compartments, this may result in some disorders of brain such as neuron injury, collapse of growth cone, impairment of neurite outgrowth and synaptogenesis.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2000年第2期106-108,共3页
Chinese Journal of Endocrinology and Metabolism
基金
国家自然科学基金资助!(批准号39570347)
