BACKGROUND: Pholidota chinensis lindl (PCL) has been used in folk medicine to treat pulmonary edema, resolve phlegm, relieve cough and resist fatigue. However, its pharmacological effects on hypoxic-ischemic heart and brain damage remain to be unclear.OBJECTIVE: To investigate the effects of PCL extract on survival duration of 5 kinds of anoxia models as well as anti-fatigue and anti-hypoxia actions.DESIGN: Randomized and controlled experiment.SETTING: Pharmacological Department of Garnnan Medical College.MATERIALS: The experiment was performed in the Pharmacological Department of Gannan Medical College frgm March to June 2004. A total of 170 Kunming mice, 25 males and 95 females, weighing (20±2) g, were provided by the Experimental Animal Center of Gannan Medical College.METHODS:①Hypoxia-resisting test:Totally 40 mice were randomly divided into 4 groups: normal saline group, hydrochloric propranolol group (0.02 g/kg), and 5 g/kg and 10 g/kg PCL extract groups, with 10 in each group. Twenty minutes after administration, the mice were put into hypoxic wide-mouthed bottles of 250 mL volume with sodalime for recording survival time with stopwatch. ② Test of specific anoxic myocardium: Totally 30 mice were randomly divided into 3 groups with 10 in each, namely normal saline + isoproterenol group, 10 g/kg PCL extract + isoproterenol group, and hydrochloric propranolol (0.02 g/kg) + isoproterenol group.0.015 g/kg isoproterenol was given to mice in each group. Forty minutes after administration, the mice were put into hypoxic wide-mouthed bottles of 250 mL volume with sodalime for recording survival time with stopwatch. ③ Test of NaNO2-induced hypoxia: Forty mice were randomly divided into 4 groups: normal saline group, hydrochloric propranolol group (0.02 g/kg), 5 g/kg and 10 g/kg PCL extract groups, with 10 in each group. Forty minutes after administration, the mice were intraperitoneally injected with 200 mg/kg NaNO2. The survival time was recorded.④Test of cerebral ischemia and hypoxia: Thirty mice were randomly divided into 3 groups: normal saline group, 5 g/kg and 10 g/kg PCL extract groups, with 10 in each group. Forty minutes after administration, the gasping time was recorded. ⑤ Test of exercise tolerance: Thirty mice were randomly divided into normal saline group, 5 g/kg and 10 g/kg PCL extract groups, with 10 in each group. Forty minutes after administration, the mice swam with lead load on the tails, which was 2% of the body weight. The swimming test for mice used a circular pool 40 cm in diameter and 30 cm in height, and filled with water to a depth of 25 cm. Water was kept at 20-22 ℃.To study the effects of PCL extract on exercise tolerance, the swimming time of the mice was recorded until they were exhausted, submerged for 8 seconds, and did not float onto the surface again.MAIN OUTCOME MEASURES: The survival time and gasping duration in the hypoxia models after administration.RESULTS: Totally 170 mice entered the