论文部分内容阅读
目的探讨脂多糖(lipopolysaccharide,LPS) 预处理对脂多糖所致中脑脑片多巴胺能神经元炎性损伤的影响及其可能的机制。方法建立大鼠中脑脑片体外培养体系,于体外培养 14 d 后以不同剂量脂多糖(0、1、3、6及10 ng/mL)预处理24 h,然后用大剂量脂多糖(100 ng/mL)作用72 h,观察脂多糖预处理对脑片乳酸脱氢酶(lactic aciddehydrogenase,LDH)活性的影响。通过免疫组化检测酪氨酸羟化酶(Tyrosine hydroxylase,TH)和 OX-42 的阳性细胞数变化,应用酶联免疫吸附法测定培养液上清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。结果 100 ng/mL脂多糖作用72 h后引起脑片TH阳性细胞数从对照组的191±12减少到46±4,LDH活性明显升高(P < 0.01),小胶质细胞大量激活,TNF-α水平显著增高(P < 0.01)。脂多糖预处理能减少神经细胞的丢失(3 ng/mL和6 ng/mL的LPS 处理后TH阳性细胞数分别为126±12和180±13),降低脑片LDH活性(P < 0.05),并有效地抑制小胶质细胞的激活,明显减少TNF-α的生成(P < 0.05)。结论小剂量脂多糖预处理可改善脂多糖对大鼠中脑脑片多巴胺能神经元的损伤,其作用机制可能是通过抑制小胶质细胞的激活,减少TNF-α的释放,减轻炎症反应对神经元的损伤。这种保护作用可为帕金森氏病的治疗提供新思路。
Objective To investigate the effect of lipopolysaccharide (LPS) preconditioning on dopaminergic dopaminergic neuron injury induced by lipopolysaccharide and its possible mechanism. Methods Rat brain slices were cultured in vitro and pretreated with different doses of lipopolysaccharide (0, 1, 3, 6, 10 ng / mL) for 14 days and then treated with high dose lipopolysaccharide ng / mL) for 72 h. The effect of lipopolysaccharide preconditioning on the activity of lactic acid dehydrogenase (LDH) in the brain slices was observed. The changes of positive cells of tyrosine hydroxylase (TH) and OX-42 were detected by immunohistochemistry. The expression of tumor necrosis factor-α TNF-α) levels. Results After 100 ng / mL lipopolysaccharide treatment for 72 h, the number of TH positive cells in brain slices decreased from 191 ± 12 to 46 ± 4 in control group, LDH activity increased significantly (P <0.01), microglial cells were activated in large quantities, TNF -α levels were significantly higher (P <0.01). Lipopolysaccharide pretreatment reduced the loss of nerve cells (TH positive cells were 126 ± 12 and 180 ± 13 at LPS treatment of 3 ng / mL and 6 ng / mL, respectively) and LDH activity (P <0.05) And effectively inhibited microglial activation, significantly reducing TNF-α production (P <0.05). Conclusions Low-dose lipopolysaccharide pretreatment can improve the damage of dopaminergic neurons in rat midbrain brain by lipopolysaccharide. The mechanism may be through inhibiting the activation of microglia, reducing the release of TNF-α and reducing the inflammatory reaction Neuronal damage. This protective effect can provide new ideas for the treatment of Parkinson’s disease.