生姜对半夏所致刺激性炎症反应的影响
|
摘要
本学位论文得到国家自然基金项目——半夏刺激性毒性的物质基础及炮制解毒机理研究(NO.30772785)、国家自然基金项目——天南星科有毒中药矾制解毒共性规律研究(NO.30973939)、国家“十一五”科技部支撑计划课题——复制法炮制解毒共性技术和相关设备研究(NO.2006BAI09806-10)的资助。
半夏为天南星科植物半夏Pinellia ternata(Thunb.)Breit的块茎。自古以来,因其味辛辣、麻舌而刺喉,具有“戟人咽”的刺激性,被列为有毒中药。临床误服或使用不当,可致强烈的皮肤、粘膜接触性的刺激性毒性。本课题组前期研究表明半夏刺激性毒性成分为其含有的具有特殊晶型的“毒针晶”。半夏生品及毒针晶均可引起家兔眼结膜强烈水肿,使小鼠毛细管通透性增强,腹腔渗出液中炎症介质PGE2含量增加,其毒性表现与炎症效应极为相似。课题组进一步研究发现半夏毒针晶是主要由草酸钙、蛋白组成的复合物,其中蛋白含量为6.084%；毒针晶上带有凝集素蛋白,该蛋白能显著引起大鼠腹腔中性粒细胞向腹腔迁移和大鼠足趾肿胀。毒针晶中加入凝集素后,可显著加重炎症反应。这些结果表明半夏的刺激性毒性作用是由毒针晶的机械损伤加上凝集素蛋白的化学损伤双重作用产生。
中医临床上半夏中毒用生姜解毒。传统中医理论认为：“半夏性畏生姜,用之以制其毒,功益彰”。梁·陶弘景《本草经集注》中记载“半夏毒,用生姜汁,煮干姜汁并解之”。但生姜解半夏毒的机理不明。现代研究发现生姜具有抗炎镇痛、调节免疫等药理活性。而半夏毒针晶可引起强烈的炎症反应。故本学位论文提出假说“半夏的刺激性毒性在机体可表现为刺激性炎症毒性,生姜对半夏的解毒作用与其拮抗半夏所致的刺激性炎症毒性相关”。本学位论文据此设计了研究路线。
本学位论文采用多种炎症模型,以半夏毒针晶为致炎剂,发现半夏毒针晶可引起强烈的炎症毒性反应。研究表明生姜汁确实能显著拮抗半夏毒针晶所致的炎性作用,并筛选得出姜辣素类成分是生姜拮抗半夏毒针晶所致炎性反应的有效部位,其拮抗半夏所致炎症反应的机制不是通过兴奋肾上腺分泌肾上腺皮质激素而发挥作用,可能与抑制半夏毒针晶诱导的炎症介质的合成与释放有关。同时发现姜辣素类成分可拮抗半夏毒针晶中的主要化学刺激物(凝集素蛋白)的致炎效应。主要工作内容和研究结果包括以下几方面：
1半夏毒针晶的致炎作用研究
采用小鼠毛细管通透性试验、小鼠腹腔炎症试验及大鼠足趾肿胀试验,考察不同浓度半夏毒针晶所致的炎症毒性效应及其量-毒关系。研究结果表明：腹腔注射半夏毒针晶混悬液可使小鼠腹腔毛细血管通透性增加,腹腔渗出液中炎症介质PGE2含量增加,也可引起大鼠足趾肿胀,并在一定剂量范围内表现为典型的量-毒关系。此结果说明半夏毒针晶可诱导炎症,毒针晶的刺激性毒性在机体内主要表现为炎症反应。
2生姜汁对半夏毒针晶所致炎性反应的影响
采用半夏毒针晶所致小鼠腹腔炎症模型,观察生姜汁对小鼠毛细管通透性、腹腔渗出液中蛋白质含量、白细胞数量的影响；采用半夏毒针晶诱导大鼠足趾肿胀模型,观察生姜汁对半夏毒针晶所致大鼠足趾肿胀的影响。研究结果表明：生姜汁能显著抑制半夏毒针晶腹腔注射所致的小鼠毛细管通透性增加,减少腹腔渗出和白细胞数目,降低渗出液中蛋白质的含量,亦可减轻半夏毒针晶所致的大鼠足趾肿胀,说明生姜汁确实可拮抗半夏毒针晶所致的炎症反应,且其中高剂量组的拮抗效应与阳性药阿司匹林组相当。
3生姜各部位的提取及相关成分含量测定
生姜挥发油部位采用水蒸气蒸馏的方法提取,并采用气质联用法对其组分进行分析；生姜姜辣素部位为生姜经乙酸乙酯提取后去除挥发油后精制所得,并采用紫外分光光度法对姜辣素部位中总姜辣素含量进行测定,采用HPLC法对姜辣素部位中6-姜酚(6-gingerol)、6-姜烯酚(6-shogaol)进行含量测定；生姜乙酸乙酯提取后的药渣经水提取得到药渣水提物部位。结果获得挥发油、姜辣素、药渣水提物三个部位；生姜挥发油中共鉴定了64个化合物,主要为萜类物质；生姜姜辣素部位中总姜辣素含量为88.15%,6-姜酚和6-姜烯酚的含量分别为19.40%、8.11%。此结果说明姜辣素部位所含的总姜辣素含量较高,且生姜其他部位的提取方法亦可行,可作为生姜拮抗半夏毒针晶所致炎症的筛选部位。
4生姜各部位对半夏毒针晶所致炎性反应的影响
为筛选生姜中拮抗半夏毒针晶炎性反应的有效部位,采用腹腔注射半夏毒针晶所致小鼠腹腔炎症模型,观察生姜各提取部位对小鼠毛细管通透性、腹腔渗出液中蛋白质含量、白细胞数量的影响；采用半夏毒针晶诱导大鼠足趾肿胀模型,观察生姜各提取部位对大鼠足趾肿胀的作用。研究结果表明：姜辣素部位能显著抑制半夏毒针晶腹腔注射所致的小鼠毛细管通透性增加,降低蛋白质含量和白细胞数目,也可减轻半夏毒针晶所致的大鼠足趾肿胀,而挥发油及药渣水提物未见显著性影响。此结果表明生姜中的姜辣素类成分是拮抗半夏毒针晶所致炎症反应的有效部位。
5姜辣素类成分拮抗半夏毒针晶所致炎性反应机制的初步研究
