II、III组亲代谢型谷氨酸受体激动剂对脂多糖抑制C6胶质瘤细胞摄取谷氨酸的影响

Agonists of group II and III metabotropic glutamate receptors reverse LPS-induced glutamate uptake inhibition in C6 glioma cells

目的:探讨II、III组亲代谢型谷氨酸受体(metabotropic glutamate receptors,mGluRs)激动剂对脂多糖(LPS)抑制C6胶质瘤细胞摄取谷氨酸(gluta-mate,Glu)的影响。方法:应用同位素标记法测定C6胶质瘤细胞对[3H]-D,L-Glu的摄取。应用Ho-echst染色法、噻唑蓝比色法(MTT)分别检测C6胶质瘤细胞的凋亡、细胞活力。结果:LPS(4、6μg/mL)显著抑制C6胶质瘤细胞摄取[3H]-D,L-Glu,抑制率分别达17.6%和22.2%。II组mGluRs激动剂DCG-IV100μmol/L和III组mGluRs激动剂L-AP4100μmol/L逆转LPS对C6胶质瘤细胞摄取[3H]-D,L-Glu的抑制作用,这种逆转作用分别被II、III组mGluRs拮抗剂APICA和MSOP取消。结论:DCG-IV和L-AP4逆转LPS引起的C6胶质瘤细胞Glu摄取抑制,提示II、III组mGluRs激动剂通过促进Glu摄取,降低细胞外Glu浓度,从而发挥神经保护作用。

To study whether agonists of group Ⅱ and Ⅲ metabotropic glutamate receptors （mGluRs） exert effects on LPS-induced glutamate uptake inhibition in C6 glioma cells. METHODS： The glutamate uptake into C6 glioma cells was measured by uptake of [^3H]-D,Lglutamate; and the apoptosis and the viability of C6 glioma cells were investigated by Hoechst33342 and MTT methods, respectively. RESULTS： LPS （4, 6 μg/mL） inhibited glutamate uptake significantly compared with that in the control group without effect on the apoptosis and viability of C6 glioma cells. Pretreatment of C6 glioma cells with group II and m mGluRs agonists DCG-IV（1130/μml/L） and L-AP4（1130 μmol/L） reversed LPS-induced glutamate uptake inhibition. These recovery effects were abolished by their respective antagonists APICA and MSOP. CONCLUSION： Activation of group II and Ⅲ mGluRs recovers LPS-induced glutamate uptake inhibition in C6 glioma cells, suggesting the enhancement of glutamate uptake is involved in neuroprotective roles exerted by group Ⅱ and Ⅲ mGluRs agonists.