地奥心血康对高脂血症大鼠血脂及脂蛋白的影响

研究地奥心血康对高脂血症大鼠血脂及脂蛋白的影响。用高脂饲料喂服雄性ｗｉｓｔａｒ大鼠,复制高脂血症大鼠模型。动物分５组：１、正常对照组：给予基础饲料＋生理盐水。２、高脂模型组：高脂饲料＋生理盐水。３－４、地奥心血康０１０、０２０ｇ／ｋｇ组：高脂饲料＋地奥心血康;５、阳性药肌醇烟酸酯组：高脂饲料＋肌醇烟酸酯（０１ｇ／ｋｇ）,连续灌胃给药１０ｄ后采血,测定血清甘油三脂（ＴＧ）,总胆固醇（ＴＣ）,高密度脂蛋白（ＨＤＬ－Ｃ）,计算低密度脂蛋白（ＬＤＬ－Ｃ）。地奥心血康０２０、０１０ｇ／ｋｇ均能明显降低高脂血症大鼠ＴＣ、ＴＧ、ＬＤＬ－Ｃ（Ｐ＜００５Ｐ＜００１（与高脂模型组比）,分别使ＴＣ降低３０％、１９％;ＴＣ降低４５％、２０％;使ＬＤＬ－Ｃ降低５７％、３１％;０２０ｇ／ｋｇ也能升高ＨＤＬ－Ｃ,为１２％。地奥心血康能降低高脂血症大鼠ＴＣ、ＴＧ、ＬＤＬ－Ｃ水平而升高ＨＤＬ－Ｃ水平     

Acute toxicity and sub-chronic toxicity of steroidal saponins from Dioscorea zingiberensis C.H.Wright in rodents

Ethnopharmacological relevance

Steroidal saponins from Dioscorea zingiberensis are widely used in China for curing cardiovascular diseases. However, there was little toxicological information available on them.

Aim of the study

The study evaluated potential toxicity of the steroidal saponins and analyzed the metabolites in rats.

Materials and methods

For the acute study, the steroidal saponins were administered to kunming mice in single doses of 112.5–9000 mg/kg given by gavage. General behavior adverse effects, mortality and liver histopathological changes were examined. For the sub-chronic toxicity study, Sprague–Dawley rats were gavaged at doses of 127.5, 255 and 510 mg/kg/day for 30 days, then examined the biochemical and hematological parameters. Metabolites in serum were analyzed by HPLC–MS.

Results

The steroidal saponins caused dose-dependent general behavior adverse effects, mortality and liver histopathological changes in the acute toxicity study. In the sub-chronic toxicity study, 510 mg/kg/day of steroidal saponins increased total bilirubin (TBIL) in serum and decreased protein content in liver significantly. The metabolic process of TBIL in liver includes TBIL intaking, conjugated bilirubin forming, conjugated bilirubin excreting to biliary passage. Treatment with high dose of the steroidal saponins in vivo may lead to vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis. In all doses used in the experiment, the steroidal saponins decreased aspartate aminotransferase (GOT), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) in serum and increased reduced glutathione hormone (GSH), glutathione reductase (GR) and glutathione S-transferases (GST) in liver. Diosgenin was the main metabolite in serum.

Conclusions

The steroidal saponins did not show any sign of toxicity up to oral dose of 562.5 mg/kg in mice. No significant changes of biochemical and hematological parameters in rats (except at 510 mg/kg/day), it was concluded that the steroidal saponins did not appear to have significant toxicity in their traditional uses.     

地奥心血康治疗缺血性脑血管疾病

用地奥心血康２００ｍｇ，ｐｏ，ｔｉｄ，连用３０ｄ，治疗脑梗死３０例（男性１７例，女性１３例；年龄６３±ｓ１７ａ）和椎基底动脉供血不足３７例（男性１８例，女性１９例；年龄６１±９ａ），与对照组口服复方丹参片３片（０．９ｇ）ｔｉｄ加氟桂利嗪５ｍｇ，ｂｉｄ进行比较。地奥心血康的有效率分别为９０％和１００％，而对照组分别为８３％和９４％。对椎基底动脉供血不足，地奥心血康组优于照组（Ｐ＜０．０５）。提示地奥心血康具有良好的促进脑血管循环作用。     

地奥心血康胶囊治疗心绞痛713例

冠心病心绞痛患者７１３例（男性３９８例，女件３１５例；年龄５８±ｓ６ａ），口服地奥心血康胶囊２００ｍｇ，ｔｉｄ，共２ｍｏ。２ｍｏ后，３９９例继续口服１００ｍｇ，ｔｉｄ，共４ｍｏ。结果：２ｍｏ的临床总有效率为９０．３％，心电图总有效率为５１．７％。该药能明显抑制血小板聚集，降低血胆固醇和甘油三酯。不良反应轻微。     

地奥心血康治疗梅尼埃病与氟桂利嗪的比较

梅尼埃病患者６２例，分为２组。３４例（年龄５８±ｓ１４ａ）口服地奥心血康２００ｍｇ，ｔｉｄ；２８例（年龄５３±１０ａ）服氟桂利嗪５ｍｇ，ｂｉｄ（加烟酸１００ｍｇｔｉｄ或长春西汀片５ｍｇｔｉｄ），疗程均为７ｄ。２组的有效率分别为９４％和８２％（Ｐ＞０．０５）。地奥心血康起效快，症状消失早，无不良反应，提示该药对梅尼埃病有良好疗效。     

