褐藻多糖的镇静催眠作用

目的:观察褐藻多糖对小鼠自发活动的影响,评价其抗惊厥,催眠和抗焦虑的作用。方法:①实验于2002-12/2003-05在南方医科大学药学院药理学教研室完成。选用健康成年昆明种小鼠250只,SD大鼠50只。②观察褐藻多糖对小鼠自发活动的影响:选取75只小鼠,随机分为5组:空白对照组(按0.1mL/10g的量灌胃蒸馏水),盐酸氯丙嗪组(在测试自发活动前30min按5mg/kg剂量腹腔注射盐酸氯丙嗪),低、中、高剂量褐藻多糖溶液组(分别按88.73,266.19,798.57mg/kg剂量灌胃褐藻多糖溶液),每组15只。给药2次/d,给药7d。采用YLS-1A多功能小鼠自主活动记录仪测定小鼠5min内自发活动次数。③观察褐藻多糖对小鼠催眠的影响:选取75只小鼠,分组及各组干预措施同“自发活动实验”。末次给药30min后腹腔注射戊巴比妥钠阈下催眠剂量30mg/kg,以翻正反射消失为指标,记录翻正反射消失的动物数。④观察褐藻多糖对小鼠惊厥的影响:取小鼠100只,随机分为5组:空白对照组,盐酸氯丙嗪组,低、中、高剂量褐藻多糖溶液组,每组20只。其中盐酸氯丙嗪组按1mg/kg剂量灌胃地西泮,其余各组分组及给药情况同“自发活动实验”。末次给药1h后按60mg/kg剂量腹腔注射5g/L戊四唑溶液,以出现阵发性抽搐为指标,观察每组发生惊厥的动物数。⑤观察褐藻多糖对大鼠焦虑的影响:应用大鼠Vogel冲突饮水实验模型。选取SD大鼠50只,随机分为5组:空白对照组(按1mL/100g的量灌胃蒸馏水),地西泮组(按1mg/kg剂量灌胃地西泮),低、中、高剂量褐藻多糖溶液组(分别按61.78,185.34,556.02mg/kg剂量灌胃褐藻多糖溶液),每组10只。2次/d,连续给药7d。实验分两阶段进行。大鼠禁水24h后进行无电击饮水训练(自发饮水训练),继续禁水24h再行饮水与电击结合实验(舔水与电击次数之比为20∶1),记录该期间大鼠舔水次数。⑥计量资料差异比较采用单因素方差分析,并用LSD法进行组间多重比较。计数结果差异比较采用χ2检验。结果:小鼠250只和大鼠50只均进入结果分析。①褐藻多糖对小鼠自发活动和戊巴比妥钠诱导的小鼠阈下睡眠的影响:中、高剂量褐藻多糖溶液组能明显减少小鼠的自发活动数,各剂量褐藻多糖溶液组能明显增强阈下剂量戊巴比妥钠诱导的小鼠翻正反射消失的作用,且该作用具有显著的剂量依赖性(P<0.01)。②褐藻多糖对戊四唑诱发的小鼠惊厥的影响:褐藻多糖连续给药7d,中剂量褐藻多糖溶液组能明显抑制戊四唑诱导的小鼠惊厥的作用,褐藻多糖对小鼠惊厥的抑制作用具有一定的剂量依赖性(P<0.05)。③褐藻多糖对大鼠焦虑的影响:褐藻多糖在较低剂量(61.78mg/kg和185.34mg/kg)时对大鼠的自发饮水次数无明显影响,只有在高剂量(556.02mg/kg)时增加大鼠的饮水次数,地西泮也在较高剂量(1.0mg/kg)时增加大鼠饮水次数。进一步的Vogel冲突实验显示,褐藻多糖在61.78,185.34和556.02mg/kg剂量下其抗焦虑作用呈现典型的钟型剂量-效应关系,有效剂量为185.34mg/g。结论:褐藻多糖有明显的镇静催眠、抗惊厥及抗焦虑的作用,且呈一定剂量依赖性,褐藻多糖的抗焦虑作用与地西泮类似。

Sedative and hypnotic effect of sulfated polysaccharide from brown seaweed

BACKGROUND: The upward attack of drug-heat is a special type of syndromes of coexistence of cold and heat, it influence the treatment and conversion of the primary disease.OBJECTIVE: To investigate the pathophysiological basis of upward attack of drug-heat.DESIGN: A randomized and controlled observation. SETTING: Department of Traditional Chinese Medicine (TCM) of the People' s Central Hospital of Huizhou City.PARTICIPANTS: Totally 427 patients with cold syndrome, visiting on Department of TCM of the People's Central Hospital of Huizhou City from January 1996 to December 2001, were given warm-heat remedy. Among them 66 cases, 30 males and 36 females, got upward attack of drug-heat during the process of treatment were enrolled. All these subjects, according to their visiting order, at a ratio of 2:1, were chosen as treatment group (44 cases) and control group (22 cases).METHODS: For the patients in treatment group: Rhubarb 6 g was added boiling water 100 mL and soaked for 8 minutes, then the soaking solution was given to the patients, once a day, for 3 days successively. For patients in control group: Table salt 6 g was added boiling water 100 mL for soaking for 8 minutes, after the salt was completely dissolved, the solution was given to the patients, once a day for 3 days successively. The patients of the two groups were at the same time given remedy to treat cold syndrome. The changes of free triiodothyronine (FT3), free thyronine (FT4), high sensitizing thyroid-stimulating hormone (HS-TSH) and cortisol of the patients were detected before and after administration of warm-heat remedy, before and after medication with rhubarb. MAIN OUTCOME MEASURES: ① The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of warm-heat remedy. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of rhubarb. ③ Comparison of the therapeutic effects in the two groups.RESULTS: All 66 patients involved entered the final result analysis. ①The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of warm-heat remedy: FT3 and FT4 were decreased as compared with those before treatment (2.51±1.20),(6.50±2.30); (10.01±3.21), (15.50±6.31) pmol/L], but HS-TSH and cortisol were increased as compared with those before treatment (8.25 ±3.75),(4.11±1.75) mU/L; (0.56±0.17), (0.43±0.10) μmol/L]. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of rhubarb: FT3 and FT4 ywere increased as compared with those before treatment(4.71 ±1.56), (2.45±1.25); (14.21 ±4.61),(10.21±3.52) pmol/L], but HS-TSH and cortisol were decreased as compared with those before treatment (6.24±2.25), (8.35±3.51) mU/L; (0.48±0.10),(0.60±0.17) μmol/L]. ③ Comparison of the therapeutic effects in the two groups: The rate of excellenly effect in treatment group was obviously higher than that in control group (33%, 5%).CONCLUSION: The pathophysiological basis of upward attack of drug heat is stress state of the body, the secretions of the pituitary-thyroid axis play a role of physiological protection, the adrenocortical function is hyperactive, and rhubarb can control this stress state through inhibiting the metabolism of the body.