摘要
背景:脑星形胶质细胞肿胀是肝衰竭时脑水肿的特征,但其机制尚未完全阐明。目的:研究代谢型谷氨酸受体1亚型(mGluR1)选择性拮抗剂LY367385对脑星形胶质细胞Na^+-K^+-ATP酶和Ca^2+-Mg^2+-ATP酶的影响。方法:分离、培养小鼠脑星形胶质细胞,分为谷氨酸组、谷氨酸+LY367385组、谷氨酸+DMSO组和空白对照组,以定磷法检测Na^+-K^+-ATP酶和Ca^2+-Mg^2+-ATP酶活性,以高效液相色谱法测定ATP含量。结果:与空白对照组相比,谷氨酸组、谷氨酸+LY367385组和谷氨酸+DMSO组Na^+-K^+-ATP酶活性、Ca^2+-Mg^2+-ATP酶活性和ATP水平显著降低(P〈0.05);谷氨酸+LY367385组和谷氨酸+DMSO组显著高于谷氨酸组(P〈0.001),两组间则无明显差异。结论:mGluR1选择性拮抗剂LY367385可提高Na^+-K^+-ATP酶和Ca^2+-Mg^2+-ATP酶活性,减少ATP消耗,从而有效保护脑星形胶质细胞,有望成为预防和治疗肝性脑病的药物。
Background: Swelling of brain astrocytes is the characteristic of cerebral edema of liver failure, however, its mechanism has not been fully known yet. Aims: To study the effect of LY367385, a selective antagonist of group I metabotropic glutamate receptor (mGluR1), on activities of Na^+-K^+-ATPase and Ca^2+-Mg^2+-ATPase of brain astrocytes. Methods: Brain astrocytes in mice were isolated and cultured, and then were divided into glutamate group, glutamate+ LY367385 group, glutamate+DMSO group and blank control group. The activities of Na^+-K^+-ATPase and Ca^2+-Mg^2+-ATPase were determined by colorimetric determination of phosphorus. The level of ATP was measured by high performance liquid chromatography. Results: Compared with blank control group, the activities of Na^+-K^+-ATPase, Ca^2+-Mg^2+-ATPase and level of ATP were significantly lower in the other three groups (P〈0.05). All the above-mentioned indexes in glutamate+ LY367385 group and glutamate+DMSO group were significantly higher than those in glutamate group (P〈0.001), but no significant difference was found between the former two groups. Conclusions: Selective antagonist of mGluR1 LY367385 can increase the activities of Na^+-K^+-ATPase and Ca^2+-Mg^2+-ATPase, and decrease the consumption of ATP, thereby can effectively protect the brain astrocytes, and it may become a promising drug for preventing and treating hepatic encephalopathy.
出处
《胃肠病学》
2009年第1期35-38,共4页
Chinese Journal of Gastroenterology
基金
本课题由云南省教育厅基金(06Y181C)、云南省科技厅昆明医学院联合专项基金(2007C0014R)资助