黄芪注射液对抑郁模型小鼠抑郁行为影响及IL-18与小鼠抑郁行为相关性的对照研究

发布时间：2018-04-27 11:01

本文选题：黄芪注射液 + 白细胞介素-18　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:选取抑郁障碍建模成功的C57BL/6J型号小鼠,按照干预药物的种类和剂量进行分组,比较干预前后小鼠血清及脑内IL-18的水平变化,分析IL-18水平变化与抑郁模型小鼠抑郁行为的相关性;探索脑内及血清IL-18的水平变化方向是否一致;为IL-18能否用于临床抑郁症的诊断、病情判断提供一些基础研究证据。方法:1、按照随机分组的方法,将60只健康清洁级C57BL/6J型号小鼠(购于山西医科大学实验动物中心)按照干预药物及剂量的不同,随机分为6组,每组10只,分别为(1)健康对照组(2)抑郁模型对照组(3)帕罗西汀治疗组(4)黄芪注射液高剂量组(5)黄芪注射液中剂量组(6)黄芪注射液低剂量组。2、干预:帕罗西汀干预组按设计剂量5mg/kg/d进行灌服,黄芪注射液干预组按剂量不同分别采取0.025ml/kg/d、0.050ml/kg/d、0.075ml/kg/d(分别相当于原生药2g/kg/d、4g/kg/d、6g/kg/d)进行腹腔注射,共干预56天。对照组无药物干预,其他处理与干预组相同。在干预前,采取各小鼠血样,抑郁模型组经过56天相应药物干预后,再次采取各组血样,同时断头处死小鼠,摘取小鼠海马组织,经蜡块包埋后做切片。用ELISA法测量小鼠血清IL-18水平,用免疫组化法处理小鼠海马切片,检测小鼠海马组织中IL-18染色细胞数的表达情况。最后,用SPSS 22.0统计软件对数据进行分析。结果:1、抑郁小鼠模型建造结果模型小鼠在造模28 d后,出现蜷缩少动、胆小易惊、毛发变粗糙、无光泽、体质量增加减慢、摄食减少、糖水消耗量降低,建模成功;2、小鼠血清IL-18检测结果(1)干预前,与健康对照组相比,各抑郁模型组小鼠血清IL-18水平明显升高,差别有统计学意义(P0.05);(2)干预后,各组抑郁模型抑郁模型小鼠血清IL-18水平变化不一,帕罗西汀组、黄芪注射液高剂量组和黄芪注射液中剂量组小鼠血清IL-18水平显著降低,差别有统计学意义(P0.05);而生理盐水组、黄芪注射液低剂量组小鼠血清IL-18水平变化不明显,差别无统计学意义(P0.05);3、小鼠海马IL-18免疫组化结果各抑郁模型组小鼠在干预后,海马染色细胞数均高于空白对照组,差别有统计学意义(P0.05),其中帕罗西汀组、黄芪注射液高剂量组和黄芪注射液中剂量组小鼠海马染色细胞数明显低于生理盐水组和黄芪注射液低剂量组,差别有统计学意义(P0.05)。结论:1、小鼠血清IL-18水平变化可能与其抑郁症的发生发展及转归相关。2、各组抑郁模型组小鼠的血清及海马IL-18水平变化方向一直,血清IL-18水平可以间接反映脑内IL-18水平。3、高剂量黄芪注射液和中剂量黄芪注射液均能起到有效的抗抑郁作用,低剂量黄芪注射液抗抑郁作用不明显。
[Abstract]:Objective: to select C57BL/6J model mice with depressive disorder and group them according to the type and dosage of intervention drugs, and compare the changes of IL-18 levels in serum and brain before and after intervention. To analyze the correlation between the level of IL-18 and depressive behavior in depressive model mice, to explore whether the change direction of IL-18 in brain and serum is the same, and to provide some basic research evidence for the diagnosis of clinical depression and the judgement of the condition of IL-18. Methods: according to the method of random grouping, 60 healthy and clean grade C57BL/6J mice (purchased from Experimental Animal Center of Shanxi Medical University) were randomly divided into 6 groups, 10 mice in each group. 1) healthy control group 2) depression model control group 3) paroxetine treatment group 4) Astragalus injection high dose group 5) Astragalus injection middle dose group 0) Astragalus injection low dose group 2, intervention: paroxetine intervention group was administered with designed dose of 5mg/kg/d. In the astragalus injection intervention group, 0.025 ml / kg / d 0.050 ml / kg / d 0.075 ml / kg / d (equivalent to 2 g / kg / d 4 g / kg / d) of 0.025 ml / kg / d 0.050 ml / kg / d 0.075 ml / kg / d, respectively, were injected intraperitoneally for 56 days. There was no drug intervention in the control group, and other treatments were the same as those in the intervention group. Before intervention, each mouse blood sample was taken. After 56 days of intervention, the depressive model group took each blood sample again, at the same time, the mice were killed at the same time, the hippocampal tissue of the mice was removed, and then embedded with wax block to be sliced. The level of serum IL-18 was measured by ELISA method, and the expression of IL-18 staining cells in the hippocampus of mice was detected by immunohistochemical method. Finally, the data are analyzed with SPSS 22. 0 statistical software. Results: 1. After 28 days of modeling, the model mice developed curling, timid, frightened, coarse hair, dull hair, slow body mass, decreased intake, and decreased consumption of sugar and water. Before the intervention, the serum IL-18 level in the depression model group was significantly higher than that in the healthy control group, and the difference was statistically significant (P 0.05). The levels of serum IL-18 were significantly decreased in paroxetine group, high dose group of Astragalus membranaceus injection and middle dose group of Astragalus membranaceus injection, the difference was statistically significant (P 0.05), while that of normal saline group was significantly lower than that of normal saline group. The level of serum IL-18 in the low dose group of Astragalus membranaceus injection did not change significantly, but there was no significant difference between the two groups. The IL-18 immunohistochemical results of mice hippocampus showed that the number of stained cells in hippocampus of the depression model group was higher than that of the blank control group after intervention. The number of stained cells in hippocampus of paroxetine group, high dose group of astragalus injection and middle dose group of Astragalus membranaceus injection was significantly lower than that of normal saline group and low dose group of astragalus injection, and the difference was statistically significant (P 0.05). Conclusion the changes of serum IL-18 level in mice may be related to the occurrence, development and outcome of depression. The changes of serum and hippocampal IL-18 levels in the depression model group are always in the same direction. The level of serum IL-18 can indirectly reflect the level of IL-18 in brain. High dose Astragalus injection and medium dose Astragalus injection can play an effective antidepressant effect, low dose Astragalus injection has no obvious antidepressant effect.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.4;R-332

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