高压氧治疗后血管性痴呆大鼠海马区神经发生及血液供应的变化

Effects of hyperbaric oxygen on neurogenesis and blood-supply in hippocampus of rats with vascular dementia

目的探讨血管性痴呆(VD)大鼠接受高压氧治疗后海马区神经发生及血液供应情况。方法实验设正常组、VD组、高压氧治疗(HBO)组,每组10只。40只大鼠进行VD造模,造模术后30d,选择大鼠20只随机均分为VD组和HBO组。其中,HBO组接受10d的高压氧治疗。CT灌注成像技术检测大鼠海马区局部脑血流量(rCBF)、局部脑血容量(rCBV)和平均通过时间(MTT);穿梭箱系统检测大鼠学习记忆功能,以主动回避反应(AAR)比率(完成AAR的次数/测试总次数)衡量;免疫组化检测海马齿状回(DG)巢蛋白(nestin)和微管相关蛋白doublecortin(DCX)的表达情况。结果与正常组和HBO组比较,VD组海马区rCBV和rCBF下降,MTT延长(P<0.01)。正常组DG区颗粒下层弥漫分布较多nestin阳性细胞,其数目(131.98±13.24个)显著低于VD组(160.46±17.38个,P<0.01)和HBO组(167.82±15.49个,P<0.01)。DCX阳性细胞主要位于紧贴颗粒细胞层下的颗粒下区,VD组DCX阳性细胞(66.27±9.22个)显著低于正常组(123.74±16.90个,P<0.01)和HBO组(155.13±18.28个,P<0.01)。HBO组穿梭箱AAR比率(49.5%±9.3%)较VD组(27.5%±7.9%)显著增加(P<0.01),后者的AAR比率又较正常组(87.5%±7.9%)显著降低(P<0.01)。结论高压氧治疗能够改善VD大鼠认知功能障碍并促进海马区神经发生,其作用机制可能与高压氧治疗提高VD大鼠海马区血液供应有关。

Objective To explore the changes in neurogenesis and blood-supply in the hippocampal dentate gyms （DG） of rats with vascular dementia （VD） after hyperbaric oxygen treatment. Methods Twenty rats with VD were randomized into two groups （10 each） 30 days after reproduction of the model： VD group and hyperbaric oxygen treatment group （HBO）, and 10 normal rats were selected as control （NC）. Rats in HBO group received hyperbaric oxygen therapy for 10 days. CT penfusion imaging was employed to examine the regional cerebral blood flow （rCBF）, regional cerebral blood volume （rCBV） and mean transit time （MTT） in the hippocampus. The ability of learning acquisition and memory were examined with shuttle-box, and assessed by active avoidance response （AAR） ratio （ARR times/exam times）. The expressions of nestin and doublecortin （DCX） in hippocampal DG were detected by immunohistochemistry. Results The rCBF and rCBV declined significantly, while MTT was prolonged in DG of rats in VD group compared with those rats in the other 2 groups （P〈0. 01）. The number of nestin positive cells diffusely existed in the DG of rats in NC group （131. 98±13. 24） were less than that in both VD group （160. 46±17. 38, P〈0. 01） and HBO group （167. 82± 15.49, P〈0. 01）. The number of DCX positive cells, mainly existed in the dentate subgranular zone, were remarkably less in the VD group （66. 27!9.22） than that in both NC group （123. 74 ＋16. 90, P〈0. 01） and HBO group （155. 13＋18. 28, P〈0. 01）. The AAR ratio of HBO group （49. 5%±9. 3%） was significantly higher than that of VD group （27. 5%±7. 9%, P〈0. 01）, and the AAR ratio of VD group was also lower than that of NC group （87. 5%±7. 9%, P〈0. 01）. Conclusion Hyperbatric oxygen therapy may ameliorate the ability of learning and memory and promote neurogenesis in DG of rats with VD, and it may be attributable to the enhanced blood-supply induced by hyperbaric oxygen therapy.