利培酮对抑郁症大鼠海马区神经元细胞损伤和免疫紊乱的调节  

Regulation of risperidone for hippocampal neuron damage and immune disorder in depression rats

作　　者：谢莲萍 赵玉梅 陈丽萍 王崇 国树梅 XIE Lian-ping;ZHAO Yu-mei;CHEN Li-ping;WANG Chong;GUO Shu-mei(Department of Pharmacy,Seventh People’s Hospital of Hengshui,Hengshui Hebei 053000,China;Department of Pharmacy,Hongqi Hospital Affiliated to Mudanjiang Medical College,Mudanjiang Heilongjiang 157000,China)

机构地区：[1]衡水市第七人民医院药剂科,河北衡水053000 [2]牡丹江医学院附属红旗医院药剂科,黑龙江牡丹江157000

出　　处：《局解手术学杂志》2023年第1期15-21,共7页Journal of Regional Anatomy and Operative Surgery

基　　金：黑龙江省自然科学基金(UNPYSCT-2018171)。

摘　　要：目的 探讨利培酮对抑郁症大鼠海马区神经元细胞损伤和免疫紊乱的影响。方法 将100只SD大鼠分为对照组、模型组、利培酮低剂量组、利培酮中剂量组、利培酮高剂量组,除对照组外,其余各组均运用慢性不可预见应激(CUS)法制备抑郁症大鼠模型,于实验进行第22天分别给予利培酮低剂量组、利培酮中剂量组、利培酮高剂量组0.05 mg/kg、0.10 mg/kg、0.20 mg/kg利培酮腹腔注射干预,模型组和对照组注射相应体积生理盐水,每天1次,连续14 d。比较各组大鼠神经功能损伤评分、跳台实验犯错误次数、神经递质水平。Western blot检测海马区谷氨酸转运体(GLT-1)、脑源性神经营养因子(BDNF)和凋亡相关蛋白水平。ELISA检测外周血和脑组织中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)水平。HE染色和尼氏小体染色分别观察海马区病理变化和尼氏小体情况。结果 与对照组相比,模型组大鼠跳台实验犯错误次数、神经功能损伤评分、外周血和脑组织中IL-6、TNF-α、IL-10水平和Caspase-9、Caspase-3、Bcl-2/Bax蛋白水平显著增加/升高(P<0.05),5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)水平和GLT-1、BDNF蛋白水平显著降低(P<0.05);与模型组相比,利培酮中剂量组、利培酮高剂量组跳台实验犯错误次数、神经功能损伤评分、外周血和脑组织中IL-6、TNF-α水平和Caspase-9、Caspase-3、Bcl-2/Bax蛋白水平显著减少/降低(P<0.05),5-HT、5-HIAA水平和GLT-1、BDNF蛋白水平及外周血和脑组织中IL-10水平显著升高(P<0.05)。HE染色结果显示,模型组、利培酮低剂量组大鼠的海马区神经元细胞表现为核固缩、胞质浓缩、细胞排列杂乱无章,而利培酮中剂量组、利培酮高剂量组海马区神经元细胞排列较紧密有序,损伤程度减轻。尼氏小体染色结果显示,模型组、利培酮低剂量组大鼠海马区尼氏小体颗粒减少,细胞形态发生改Objective To explore the effects of risperidone on hippocampal neuron damage and immune disorder in depression rats.Methods A total of 100 SD rats were divided into the control group, the model group, the low-dose risperidone group, the middle-dose risperidone group and the high-dose risperidone group. Except for the control group, depression rat models were prepared by chronic unpredictable stress(CUS) method in the other groups. On the 22nd day of the experiment, the low-dose risperidone group, the middle-dose risperidone group and the high-dose risperidone group were given intraperitoneal injection of risperidone(0.05 mg/kg, 0.10 mg/kg, 0.20 mg/kg),while the model group and the control group were given the corresponding volume of normal saline, once a day, for 14 consecutive days. The neurological impairment score, times of mistakes in step-down test and levels of neurotransmitters of rats were compared among all groups. The levels of glutamate transporter-1(GLT-1),brain-derived neurotrophic factor(BDNF) and apoptosis-related proteins in the hippocampus were detected by Western blot. The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in peripheral blood and brain tissue were detected by ELISA. The pathological changes in the hippocampus and Nissl body condition were observed by HE staining and Nissl body staining.Results Compared with the control group, times of mistakes in step-down test, neurological impairment score, levels of IL-6,TNF-α and IL-10 in peripheral blood and brain tissue, and expression levels of Caspase-9,Caspase-3 and Bcl-2/Bax proteins were significantly increased in the model group(P<0.05),while the levels of 5-hydroxytryptamine(5-HT),5-hydroxyindoleacetic acid(5-HIAA),and expression levels of GLT-1 and BDNF proteins were significantly decreased(P<0.05). Compared with the model group, times of mistakes in step-down test, neurological impairment score, levels of IL-6 and TNF-α in peripheral blood and brain tissue, and expression levels of Caspase-9

关 键 词：抑郁症 利培酮 神经元损伤 免疫紊乱 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]