地奥心血康的长期毒性试验

大鼠ｉｇ地奥心血康（ＤＡＸＸＫ）２２５ｍｇ／ｋｇ，４５０ｍｇ／ｋｇ及９００ｍｇ／ｋｇ（约为临床剂量１８０倍），ｑｄ×４ｍｏ，除高剂量组体重增长较慢外，无其他毒性发现。狗ｐｏＤＡＸＸＫ６．３ｍｇ／ｋｇ及２５２ｍｇ／ｋｇ（约为临床剂量５０倍），ｑｄ×６ｍｏ，体重增长相似，血、尿常规，谷丙转氨酶（ＧＰＴ）、尿素氮等肝肾功能指标均正常，心电图未见明显变化，组织学检查及主要脏器系数均正常。关键词     

地奥心血康治疗偏头痛

目的：观察地奥心血康治疗偏头痛是否有效。方法：偏头痛７２例，男性２９例，女性４３例，年龄３７±ｓ７ａ，剂量２００－３００ｍｇ，ｐｏ，ｔｉｄ，治疗时间１－３ｍｏ，结果：治疗前头痛单位指数０．３９±０．２５，治疗后为０．１２±０．１３（Ｐ＜０．０１）。发作频数明显减少。２９例血小板聚集率由治疗前７１％±８％降至治疗后６３％±７％（Ｐ＜０．０１）。该药不良反应轻微。结论：地奥心血康可用以防治偏头痛。     

地奥心血康对心肌缺血再灌注损伤的抗脂质过氧化作用的研究

目的:揭示地奥心血康(DK)对心肌缺血再灌注损伤的抗氧化作用与机制。方法:用成年杂种犬复制心肌缺血再灌注损伤模型。多道生理记录仪监测心功能指标;酶法测定AST、CK、LDH含量;荧光法测血清与心肌细胞膜MDA含量;电子自旋共振(ESR)记录微分谱线进行体外羟自由基捕捉实验。结果:①生理盐水对照(NS)组随着缺血再灌注时间的延长,LVSP,±dp/dt_max呈进行性下降;而DK组缺血再灌注后LVSP和±dp/dt_max虽有下降,但显著高于NS组(P＜0.05);②血清中AST,CK,LDH含量随缺血/再灌时间延长均增高,于再灌120min后DK显著低于NS组(P＜0.05);③血清MDA含量于再灌注240min时DK组显著低于NS组(P＜0.05);④DK组心肌细胞膜MDA含量也显著地低于NS组(P＜0.05);⑤在DK浓度为0.71%、1.43%和2.14%时,羟自由基强度分别减少66%、80%和100%。结论:DK对心肌缺血再灌注损伤犬的心功能和心肌细胞膜有明显的保护作用,其很强的清除羟自由基的功能是实现这种保护效应的重要机制。     

地奥心血康对小鼠心肌营养性血流量的影响

采用放射性核素８６Ｒｂ测定小鼠心肌营养性血流量的方法。用地奥心血康８０ｍｇ／ｋｇ，ｉｇ或４０ｍｇ／ｋｇ，ｉｐ，均能增加心肌营养性血流量。＊Ｐ＜０．０１。讨论小鼠心肌对８６Ｒｂ摄取量的大小，在很大程度上取决于心肌内开放毛细血管的数量和面积，在一定条件下，心肌血流量愈大，对８６Ｒｂ的摄取量愈多，所以，心肌对８６Ｒｂ的摄取量可以代表心肌营养血流量。采用８６Ｒｂ测定心肌营养性血流量报道较多，但处理心脏的方法有组织研磨法［２］，组织消化法［３］和直接测定法［１，４］。本文采用直接测定法［１］，操作比较简便。关于注射８６ＲｂＣｌ后处死动物时间的选择，施新献认为心脏对８６Ｒｂ的摄取是一个动态过程，在注射后３０ｓ至１５ｍｉｎ的阶段内，心肌８６Ｒｂ含量高且平稳。因此，选择静注后３０ｓ作为观察心肌对８６Ｒｂ摄取能力的时间标准是比较合适的［５］。地奥心血康４０，８０ｍｇ／ｋｇ，ｉｐ和８０ｍｇ／ｋｇ，ｉｇ，均有不同程度地增加小鼠心肌营养性血流量作用，其中８０ｍｇ／ｋｇ，ｉｐ与双嘧达莫１００ｍｇ／ｋｇ，ｉｐ能显著增加小鼠心肌营养性血流量，其作用强度相似，与生理盐水组比较Ｐ＜０．０１。但地奥心血康２００ｍｇ／ｋｇ１次ｉｇ，反而减少心肌?     

地奥心血康对麻醉犬及清醒兔急性心肌梗死的影响

用麻醉犬和清醒兔冠状动脉结扎造成心肌梗死模型，采用心外膜电图标测和定量组织学方法，研究了地奥心血康（ＤＡＸＸＫ）静脉给药（犬）及消化道给药（兔）对心肌梗死的影响。结果证明ＤＡＸＸＫ能明显减轻心肌缺血，缩小梗死范围。