高压氧对慢性应激抑郁模型大鼠行为及神经干细胞移植的影响

Effects of hyperbaric oxygen on behavior and transplanted neural stem cells in rats with chronic stress depression

背景:高压氧治疗缺血缺氧性疾病的效果已得到公认,但需要与其他手段进行联合治疗。目的:观察高压氧联合神经干细胞移植治疗大鼠慢性应激抑郁的效果。方法:将60只SD大鼠随机分为4组,正常组不进行任何处理;神经干细胞组、联合组、模型组建立慢性应激抑郁模型。造模成功后24 h,联合组尾静脉注射神经干细胞悬液1 mL(细胞数3×106),同时给予高压氧治疗,4次/d,持续1周;神经干细胞组尾静脉注射神经干细胞悬液1 mL(细胞数3×106)。造模成功后72 h,TUNEL法测定神经细胞凋亡情况;治疗后2周,观察神经干细胞的存活和分布情况,尼氏染色法检测大鼠海马神经元形态;治疗后1,2周,进行体质量测量、蔗糖水消耗实验;治疗后5 min内进行旷场实验,观察大鼠行为学改变。结果与结论:(1)与正常组比较,模型组大鼠体质量、蔗糖水消耗量、矿场实验垂直直立次数与水平运动距离明显减少(P<0.05),神经细胞凋亡数量明显增加(P<0.05);(2)与模型组比较,神经干细胞组、联合组大鼠体质量、蔗糖水消耗量、矿场实验垂直直立次数与水平运动距离明显升高(P<0.05),神经细胞凋亡数量明显减少(P<0.05),联合组的效果优于神经干细胞组(P<0.05);(3)联合组移植神经干细胞存活数量明显多于神经干细胞组(P<0.05);(4)模型组神经元数目相对较少,结构不完整;神经干细胞组及联合组神经元数目多,结构完整;联合组神经元数目较神经干细胞组多,但少于正常组;(5)结果表明,神经干细胞联合高压氧可改善慢性应激抑郁模型大鼠的抑郁行为及海马神经元凋亡情况。

BACKGROUND：Hyperbaric oxygen as a wel-recognized therapy for ischemic and hypoxic diseases has to be combined with other treatments. OBJECTIVE：To study the effects of hyperbaric oxygen combined with neural stem cel transplantation via tail vein in chronic stress depression rats. METHODS：Of 60 Sprague-Dawley rats, 15 rats randomly selected were given no treatment as normal group, and the rest 45 ones were used to establish a rat model of depression and randomly divided into three groups：model group （n=15, without giving any treatment）, neural stem cel group （n=15, injection of 1 mL neural stem cel suspension （3×10^6） via the tail vein） and combined group （n=15, hyperbaric oxygen treatment plus neural stem cel injection）. Hyperbaric oxygen treatments were carried out four times per day, for 1 week, and al the treatments were given 24 hours after modeling. Rats in each group were subjected to body mass measurement and sugar water consumption test 1 and 2 weeks after treatment, and open field test within 5 minutes after treatment to observe rat behavior changes. The survival and distribution of CM-Dil labeled neural stem cel s were observed by fluorescence microscopy. The changes in the size, morphology and number of hippocampus neurons in rat were detected by the method of nylon staining. TUNEL method was used to measure the apoptosis of nerve cel s. RESULTS AND CONCLUSION：Compared with the normal group, in the model group, rat’s body weight, sucrose water preference and open field test scores were significantly lower, reduced number of hippocampal neurons with intact structure was found and TUNEL results showed more apoptosis （P〈0.05）. Compared with the model group, the body weight, sucrose preference and open field test score increased significantly （P〈0.05）, the number of hippocampal neurons was increased, while the number of apoptotic cel s was reduced significantly in the neural stem cel and combined groups （P〈0.05）. Compared with the neural stem cel group, these indexes were improved more significantly in the combined group （P〈0.05）. More CM-Dil positive cel s were found in the combined group than the neural stem cel group （P〈0.05）. Additional y, the number of hippocampal neurons was higher in the combined group than the neural stem cel group, but lower than the normal group. To conclude, transplantation of neural stem cel s combined with hyperbaric oxygen can improve the depression behavior and apoptosis in the hippocampal neurons in chronic stress depression rats.