高压氧联合中药冰片对大鼠血脑屏障丙戊酸钠透过率的影响

The combined effect of hyperbaric oxygen and borneol on the permeability of the blood-brain barrier to sodi-um valproate

目的 观察高压氧（HBO）联合中药冰片对大鼠血脑屏障（BBB）丙戊酸钠透过率的影响.方法 选取56只健康SD大鼠,按照随机数字表法将其分为对照组（腹腔注射丙戊酸钠0.1 g/kg）、HBO-1组（HBO治疗结束后0.5h注射丙戊酸钠0.1 g/kg）、HBO-2组（HBO治疗同时注射丙戊酸钠0.1 g/kg）、HBO-3组（HBO治疗前0.5h注射丙戊酸钠0.1 g/kg）、低剂量冰片组（灌服0.125 g/kg冰片0.5h后注射丙戊酸钠0.1 g/kg）、高剂量冰片组（灌服0.25 g/kg冰片0.5h后注射丙戊酸钠0.1 g/kg）、联合应用组（灌服0.125 g/kg冰片0.5h后注射丙戊酸钠0.1 g/kg,0.5h后进行HBO治疗）,每组8只.注射丙戊酸钠1.5h后,取大鼠的血液及脑脊液,采用高效液相色谱法测定丙戊酸钠的浓度.结果 与对照组比较,HBO-2组[（97.43 ±12.09）mg/L]、HBO-3组[（100.10±13.54） mg/L]大鼠脑脊液丙戊酸钠浓度均显著增加,差异有统计学意义（P＜0.05）,脑脊液血浆浓度比也明显增高（P＜0.05）;与对照组比较,高剂量冰片组大鼠脑脊液丙戊酸钠浓度[（91.09±9.45）mg/L]及脑脊液血浆浓度比值（0.577±0.051）较高,差异有统计学意义（P＜0.05）.与低剂量冰片组比较,HBO-3组、联合应用组大鼠脑脊液丙戊酸钠浓度较高,差异有统计学意义（P＜0.05）.与HBO-3组比较,联合应用组大鼠脑脊液丙戊酸钠浓度[（112.43±11.52）mg/L]及脑脊液血浆浓度比（0.698±0.058）均显著增加（P＜0.05）.各组间血液丙戊酸钠浓度比较,差异均无统计学意义（P＞0.05）.结论 HBO疗法可提高大鼠BBB对丙戊酸钠的通透性,与低剂量冰片联用后效果更佳.

Objective To observe the effect of hyperbaric oxygen （HBO） combined with borneol on the permeability of the blood-brain barrier to sodium valproate in rats.Methods Fifty-six male,healthy Sprague Dawley rats were randomly divided into a control group which received an intraperitoneal injection of sodium valproate （0.1 g/kg）,an HBO-1 group to which HBO was administered 0.5 hours before an equivalent injection of sodium valproate,an HBO-2 group where the HBO and sodium valproate were administered together,an HBO-3 group which received HBO 0.5 hours after the injection,a low dosage borneol group （L-borneol） which received 0.125 g/kg of borneol by oral perfusion 0.5 hours before an injection of sodium valproate （0.1 g/kg）,a high dosage borneol group which received 0.25 g/kg of borneol 0.5 hours before an injection of sodium valproate （0.1 g/kg） and a combined group which received the HBO-3 group＇s treatment supplemented with the borneol dose of the L-borneol group.There were 8 rats in each group.Blood and cerebrospinal fluid （CSF） were collected 1.5 h after the sodium valproate injection and the concentrations of sodium valproate were measured by high performance liquid chromatography.Results Compared with the control group,the CSF concentrations of sodium valproate in the HBO-2 and HBO-3 groups had increased significantly more （to 97.43 ± 12.09 mg/L and 100.10 ± 13.54 mg/L respectively）.The ratios of the CSF to plasma （C/P） concentrations had also increased significantly more.The CSF concentration of sodium valproate in the H-borneol group （91.09 ± 9.45 mg/L） and the C/P ratio （0.577 ± 0.051） had increased significantly more than in the control group.Compared with the L-borneol group,there were significantly greater increases in the HBO-3 group and the combined group in the concentration of sodium valproate in the rats＇ CSF.Compared with the HBO-3 group,the average concentration of sodium valproate in the CSF of the combined group （112.43 ± 11.52 mg/L） and the C/P ratio （0.698 ±0.058） had increased significantly more.There was no significant difference among the groups in the plasma concentrations of sodium valproate.Conclusions HBO can increase the permeability of the blood-brain barrier to sodium valproate,at least in rats.Combining HBO with a low dose of borneol has an additional effect.