槲皮素对大鼠DRG神经元Nav1.8电流的作用及机制

研究槲皮素（Que）对大鼠脊髓背根神经节（DRG）神经元Nav1.8通道电流（INav1.8）的作用。在急性分离的大鼠DRG神经元上,用全细胞膜片钳技术,观察Que干预INav1.8的剂量-反应关系以及Que影响的Nav1.8通道电压依赖的激活和失活特性。结果显示Que（10,30,100μmol/L）可浓度依赖地抑制DRG神经元INav1.8峰值,峰值抑制率分别为（15.32±3.43）%,（22.92±8.24）%和（47.29±11.42）%,半数抑制浓度（IC50）为121.38μmol/L,Hill系数为0.76;100μmol/L Que可使DRG神经元的Nav1.8通道激活曲线向去极化方向偏移了0.83 m V,失活曲线向超极化方向偏移了1.86 m V;且与干预前比,半数失活电压（V1/2）为-（40.23±0.25）m V,有显著性差异（P＜0.01）。说明Que可浓度依赖和电压依赖地抑制DRG神经元Nav1.8通道活性,进而降低痛觉信息的传递,改善慢性内脏痛。

To study the effects of quercetin (Que) on the electric current of Nav1.8 (I_Nav1.8) in rat dorsal root ganglion (DRG) neurons, dose-effect relationship of Que on I_Nav1.8 and the activation and inactivation properties of voltage-dependent Nav1.8 influenced by Que were studied by using the whole-cell patch clamp technique in fresh isolated rat DRG neurons. It was found that diffeent concerntrations of Que (10, 30, 100 μmol/L) could inhibit I_Nav1.8 peak value of DRG neurons in concentration-dependent manner. The inhibition of peak currents were (15.32 ± 3.43)%, (22.92 ± 8.24)% and (47.29 + 11.42)% respectively, the IC₅₀ was 121.38 μmol/L and the Hill coefficient was 0.76. In the existence of Que (100 μmol/L), the activation curve of Nav1.8 channel in DRG was slightly shifted to depolarizing direction for 0.83 mV, and the inactivation curve was shifted to hyperpolarizing direction for 1.86 mV. Compared with the stage before intervention, the half-activation voltage (V_1/2 = -40.23 ± 0.25 mV) was significantly different (P < 0.01). In conclusion, Que inhibits the Navl. 8 channel activity in dose and voltage-dependent manner, which may count for the reduction of algesthesia transmission and the alleviation of chronic visceral pain.