四逆散对早期慢性应激不同性别大鼠海马星形胶质细胞胶质纤维酸性蛋白的影响

Effects of Sini Powder on hippocampal astrocytes of different sexual rats suffering from chronic unpredictable mild stress in early lifetime

目的:探讨四逆散对早期慢性应激不同性别大鼠海马星形胶质细胞及神经元的干预作用。方法:88只Wistar大鼠雌雄各半,随机分为空白组16只不接受应激,应激组72只接受为期21d的慢性不可预见性应激(CUMS)法应激,然后应激组再次随机分为模型组、四逆散低剂量组、四逆散高剂量组、氟西汀组,继续予以CUMS法应激,同时各给药组给予相应药物水溶液灌胃,空白组和模型组予0.9%氯化钠溶液灌胃,持续21d。末次给药后对各组大鼠检测体质量、糖水偏好率,使用HE染色法观察各组大鼠海马DG区神经元形态,Western blot技术检测海马GFAP表达量。结果:应激各组大鼠体质量显著低于空白组(P<0.05)。各组大鼠糖水偏好率比较均无显著差异。雄鼠各组海马DG区HE染色结果无明显差异,模型组海马GFAP表达量较空白组出现下调趋势,各用药组与模型组比较,GFAP无差异趋势,而雌鼠HE染色显示模型组神经元数量减少、排列疏松,模型组GFAP呈上调趋势,四逆散低剂量组和氟西汀组均能显著降低GFAP表达(P<0.05),改善神经元形态学表现。结论:早期慢性应激可引起海马星形胶质细胞的改变,四逆散能使应激雌鼠海马GFAP恢复至正常水平,改善神经元损伤,为四逆散抗应激损伤早期临床应用提供实验依据。

Objective: To discuss the influence of Sini Powder on hippocampal astrocytes and neurons of different sexual rats suffering from chronic unpredictable mild stress in early lifetime. Methods: Eighty-eight Wistar rats(half male and female) were randomly divided into blank group(16 rats) without chronic unpredictable mild stress in early lifetime and stress group(72 rats) to suffer from the stress for 21 days. Then the stress group was randomly divided again into the model group, the lower dosage of Sini Powder group, the higher dosage of Sini Powder group, and the fluoxetine group, which continued being stressed for another 21 days. Meanwhile the 3 medicated groups were given aqueous solution of the corresponding drug by gavage once a day and the blank controlled group and the model group were given saline. After the last administration, all the rats were weighed, their sucrose preference were tested, the hippocampal DG subregion were observed by HE staining, and the expression of GFAP in their hippocampus were detected by Western blot. Results: The weight of rats in all the groups having been stressed were changed significantly compared respectively with the blank controlled group(P<0.05). All groups did not differ significantly from each other in sucrose preference rate. In HE staining of the hippocampal tissue section, all the male groups were not significantly different from each other in DG; while the female neurons decreased and loosely arranged, but Sini Powder and fluoxetine could treat this pathology. The GFAP in the hippocampus of the male model group was lower than that of the male blank controlled, but the female model group was higher. The GFAP of 3 male medicated groups had no significant difference respectively from that of the male model group. However, in female rats, the GFAP of both the lower dosage of Sini Powder group and the fluoxetine group decreased significantly compared with the model group(P<0.05). Conclusion: Chronic unpredictable mild stress in early lifetime could induce changes in rats' hippocampal astrocytes. But Sini Powder is able to revert the GFAP and treat neuronal insults in female hippocampus after the early stress back to normal level, which could provide experimental evidence for Sini Powder used in treating the early stage of chronic stress damage.