异常黑胆质成熟剂对慢性应激性抑郁大鼠海马FGF2和VEGF表达的影响

The effect of abnormal savda munziq(ASMq) on hippocampal FGF2 and VEGF in animal model of CUMS

目的探讨异常黑胆质成熟剂(ASMq)对慢性应激抑郁大鼠海马中的成纤维细胞生长因子-2(FGF2)和血管内皮生长因子(VEGF)表达的影响。方法选取60只清洁级SD雄性大鼠,体质量180~200g,对其给予21d的不可预知慢性应激(CUMS)建立抑郁模型,通过敞箱实验、糖水消耗实验以及体质量的变化检测CUMS抑郁模型是否成功建立。随后将CUMS抑郁模型大鼠随机分为5组(每组12只):模型对照组(生理盐水,1.5 mL/100g体质量)、阳性对照组(盐酸氟西汀,3.5mg/kg体质量)、ASMq高剂量组(1.5g/kg体质量)、ASMq中剂量组(3.0g/kg体质量)、ASMq低剂量组(6.0g/kg体质量),每日灌胃给药1次,连续给药21d,另设清洁级SD雄性大鼠12只作为正常对照组,不给予任何处理。第21天灌胃1h后苯巴比妥麻醉处死,冰上分离海马,采用蛋白印迹法(Westren blot)和实时荧光定量PCR反应(RT-PCR)分别检测CUMS抑郁模型大鼠海马中的成纤维细胞生长因子-2(FGF2)、血管内皮生长因子(VEGF)蛋白表达量与FGF2、VEGFmRNA的表达量。结果与正常对照组比较,CUMS抑郁模型大鼠体质量减轻,糖水消耗量减少,水平运动和垂直运动得分降低,差异均有统计学意义(P<0.05),CUMS抑郁大鼠模型建立成功。ASMq高、中、低剂量组及阳性对照组大鼠给药后的体质量增长明显高于模型对照组,差异有统计学意义(P<0.05);与正常对照组比较,模型对照组大鼠海马FGF2、VEGF蛋白表达量与FGF2、VEGFmRNA的表达量均下降,差异有统计学意义(P<0.05)。与模型对照组比较,ASMq高、中、低剂量组及阳性对照组大鼠海马FGF2、VEGF蛋白表达量与FGF2、VEGFmRNA的表达量均增加,差异有统计学意义(P<0.05)。结论 ASMq可能是通过提高CUMS抑郁模型大鼠海马中的FGF2和VEGF的表达量,发挥抗抑郁作用。

Objective To observe The effect of ASMq on Hippocampal FGF2 and VEGF in animal model of CUMS. Methods Depression model was established on 60 clean SD male rats, ranging from 180--200 g. Using 21 days of chronic unpredictable mild stress （CUMs）, the behavioral status of rats was evaluated by Open-field test and sugar consumption experiment to affirm whether the depression model is successfully established. Afterwards, the stress animals were randomly divided into 5 group, 12 in each： depression model group（NS,1.5 mL/100 g）, high , middle and low dose group of ASMq （1.5, 3.0, 6.0 g/kg）and positive control group （fluoxetine, 3.5 mg/kg）. The positive control group and the ASMq groups were intragastricadministrated once a day for 21 days. Another 12 SD rats were regard as normal control group （Not accept stress）. At the 21th day, in lh after the last administration, all the rats were executed by phe- nobarbital anesthesia and the hippocampal tissue were separated. Using western blotting and RT-PCR, the expressive levels of FGF2 and VEGF were tested. Results Compared with normal group, in depression group, the body weight, sugar consumption, horizontal crossing numbers and erection times significantly decreased （P〈0.05）, states that model is successfully established. The weight of high, middle and low dose group of ASMq and positive control group was apparently higher than that of depression model group, and the difference was statistically significant （P 〈0.05）. Compared with normal group, Hipp- ocampal FGF2 and VEGF and the expressive levels of FGF2 mRNA and VEGF mRNA in model control group are all decreased （P〈0.05）. Compared with model control group, Hippoeampal FGF2 protein and VEGF protein and the expressive levels of VEGF mRNA and FGF2 mRNA all increased （P〈0.05）. Conclusion ASMq may could have anti depression effect by increasing the expressive levels of VEGF and FGF2.