为探讨姜辣素类成分的拮抗效应是否依赖于下丘脑-垂体-肾上腺皮质系统,采用半夏毒针晶诱导的正常大鼠和去肾上腺大鼠足趾肿胀试验,观察姜辣素类成分对正常大鼠和去肾上腺大鼠足趾肿胀的影响。对正常大鼠两侧肾上腺中胆固醇与VitC含量进行测定,观察姜辣素类成分对肾上腺中胆固醇与VitC含量的影响。同时采用半夏毒针晶诱导的小鼠腹腔炎症模型,观察姜辣素类成分对小鼠腹腔渗出液中PGE2、NO、MDA的影响;采用半夏毒针晶诱导的正常大鼠足趾肿胀模型,观察姜辣素类成分对大鼠炎足中COX-2、PGE2、TNF-α的影响。研究结果表明：姜辣素类成分可显著抑制半夏毒针晶所致的正常大鼠足趾肿胀和去肾上腺大鼠足趾肿胀,且对正常大鼠肾上腺中胆固醇和VitC的合成释放无显著影响,表明姜辣素类成分拮抗半夏毒针晶所致炎性反应不是通过兴奋肾上腺分泌肾上腺皮质激素而发挥作用的。同时,姜辣素类成分可抑制半夏毒针晶所致的小鼠腹腔渗出液中PGE2、NO、MDA的生成,还能显著抑制半夏毒针晶所致大鼠炎足中COX-2、PGE2、TNF-α的生成,提示可能与抑制COX-2、PGE2、TNF-α、NO、MDA的生成有关。
6姜辣素类成分对半夏凝集素所致炎性反应的影响
课题组前期研究表明凝集素蛋白是半夏毒针晶中的主要蛋白,可以引起大鼠腹腔白细胞迁移、渗出液中PGE2含量增加和大鼠足趾肿胀,是半夏毒针晶中引起炎症刺激的主要化学物质。故将提取所得的凝集素作为致炎剂,采用小鼠腹腔炎症模型和大鼠足趾肿胀模型,考察姜辣素类成分对半夏凝集素所致炎症反应的影响。结果显示半夏凝集素可显著引起小鼠腹腔渗出液中PGE2含量增高及大鼠足趾肿胀,并可加重毒针晶的致炎作用；姜辣素类成分可显著抑制半夏凝集素所致的炎症反应,亦可拮抗半夏凝集素与毒针晶协同所致的炎症反应。
通过上述研究表明,半夏毒针晶可引起机体强烈的刺激性炎症毒性,而生姜汁及生姜中的姜辣素类成分能有效拮抗半夏毒针晶所致的炎性反应,并初步阐明姜辣素类成分拮抗半夏毒针晶炎性反应不依赖于肾上腺分泌肾上腺皮质激素系统,其机制可能与抑制毒针晶诱导的炎症因子有关。同时研究进一步证明半夏凝集素是半夏毒针晶中的主要化学刺激物,姜辣素类成分可拮抗半夏凝集素所致的炎性反应。说明生姜确实可以起到解半夏毒的作用,其作用机制是生姜中的姜辣素类成分可直接拮抗半夏毒针晶刺激后产生的炎症反应,减轻毒针晶上的凝集素蛋白所产生的炎症反应。
本学位论文对“生姜解半夏毒”的传统中医理论进行了探索性研究,结果揭示了何为半夏毒,生姜中解半夏毒的成分,并初步揭示了生姜的解毒机制,证实此传统中医理论的科学性,为临床半夏中毒的解毒提供理论基础。本学位论文的研究可为中医理论的现代科学内涵研究提供了较好的借鉴作用。
This project was supported by national natural science foundation (No.30772785, NO. 30973939), "Eleven-Five" national projects of technological supporting (No.2006BAI09B06-10).
Pinellia ternata (Thunb.) Breit. whose tuberous stems are important Chinese medicines, is taxonomically belonged to Araceae family, and are well known for their irritant properties. If chewed and touched raw, the corms of the plants could result in swelling and burning pain in the mucous membranes, and an unbearable itching in skin. The needle-like raphides of calcium oxalate were proved to be their common poisonous components, named as toxic raphides. The raphides caused severe conjunctival edema in rabbit, increased capillary permeability and content of PGE2 in the exudates in mice. Toxic raphide were a complex compsed by mainly calcium oxalate crystals and protein. The content of protein was 6.084%. The study found that the agglutinin on the toxic raphide can significantly induce rat peritoneal neutrophil migration to peritoneal and rat paw edema. These results indicated that the reason of the toxic effects of raphides were the dual role of mechanical damage by calcium oxalate and chemical inflammation induced by agglutinin.
