氢自由基水对慢性应激诱导的抑郁样行为的改善作用研究

Study on improvement effect of hydrogen free radical water on depression⁃like behavior induced by chronic unpredictable mild stress

目的:观察氢自由基水的安全性及其对大鼠抑郁样行为的改善效果。方法:将20只雌雄各半的6周龄Sprague-Dawley(SD)大鼠基于体重随机分为实验组和对照组,实验期间分别给予高浓度氢自由基水和等量蒸馏水灌胃,观察并记录各组大鼠的一般情况、体重变化并进行相关病理学检查。将32只雄性4周龄SD大鼠基于体重随机分为正常对照组、模型组、低浓度组、高浓度组,对模型组、低浓度组、高浓度组大鼠进行慢性不可预测轻度应激干预6周,构建慢性不可预测轻度应激大鼠抑郁模型,通过观察各组大鼠行为学指标、血清皮质酮水平评估氢自由基水对抑郁大鼠的影响;通过比较各组大鼠血常规、血生化及病理切片结果初步评价氢自由基水的短期安全性。结果:相同性别时,实验组与对照组同期体重增长率、重要器官脏器指数比较,差异均无统计学意义(均P>0.05)。为期6周的慢性不可预测轻度应激干预大鼠呈现了抑郁样行为,低浓度组、高浓度组能有效缓解;各组血常规结果均在正常范围内;低浓度组、高浓度组碱性磷酸酶水平虽低于正常对照组(均P<0.05),但与模型组比较差异无统计学意义(P>0.05);正常对照组、模型组、低浓度组、高浓度组γ-谷氨酰氨基转移酶、尿素、肌酐、天门冬氨酸氨基转移酶、血清白蛋白比较,差异均无统计学意义(均P>0.05);镜下发现,模型组肾小管上皮细胞变性坏死程度较高浓度组更严重,模型组膀胱黏膜下层局部可见轻微炎症细胞浸润,而高浓度组未见,其余脏器组织高浓度组与正常对照组比较均未见明显异常。结论:在本实验条件下,实验结果未显示出氢自由基水有急性和短期毒性效应及毒作用特征,并发现其对慢性不可预测轻度应激诱导的抑郁样行为有一定保护作用,可能具有剂量效应。

Objective:To observe the safety of hydrogen free radical water and its improvement effect on depression-like behavior in rats.Methods:20 Sprague Dawley(SD)rats of 6 weeks of age in which half was male and half was female were randomly divided into the experimental group and the control group based on body weight.During the experiment,high concentration hydrogen free radical water and equal amount of distilled water were given gavage,respectively.After gavage,the general conditions and body weight changes of the rats in each group were observed and recorded,and related pathological examinations were carried out.32 male SD rats of 4 weeks of age were randomly divided into the normal control group,model group,low concentration group,high concentration group based on body weight.Chronic unpredictable mild stress intervention was carried out for 6 weeks in the model group,low concentration group,high concentration group.Chronic unpredictable mild stress rat depression model was constructed.The effects of hydrogen free radical water on depressed rats was evaluated by observing the behavioral indexes and serum corticosterone.The short-term safety of hydrogen free radical water was preliminarily evaluated by comparing the results of blood routine,blood biochemistry and pathological sections of each group.Results:When the rats were of the same sex,there were no significant differences in the growth rate of body weight at the same time point and organ index of vital organs between experimental group and control group(P>0.05).After 6-week CUMS,rats showed depression-like behavior,which could be effectively alleviated in low concentration group and high concentration group.The blood routine results of each group were within the normal range.Although the level of alkaline phosphatase in low concentration group and high concentration group was lower than that in normal control group(P<0.05),there was no significant difference compared with model group(P>0.05).There were no significant differences in the comparison ofγ-glutamyltransferase,urea,creatinine,aspartate aminotransferase,and serum albumin among normal control group,model group,low concentration group,high concentration group(all P>0.05).Microscopically,it was found that the degeneration and necrosis of renal tubular epithelial cells in the model group was more serious than that in the high concentration group.Minor inflammatory cell infiltration was observed locally in the submucosa of the bladder in the model group,but not in the high concentration group.No significant abnormalities were observed in the other organ tissues in the high concentration group compared with the normal control group.Conclusion:Under the experimental conditions,the results of this study don′t indicate any acute or short-term toxic effects or toxicological profiles of hydrogen free radical water,and suggest that it may have a protective effect against chronic unpredictable mild stress-induced depressive-like behaviors,possibly with a dose-dependent effect.