外源性硫化氢在改善慢性应激引起大鼠抑郁作用的研究

Effects of exogenous hydrogen sulfide on the depression rat model caused by chronic stress

目的:探讨外源性硫化氢供体NaH S对慢性应激致大鼠抑郁模型的影响,为抑郁症的防治提供新思路。方法:SD大鼠按随机数字表法分为4组:正常对照组、模型组、模型+NaH S组、模型+NS组,每组6只。模型+NaH S组和模型+NS组大鼠在建模前分别给予NaH S 10 mg/kg或等量生理盐水腹腔注射。记录各组大鼠的体重、食量、饮水量、糖水偏好率、肾上腺指数及行为学指标,并收集大鼠海马组织,采用Real-Time PCR和Western Blot分别检测海马组织糖皮质激素受体和盐皮质激素受体基因mRNA及蛋白表达量。结果:模型组大鼠的体重、食量、饮水量、糖水偏好率、水平运动格数及垂直竖立次数较正常对照组均明显降低(P<0.05),而肾上腺指数在模型组显著高于正常对照组(P<0.05);NaH S处理的模型组大鼠体重、食量、饮水量、糖水偏好率、水平运动格数及垂直竖立次数均明显增加,且肾上腺指数显著降低,与模型组相比差异有统计学意义(均P<0.05)。Real-Time PCR和Western Blot结果显示:海马组织中糖皮质激素受体和盐皮质激素受体基因mRNA及蛋白表达量在模型组均明显低于正常对照组,模型+NaH S组均显著高于模型组,两组相比差异有统计学意义(均P<0.05)。结论:慢性应激可引起大鼠抑郁表现,而外源性硫化氢供体NaH S能够显著上调糖皮质激素受体和盐皮质激素受体表达水平,从而改善慢性应激所致的大鼠抑郁。

Objective： To explore the effects of exogenous hydrogen sulfide（ H2S） donor NaH S on the depression rat model induced by chronic stress,and provide a new idea for preventing and treating depression. Methods： Sprague Dawley rats were divided into four groups according to random number table method： normal control group,model group,model ＋ NaH S group and model ＋ normal saline group with 6 rats in each group. Model ＋ NaH S and model ＋ normal saline group were administered by intraperitoneal injection with NaH S（ 10 mg / kg） or equivalent normal saline before modeling,respectively. The weight,food intake,water intake,sugar water preference,adrenal gland weight index and behavioral indexes were observed in these rats,and their hippocampal tissues were collected. The mRNA and protein expression of mineralocorticoid receptor（ MR） and glucocorticoid receptor（ GR） in the hippocampus were assayed by Real-Time PCR or Western Blot,respectively. Results： The weight,food intake,water intake,sugar waterpreference,the number of horizontal movement and vertical erect of rats were lower in model group than that in normal control group（ P 0. 05）. In model group rats,adrenal gland weight index was increased significantly compared with normal control group（ P 0. 05）,but the indexes above mentioned were improved significantly in model group rats treated with NaH S（ P 0. 05）. The results of Real-Time PCR and Western Blot showed that the mRNA and protein expression of GR and MR in hippocampal tissues of rats were decreased greatly in model group compared with normal control group（ P 0. 05）,but were significantly improved in model ＋ NaH S group compared with model group（ P 0. 05）.Conclusion： Chronic stress could lead to depression of rats,and exogenous H2 S donor NaH S could attenuate chronic stress induced-depression of rats by upregulating the expression of GR and MR in hippocampal tissues of rats.