Ginger was used to detoxificate to P. ternate in clinic. Traditional Chinese medicine theory held that "P. ternata feared ginger, and cooked with ginger for detoxification". Tao Hongjing held that "P. ternata was toxic and was detoxificated by ginger juice and dry ginger" However, the mechanism of ginger detoxification to P. ternata was unknown. Modern research showed that ginger had anti-inflammatory, analgesic, immune and other pharmacological activity. This paper was put forward the hypothesis "the irritating toxic of P. ternata in the body can be expressed as an inflammation. Ginger detoxification of P. ternata was related to the antagonistic effect of inflammation caused by P. ternata". This paper was designed according to this line of the research hypothesis.
Inflammation models were used to reseach the raphides. The result found that raphides can cause irritant toxicity, and ginger juice can really antagonize to inflammation induced by the raphides. Gingerols were an effective part of ginger which did not depend on the anti-inflammatory mechanisms of the release of adrenal cortex hormone by activating adrenocorticotropic hormone, and its anti-inflammatory mechanism may be an inhibition of inflammatory mediators induced by the raphides in P. ternate. The result also found that gingerols can inhibit the inflammatory effects caused by P. ternate agglutinin. Main contents and findings were the following:
1. The inflammatory effect induced by raphides in P. ternate
The mouse capillary permeability test, mouse peritonitis and toe swelling of rat induced by the raphides were applied to investigate the inflammatory effects of different concentrations of raphides. The result showed that raphides can increase the capillary permeability, caused the release of inflammatory mediator (PGE2) and toe swelling of rat.