final analysis. ① Hypoxia-resisting test: Survival time was longer in 5 g/kg and 10 g/kg PCL extract groups than that in normal saline group and hydrochloric propranolol group (F=70.52, P ＜ 0.05); survival time was longer in 10 g/kg PCL extract anoxic group than in 5 g/kg PCL extract group (P ＜ 0.05). ② Test of specificmyocardium: Survival time was longer in 10 g/kg PCL extract + isoproterenol group and hydrochloric propranolol + isoproterenol group than in saline + isoproterenol group (F=37.29, P ＜ 0.05).③ Test of NaNO2-induced hypoxia: Survival time was longer in hydroch loric propranolol group,5 g/kg and 10 g/kg PCL extract groups than in saline group (F=34.34, P＜ 0.05); survival time was longer in 10 g/kg PCL extract group than in 5g/kg PCL extract group(P<0.05).④Test of cerebral ischemia and hypoxia Gasping time was longer in 5 g/kg and 10 g/kg PCL extract groups than in saline group (F=41.00, P ＜ 0.05); gasping time was longer in 10 g/kg PCL extract group than in 5 g/kg PCL extract group (P ＜ 0.05).⑤Test of exeract tolerance:Survival time was longer in 5g/kg and 10 g/kg PCL extract groups than in saline group (F=33.09, P ＜ 0.05);survival time was longer in 10 g/kg PCL extract group than in 5 g/kg PCL extract group (P ＜ 0.05).CONCLUSION: PCL has anti-fatigue and anti-hypoxia effects in a dosage-dependent manner. The effects may be related to Na, K-ATPase change or increase of alveolar fluid clearance.%背景:石仙桃常用于清肺、化痰止咳和抗疲劳等作用,但有关其对心脑缺血缺氧的药理学作用尚未见报道.目的:观察石仙桃提取液对5种缺氧模型小鼠存活时间的影响,探讨其对小鼠的抗疲劳和耐缺氧的保护作用.设计:随机对照实验观察.单位:赣南医学院药理学教研室.材料:实验于2004-03/06在赣南医学院药理教研室完成.取昆明种小鼠170只,雄性25只,雌性95只,体质量(20±2)g,由赣南医学院实验动物中心提供.方法:①常压耐缺氧实验:取40只小鼠随机分为4组,即生理盐水组、盐酸普萘洛尔组(0.02 g/kg)、石仙桃提取液5 g/kg,10 g/kg组,每组10只.给药20min后,将小鼠放置在密封的含钠石灰的广口瓶中,秒表记录存活时间.②特异性心肌缺氧实验:取30只小鼠随机分为3组,即生理盐水+异丙肾上腺素组、盐酸普萘洛尔(0.02 g/kg)+异丙肾上腺素组、石仙桃提取液10 g/kg+异丙肾上腺素组,每组10只.其中各组小鼠均给予异丙肾上腺素0.015 g/kg.给药40 min后,小鼠放置在密封的含钠石灰的广口瓶中,用秒表记录存活时间.③亚硝酸钠引起的缺氧实验:取40只小鼠随机分为4组,即生理盐水组、盐酸普萘洛尔组(0.02 g/kg)、石仙桃提取液5 g/kg,10 g/kg组,每组10只.给药40 min后,腹腔注射200mg/kg亚硝酸钠,分别记录小鼠存活时间.④对抗脑缺血缺氧实验:取30只小鼠,随机分为3组,即生理盐水组、石仙桃提取液5 g/kg,10 g/kg组,每组10只.其中盐酸普萘洛尔组给予盐酸普萘洛尔0.02 g/kg.给药40 min后,麻醉后断头,分别记录小鼠喘息时间.⑤运动耐力实验:取30只小鼠随机分为3组,即生理盐水组、石仙桃提取液5 g/kg,10 g/kg组,每组10只.给药40 min后,在小鼠尾根部负体质量2%的铅皮,放入水深25 cm、直径40 cm、桶高30 cm的水桶中,每桶同时放进1只小鼠,用秒表立即记录自游泳开始至力竭下沉8 s,且不浮出水面为止的时间,计为小鼠游泳时间.主要观察指标:给药后各组小鼠的存活时间和喘息时间.结果:纳入170只小鼠,全部进入结果分析,无脱失.①常压耐缺氧实验:石仙桃提取液5 g/kg,10 g/kg组小鼠的生存时间显著长于生理盐水组和盐酸普萘洛尔组(F=70.52,P＜0.05),石仙桃提取液10 g/kg组显著长于石仙桃提取液5 g/kg组(P＜0.05).②特异性心肌缺氧实验:石仙桃提取液10 g/kg+异丙肾上腺素组和盐酸普萘洛尔+异丙肾上腺素组小鼠的生存时间显著长于生理盐水+异丙肾上腺素组(F=37.29,P＜0.05).③亚硝酸钠所致缺氧实验:盐酸普萘洛尔组、石仙桃提取液5 g/kg,10 g/kg组小鼠的生存时间显著长于生理盐水组(F=34.34,P＜0.05),石仙桃提取液10 g/kg组显著长于石仙桃提取液5 g/kg组(P＜0.05).④对抗脑缺血缺氧实验:石仙桃提取液5 g/kg,10 g/kg组小鼠的喘息时间显著长于生理盐水组(F=41.00,P＜0.05),石仙桃提取液10 g/kg组显著长于石仙桃提取液5 g/kg组(P＜0.05).⑤运动耐力实验:石仙桃提取液5 g/kg,10 g/kg组小鼠的存活时间显著长于生理盐水组(F=33.09,P＜0.05),石仙桃提取液10 g/kg组显著长于石仙桃提取液5 g/kg组(P＜0.05).结论:石仙桃具有抗疲劳及耐缺氧作用,且呈剂量依赖性,这种作用可能与影响Na,K-ATP酶或提高肺泡液清除作用有关.
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