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...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。展开更多
Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of...Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion （DRG） neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200--260 g were anesthetized with the intraperitoneal injection of 300 mg· kg^-1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4--0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2--4. The animals were decapitated 14 days after the surgery. The L4--L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group （P〈0.01）, and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.展开更多
文摘研究槲皮素(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。
文摘Neuropathic pain has been hypothesized to be the result of aberrant expression and function of sodium channels at the site of injury. To investigate the effects of NaV1.8 antisense oligonucleotide on the expression of sodium channel mRNA in dorsal root ganglion （DRG） neurons in chronic neuropathic pain. 24 Sprague-Dawley rats weighing 200--260 g were anesthetized with the intraperitoneal injection of 300 mg· kg^-1 choral hydrate. The CCI model was made by loose ligation of sciatic nerve trunk by 4--0 chromic gut. The mechanical and thermal pain threshold were measured before operation and 1, 3, 5, 7, 9, 11, 13 days after operation. A PE-10 catheter was implanted in subarachnoid space at lumbar region. On the 7th postoperative day the animals were randomly divided into 4 groups. The drugs were injected intrathecally twice a day for 5 consecutive days in group 2--4. The animals were decapitated 14 days after the surgery. The L4--L6 DRG of the operated side was removed and crushed, and total RNA was extracted with Trizol reagent. The contralateral side was used as control. The change of NaV1.8 sodium channel transcripts was determined by RT-PCR. Pain threshold was significantly lowered after CCI as compared with that in control group and was elevated 3 days after antisense oligonucleotide injection. Sensory neuron specific TTX-R sodium channel NaV1.8 transcript was down-regulated after antisense oligonucleotide injection at the dosage of 45 μg as compared with that in CCI group （P〈0.01）, and it was even greater at the dosage of 90 μg. The intrathecally injected NaV1.8 antisense oligonucleotide can reduce the mechanical allodynia and thermal hyperalgesia partially by downregulating the SNS transcript expression.
