环氧合酶-2介导四氢大麻酚抑制CA1区长时程抑制的作用

COX-2 modulates △^9-THC-induced inhibition of LTD in CA1 area

目的探讨环氧合酶-2（cyclooxgense-2，COX-2）在四氢大麻酚（△^9-tetrahydrocannabin01，△^9-THC）抑制CA1区长时程抑制（long—term depression，LTD）中的作用。方珐在小鼠腹腔注射△^9-THC（10mg／kg）或COX-2的选择性抑制剂NS398（10mg／kg）24h后切片，在海马CA1区记录场电位EPSP（fEPSP），观察NS398和△^9-THC在LTD中的作用，并结合全细胞膜片钳技术观察THC对神经元膜兴奋性的影响。结果①给予低频电刺激（1Hz，15min）诱导CA1区LTD，△^9-THC可显著降低LTD。②△^9-THC并不改变海马CAl区基本的突触传递和膜的基本电学特性（包括膜电位、输入阻抗及放电特性）。③△^9-THC显著降低LTD的效应可被COX-2的选择性抑制剂NS398所反转。④在COX-2基因敲除的小鼠，△^9-THC降低LTD的作用被显著抑制。结论在CA1区COX-2介导了△^9-THC降低LTD的作用。

Objective To explore the role of cyclooxgense-2 （COX-2） in tetrahydrocannabinol （THC）- induced inhibition of long-term depression （LTD） in CA1 area in vitro. Methods The hippocampal s/ices were prepared at 24 h after intraperitoneal injection of △^9-THC （10 mg/kg） or COX-2 inhibitor NS398 （10 mg/kg）. Field excitatory post-synaptic potentials （fEPSP） were recorded in the stratum radiatum of the CA1 area in vitro to observe the effect of NS398, a selective inhibitor of COX-2, on the THC-induced inhibition of LTD and THC＇s effect on membrane excitability in pyramidal neurons by using the whole-cell patch clamp technique. Results ① Low-frequency stimulation （1 Hz, 15 min） induced-LTD in CA1 area was significantly attenuated by △^9-THC. ② ALTHC did not affect the basal synaptic transmission and membrane excitability （including membrane resting potentials, input resistance and firing property）. ③ THC-induced inhibition of LTD was reversed by NS398. ④ THC-induced inhibition of LTD was robustly impaired in COX-2 knockout mice. Conclusion THC-induced inhibition of LTD in CA1 area was mediated via COX-2.