2 Anti-inflammatory effect of ginger juice on inflammation induced by raphides in P. ternate
The mouse peritonitis model induced by the raphides was applied to investigate the anti-inflammatory effects of ginger juice by detecting the capillary permeability, quantity of leukocytes, and the protein content in the exudates. Toe swelling of rat induced by the raphides was used to determine the swelling extent. The result showed that ginger juice exhibited comparable anti-inflammatory effects in terms of the inhibitions on the exudation and leukocytes efflux, and the production of protein. Ginger juice inhibited penetration of capillary vessel in mouse and toe swelling of rat induced by the raphides.
3 Three extracts of ginger and component analysis
Ginger volatile oils, extracted by steam distillation, were analyzed by GC/MS. Gingerols were obtained from ginger which was extracted by ethyl acetate and was removed of volatile oils. The content of total gingerols was determined by UV spectrophotometry. The content of 6-gingeroland 6-shogaol was determined by HPLC. After extracted by the ethyl acetate, ginger dregs were extracted again by water, called as aqueous extract. The result showed that ginger volatile oil, gingerols, and aqueous extract of ginger were obtained. GC/MS analysis showed that there were 64 compounds in volatile oil which were identified mainly terpenoids. The content of total gingerols,6-gingerol, and 6-shogaol were 88.15%,19.40%and 8.11%, respectively. The results were ready to screen the active part from three extracts further.
4 Anti-inflammatory effect of three parts of ginger extract on inflammation induced by raphides in P. ternate
The mouse peritonitis model induced by the raphides induced was applied to investigate the anti-inflammatory effects of three ginger extracts by detecting the capillary permeability, quantity of leukocytes, and the protein content in the exudates. Toe swelling of rat induced by the raphides was used to determine the swelling extent. The result showed that gingerols exhibited comparable anti-inflammatory effects in terms of the inhibitions on the exudation and leukocytes efflux, and the production of protein. Gingerols inhibited penetration of capillary vessel in mouse and toe swelling of rat induced by the raphides. The volatile oils and aqueous extract did not have the anti-inflammatory effects.
5 Anti-inflammatory mechanisms of gingerols related to inhibiting inflammatory by raphides in P. ternate
According to the results of previous studies, toe swelling induced by the raphides of normal rat and toe swelling induced by the raphides of bilaterally adrenalectomized rats were used to determine the swelling extent. The contents of VitC and cholesterol were measured in normal adrenal glands. The result showed that gingerols had a significantly suppressive effect on paw edema of normal rat and adrenalectomized rat induced by raphides and had no effect on the contents of VitC and cholesterol in normal adrenal glands. The result showed gingerols had an anti-inflammatory effect, which were independent on pituitary-adrenal axis.
The content of PGE2, NO and MDA in the mouse exudate were respectively measured in rats with acute peritonitis induced by raphides. The activity of COX-2 and the content such as PGE2, TNF-a were examined in the toe of rats induced by raphides. The result showed that gingerols significantly inhibited the production of NO, PGE2, and MDA in exudate of peritonitis rats. Furthermore, gingerols inhibited the activity of COX-2, and reduced the production of PGE2 and TNF-a in the toe. The anti-inflammatory mechanisms of gingerols may be related to inhibiting the production of inflammatory mediators and free radicals.
6 Anti-inflammatory effect of gingerols on inflammation induced by P. ternate agglutinin
The mouse peritonitis model induced by the agglutinin was applied to investigate the anti-inflammatory effects of gingerols by detecting the releases of inflammatory mediators PGE2 in the exudates. Toe swelling of rat induced by the agglutinin was used to determine the swelling extent. The result showed that gingerols exhibited comparable anti-inflammatory effects in terms of the inhibitions on the releases of inflammatory mediator(PGE2) and the swelling extent of rat
The research showed that raphides of P. ternate can cause intense inflammatory toxicity. Ginger juice and gingerols effectively antagonized to inflammatory induced by raphides of P. ternate. The anti-inflammatory mechanism of gingerols is not related to the release of adrenal cortex hormone by activating adrenocorticotropic hormone, and it may be an inhibition of COX-2, PGE2, TNF-a, NO, and MDA. The result also found that gingerols can inhibit the inflammatory effects induced by agglutinin. This paper clarified the scientific content on the theory of Chinese medicine "P. ternate can be detoxification by Ginger". It provided a basis to the clinical application of ginger detoxification to P. ternate.
