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目的观察黑质部位炎症反应对多巴胺能神经元的长时程毒性作用,探讨脑内炎症反应在黑质多巴胺能神经元慢性变性过程中的作用。方法健康SD雄性大鼠28只,随机分为生理盐水组和10μg、25μg、50μg脂多糖组。定位注射生理盐水或脂多糖入右侧脑室,术后24周观察大鼠行为学改变,免疫组织化学染色观察黑质部位小胶质细胞的激活情况及酪氨酸羟化酶阳性神经元的变化。结果1.大鼠行为学观察显示,10μg、25μg和50μg脂多糖组大鼠的平均运动速度与对照组相比,差异无统计学意义。2.OX-42免疫组织化学染色显示,10μg和25μg脂多糖组大鼠黑质部位小胶质细胞激活明显。50μg脂多糖组大鼠黑质部位小胶质细胞激活不明显。3.酪氨酸羟化酶免疫组织化学染色显示,10μg和25μg脂多糖组大鼠黑质酪氨酸羟化酶阳性神经元与对照组相比,胞体变小,突起减少甚至消失,染色变浅;50μg脂多糖组大鼠酪氨酸羟化酶阳性神经元形态与对照组相比没有明显改变。4.酪氨酸羟化酶阳性细胞计数显示,10μg和25μg脂多糖组大鼠与对照组比较,分别减少15.5%(P<0.01)和20.1%(P<0.01);50μg脂多糖组大鼠与对照组比较没有统计学差异。结论脑室注射脂多糖引发的脑内炎症可导致黑质多巴胺能神经元变性,这一过程呈慢性迟发性;同时,低剂量脂多糖激活小胶质细胞对黑质多巴胺能神经元的慢性毒性作用更为明显;该病理过程较好地模拟了帕金森病的发病特点。
OBJECTIVE: To observe the long-term toxicity of dopaminergic neurons in substantia nigra inflammatory reaction and to explore the role of inflammatory reaction in the process of chronic degeneration of dopaminergic neurons in substantia nigra. Methods Twenty-eight healthy SD male rats were randomly divided into normal saline group and 10μg, 25μg and 50μg lipopolysaccharide groups. Targeted injection of saline or lipopolysaccharide into the right ventricle, behavioral changes observed 24 weeks after operation, immunohistochemical staining of substantia nigra microglia activation and tyrosine hydroxylase-positive neurons . The results of behavioral observation in rats showed that the average speed of rats in 10μg, 25μg and 50μg lipopolysaccharide group had no significant difference compared with the control group. OX-42 immunohistochemical staining showed that the activation of microglia in substantia nigra of rats in 10μg and 25μg lipopolysaccharide groups was obvious. The activation of microglia in substantia nigra of 50μg lipopolysaccharide group was not obvious. Tyrosine hydroxylase immunohistochemical staining showed that 10μg and 25μg lipopolysaccharide group of nigrosine tyrosine hydroxylase-positive neurons compared with the control group, the cell body becomes smaller, the protrusions reduce or even disappear, staining Shallow; 50μg lipopolysaccharide group tyrosine hydroxylase positive neurons morphology compared with the control group did not change significantly. The number of tyrosine hydroxylase positive cells showed that the rats in 10μg and 25μg lipopolysaccharide groups decreased 15.5% (P <0.01) and 20.1% (P <0.01) Compared with the control group no statistical difference. Conclusion Intracerebral injection of lipopolysaccharide-induced intracerebral inflammation can lead to degeneration of substantia nigra dopaminergic neurons, which is delayed and chronic. At the same time, chronic toxicity of microglia to microdial neurons in substantia nigra is inhibited by low dose lipopolysaccharide The role is more obvious; the pathological process better simulates the onset of Parkinson’s disease characteristics.