【摘要】 目的:观察一种拟青霉代谢物提取物对慢性应激抑郁模型大鼠24h糖水消耗量、脾淋巴细胞增殖和血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平的影响。方法:实验于2005-08在安徽医科大学药理学教研室完成。①选用健康成年雄性SD大鼠48只,按随机数字表法分为6组:对照组、模型组、吗氯贝胺组、拟青霉代谢物提取物高、中、低剂量组,每组8只。用药组与模型组大鼠造成抑郁模型:单只孤养,每天随机给予不同的刺激,包括:电击足底、4℃冷水刺激5min、45℃热刺激5min、高速水平摇晃10min、夹尾60s、禁水24h、禁食48h、悬吊5min和昼夜颠倒,平均每种刺激各2次,共21d。用药组于造模结束后灌胃给药,1次/d,共21d。模型组及对照组按10mL/kg灌胃蒸馏水\吗氯贝胺组:按40mg/kg剂量灌胃吗氯贝胺混悬液(单胺氧化酶抑制剂;上海信谊百路达药业有限公司,批号:031001,0.15g/片);拟青霉代谢物提取物高、中、低剂量组:分别按80,40,20mg/kg剂量灌胃拟青霉代谢物提取物混悬液(安徽农业大学虫生真菌研究所提供,1.25kg/L,批号:20050112)。②给药第21天,计算大鼠24h糖水消耗量,以反映大鼠快感缺乏情况。用四甲基偶氮唑盐法检测大鼠脾淋巴细胞增殖情况;用放射免疫法测定血清中白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平。结果:SD大鼠48只均进入结果分析。①24h糖水消耗量:模型组明显低于对照组,分别为(40.1±9.0),(66.2±15.7)mL,(P<0.01)。拟青霉代谢物提取物高、中剂量组和吗氯贝胺组明显高于模型组,分别为(57.4±12.6),(54.6±11.5),(59.4±16.7)mL,(P<0.05～0.01)。②细胞增殖:模型组大鼠脾细胞淋巴细胞对刀豆蛋白A刺激的T淋巴细胞增殖、脂多糖刺激的B淋巴细胞增殖均有明显的抑制作用,A值明显低于对照组(P<0.01)。高、中、低剂量拟青霉代谢物提取物和吗氯贝胺(40mg/kg)可使T淋巴细胞增殖的抑制状态得到明显改善,高、中剂量拟青霉代谢物提取物和吗氯贝胺(40mg/kg)可使B淋巴细胞增殖的抑制状态得到明显改善,A值明显高于模型组(P<0.05～0.01)。③血清细胞因子水平变化:模型组大鼠血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平明显高于对照组(P<0.05～0.01)。拟青霉代谢物提取物高、中剂量组血清肿瘤坏死因子α水平明显低于模型组(P<0.05),拟青霉代谢物提取物各剂量组血清白细胞介素6、白细胞介素1β水平明显低于模型组(P<0.05),吗氯贝胺组血清白细胞介素6水平明显低于模型组(P<0.05)。结论:拟青霉代谢物提取物可改善抑郁大鼠快感缺乏,该作用的发挥可能与调节免疫功能和细胞因子水平有关;该提取物的上述作用以80,40mg/kg的高、中剂量较为明显,且与吗氯贝胺作用效果相当。更多还原

【Abstract】 AIM:To explore the effect of bioactive compound from paecilomyces tenuipes(BCPT)on the sweet water consumption and lymphocyte proliferation and the blood level of interleukin-1(IL-1β),IL-6,and tumor necrosis factor(TNF-α)of rats with chronic stress depression.METHODS:The experiment was conducted in the Department of Pharmacology,Anhui Medical University in August 2005.①Forty-eight healthy adult male SD rats were selected and randomly divided into 6 groups:control group,model group,moclobemide group,BCPT 80 mg/kg,40 mg/kg and 20 mg/kg groups with 8 rats in each group.The models of depression of the administration groups and model group were established:The rats were fed separately,and given different stresses everyday including electric stimulation to foot,4 ℃ cold water stimulation for 5 minutes,45 hot stimulation for 5 minutes,horizontally weaving at high speed for 10 minutes,tail clipping for 60 seconds,water deprivation for 24 hours,fasting for 48 hours,suspending for 5 minutes and reversal of day and night.Each kind of stimulation was performed twice for 21 days.The administration groups were intragastrically infused with separately medicine after modeling,once daily for 21 days.The model group and control group were infused with 10 mL/kg distilled water;moclobemide group was infused 40 mg/kg moclobemide suspension(monoamine oxidase inhibitor provided by Shanghai Xinyi Bailuda Pharmaceutically Co.,Ltd,No.031001,0.15 g per pill);the BCPT 80 mg/kg,40 mg/kg and 20 mg/kg groups were infused BCPT suspension at three doses(provided by the Institute of Vertivillium Lecanii,Anhui Agricultural University,1.25 g/L,No.20050112).②The sweet water consumption was calculated at the 21st day of administration to observe the anhedonia condition of rats.The proliferation of T-lymphocyte and B-lymphocyte were measured by MTT assay and the blood level of TNF-α,IL-1β,IL-6 were measured by radioimmunoassay.RESULTS:All the 48 rats were involved in the result analysis.①Sweet water consumption in 24 hours:The model group was obviously lower than the control group [(40.1±9.0),(66.2±15.7)mL,P < 0.01];the high and middle doses BCPT groups and moclobemide group were significantly higher than the model group [(57.4±12.6),(54.6±11.5),(59.4±16.7)mL,P < 0.05-0.01].②Cell proliferation:The lymphocyte of splenocyte of rats in the model group showed obvious inhibitory effect on the proliferation of T-lymphocyte and B-lymphocyte,and the A value was obviously lower than the control group(P < 0.01);High and middle doses BCPT and moclobemide(40 mg/kg)could improve the inhibitory effet on T-lymphocyte,while the high and middle doses BCPT and moclobemide(40 mg/kg)could markedly improve this inhibitory effect,and the A value was higher than the model group(P < 0.05-0.01).③Changes of serum cell factor:The blood levels of TNF-α,IL-1β and IL-6 in the model group were obviously higher than the control group(P < 0.05-0.01).Compared with the model group,the blood level of TNF-α of the BCPT 80 mg/kg and 40 mg/kg groups were much lower(P < 0.05),and the levels of IL-6 and IL-1β of the high,middle and low doses BCPT groups were significantly lower than the model group(P < 0.05).The level of IL-6 of the moclobemide group was also lower than the model group(P < 0.05).CONCLUSION:BCPT can improve the anhedonia condition of rats with depression,which may related with the regulation of immunological function and cell factor levels;high and middle doses BCPT present better effects,which is similar to that of moclobemide.更多还原