齐拉西酮对小胶质细胞活化的作用及其机制

发布时间：2019-01-09 14:19

【摘要】：目的在在体动物系统性炎症模型中探索非典型抗精神病药物齐拉西酮对脂多糖(LPS)诱导的小胶质细胞活化的作用及机制。方法雄性SD大鼠77只,随机分为动物炎症模型组(n=35)、探索药物浓度组(n=24)以及药物干预组(n=18)。动物炎症模型组分别于腹腔注射LPS后0、2、4、8、12 h将大鼠处死,以生理盐水组为对照,通过Western blotting方法检测脑纹状体诱导性一氧化氮合酶(iN OS)蛋白表达量;探索药物浓度组分为LPS组(5 mg/kg)、齐拉西酮(1、2.5、5 mg/kg)处理后注射LPS(5 mg/kg)组、舒必利(10、25、40 mg/kg)处理后注射LPS(5 mg/kg)组、对照组(相同体积DMSO,5%),Western blotting检测不同药物浓度下纹状体部位iN OS蛋白表达量;药物干预组分为LPS组(5 mg/kg)、齐拉西酮(5 mg/kg)处理后注射LPS(5 mg/kg)组、对照组(相同体积DMSO,5%),通过RT-PCR方法检测纹状体部位iN OS mRNA表达,Oxyblot方法检测羰基化蛋白的表达。结果 LPS(5 mg/kg)可以引起动物炎症模型组中纹状体部位小胶质细胞iN OS蛋白表达的增多,且在4 h时iN OS蛋白表达量达到最高(P0.05);探索药物浓度组中,高剂量齐拉西酮(5 mg/kg)可以明显抑制LPS引起的纹状体部位iN OS蛋白表达(P0.05);药物干预组中齐拉西酮(5 mg/kg)可以明显抑制LPS引起的纹状体部位iN OS mRNA以及羰基化蛋白的表达(P0.05)。结论非典型抗精神病药物齐拉西酮可能通过抑制小胶质细胞活化关键酶iN OS及蛋白氧化产物(羰基化蛋白)的表达,对小胶质细胞的活化产生抑制作用。
[Abstract]:Objective to explore the effect and mechanism of ziprasidone, an atypical antipsychotic drug, on the activation of lipopolysaccharide (LPS) -induced microglia in animal models of systemic inflammation. Methods Seventy-seven male SD rats were randomly divided into the inflammatory model group (n = 35), the drug concentration group (n = 24) and the drug intervention group (n = 18). The rats in the inflammatory model group were killed at 12 h after intraperitoneal injection of LPS, and the expression of inducible nitric oxide synthase (iN OS) protein in the striatum was detected by Western blotting method. The drug concentration components were divided into LPS group (5 mg/kg), ziprasidone group (12 2. 5 mg/kg) treated with LPS (5 mg/kg), sulpiride group (10 25 mg/kg) and LPS (5 mg/kg) group, and control group (DMSO, of the same volume). The expression of iN OS protein in striatum was detected by 5%), Western blotting. The drug intervention group was divided into LPS group (5 mg/kg), ziprasidone group (5 mg/kg) treated with LPS (5 mg/kg) and control group (same volume DMSO,5%). IN OS mRNA expression in striatum was detected by RT-PCR. The expression of carbonylated protein was detected by Oxyblot. Results LPS (5 mg/kg) could increase the expression of iN OS protein in the striatum, and the expression of iN OS protein reached the highest level at 4 h (P0.05). In the drug concentration group, high dose of ziprasidone (5 mg/kg) significantly inhibited the expression of iN OS protein in striatum induced by LPS (P0.05). Ziprasidone (5 mg/kg) significantly inhibited the expression of iN OS mRNA and carbonylation protein in striatum induced by LPS in the drug intervention group (P0.05). Conclusion Ziprasidone, an atypical antipsychotic drug, may inhibit the activation of microglia by inhibiting the expression of iN OS, a key enzyme of microglia activation, and the protein oxidation product (carbonylation protein).
【作者单位】：上海交通大学医学院附属精神卫生中心;
【基金】：国家自然科学基金青年项目(81101002) 上海市公共卫生优秀学科带头人培养计划~~
【分类号】：R749.3

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