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

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。

Effect of LY367385, a Selective Antagonist of mGluR1, on Na+-K+-ATPase and Ca2+-Mg2+-ATPase of Brain Astrocytes

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.