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目的:本研究利用经典的新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)动物模型,观察应用胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)前后脑白质微管相关蛋白(microtubule-associated protein,MAP)总Tau水平的改变,探讨新生大鼠HIBD早期应用IGF-1后总Tau蛋白水平的改变与脑损伤的关系。方法:7日龄Wistar大鼠随机分为假手术组、模型组和用药组,分别给予同等剂量的磷酸盐缓冲液PBS(假手术组、模型组)和IGF-1(用药组)腹腔注射,给药后24小时采集标本。HE及嗜银染色法光镜下分别观察脑神经细胞和神经纤维的病理变化;免疫组化和Western Blot方法检测脑白质总Tau蛋白水平的表达。结果:(1)假手术组HE染色后脑白质神经细胞形态正常,轮廓清晰,核仁核膜明显,大小无变化,未见明显损伤性改变;模型组新生大鼠脑组织HE病理检测可见明显的毛细血管出血,细胞核固缩、核碎裂明显,模型建立成功。(2)假手术组脑神经细胞染色分布均匀,树突轴突沿其走行分布;模型组嗜银染色示神经纤维增粗,部分神经纤维呈缠结状;用药组神经纤维稍增粗,未见明显的神经纤维缠结。(3)免疫组化和WesternBlot检测用药组总Tau蛋白的值低于模型组(p(0.05),但高于假手术组(p(0.05)。结论:HIBD新生大鼠早期应用IGF-1对脑白质神经细胞和神经纤维具有保护作用,总Tau蛋白水平下降。
Objective: In this study, a classic model of hypoxic-ischemic brain damage (HIBD) was used to observe the effects of insulin-like growth factor-1 (IGF-1) The changes of total Tau in microtubule-associated protein (MAP) before and after cerebral ischemia in rats and explore the relationship between the changes of total Tau protein level and brain injury after early application of IGF-1 in neonatal rats. Methods: The 7-day-old Wistar rats were randomly divided into sham-operation group, model group and treatment group. The rats were given PBS (sham-operation group, model group) and IGF-1 Twenty four hours after administration, specimens were collected. The pathological changes of brain nerve cells and nerve fibers were observed under HE staining and argyrophil staining. The total Tau protein expression was measured by immunohistochemistry and Western Blot. Results: (1) HE staining showed that the morphology of brain white matter neurons in sham operation group was normal, the outline was clear, the nuclear membrane of nucleolus was obvious, the size did not change, and no obvious damage was found. In model group, HE staining of brain tissue showed obvious Capillary hemorrhage, nuclear pyknosis, nuclear fragmentation significantly, the model was established. (2) In the sham-operated group, the distribution of neuronal cells was uniform and the axons of dendrites were distributed along the line. The argyrophilic staining in the model group showed that the nerve fibers were thick and some of the nerve fibers were entangled. The nerve fibers in the sham- See obvious neurofibrillary tangles. (3) Immunohistochemistry and Western Blot showed that total Tau protein in the treatment group was lower than that in the model group (p <0.05), but higher than that in the sham operation group (p <0.05) .Conclusion: IGF- White matter nerve cells and nerve fibers have a protective effect, the total Tau protein levels decreased.