半夏为天南星科植物半夏Pinellia ternata(Thunb.)Breit的块茎。自古以来,因其味辛辣、麻舌而刺喉,具有“戟人咽”的刺激性,被列为有毒中药。临床误服或使用不当,可致强烈的皮肤、粘膜接触性的刺激性毒性。本课题组前期研究表明半夏刺激性毒性成分为其含有的具有特殊晶型的“毒针晶”。半夏生品及毒针晶均可引起家兔眼结膜强烈水肿,使小鼠毛细管通透性增强,腹腔渗出液中炎症介质PGE2含量增加,其毒性表现与炎症效应极为相似。课题组进一步研究发现半夏毒针晶是主要由草酸钙、蛋白组成的复合物,其中蛋白含量为6.084%；毒针晶上带有凝集素蛋白,该蛋白能显著引起大鼠腹腔中性粒细胞向腹腔迁移和大鼠足趾肿胀。毒针晶中加入凝集素后,可显著加重炎症反应。这些结果表明半夏的刺激性毒性作用是由毒针晶的机械损伤加上凝集素蛋白的化学损伤双重作用产生。
中医临床上半夏中毒用生姜解毒。传统中医理论认为：“半夏性畏生姜,用之以制其毒,功益彰”。梁·陶弘景《本草经集注》中记载“半夏毒,用生姜汁,煮干姜汁并解之”。但生姜解半夏毒的机理不明。现代研究发现生姜具有抗炎镇痛、调节免疫等药理活性。而半夏毒针晶可引起强烈的炎症反应。故本学位论文提出假说“半夏的刺激性毒性在机体可表现为刺激性炎症毒性,生姜对半夏的解毒作用与其拮抗半夏所致的刺激性炎症毒性相关”。本学位论文据此设计了研究路线。
本学位论文采用多种炎症模型,以半夏毒针晶为致炎剂,发现半夏毒针晶可引起强烈的炎症毒性反应。研究表明生姜汁确实能显著拮抗半夏毒针晶所致的炎性作用,并筛选得出姜辣素类成分是生姜拮抗半夏毒针晶所致炎性反应的有效部位,其拮抗半夏所致炎症反应的机制不是通过兴奋肾上腺分泌肾上腺皮质激素而发挥作用,可能与抑制半夏毒针晶诱导的炎症介质的合成与释放有关。同时发现姜辣素类成分可拮抗半夏毒针晶中的主要化学刺激物(凝集素蛋白)的致炎效应。主要工作内容和研究结果包括以下几方面：
1半夏毒针晶的致炎作用研究
采用小鼠毛细管通透性试验、小鼠腹腔炎症试验及大鼠足趾肿胀试验,考察不同浓度半夏毒针晶所致的炎症毒性效应及其量-毒关系。研究结果表明：腹腔注射半夏毒针晶混悬液可使小鼠腹腔毛细血管通透性增加,腹腔渗出液中炎症介质PGE2含量增加,也可引起大鼠足趾肿胀,并在一定剂量范围内表现为典型的量-毒关系。此结果说明半夏毒针晶可诱导炎症,毒针晶的刺激性毒性在机体内主要表现为炎症反应。
2生姜汁对半夏毒针晶所致炎性反应的影响
采用半夏毒针晶所致小鼠腹腔炎症模型,观察生姜汁对小鼠毛细管通透性、腹腔渗出液中蛋白质含量、白细胞数量的影响；采用半夏毒针晶诱导大鼠足趾肿胀模型,观察生姜汁对半夏毒针晶所致大鼠足趾肿胀的影响。研究结果表明：生姜汁能显著抑制半夏毒针晶腹腔注射所致的小鼠毛细管通透性增加,减少腹腔渗出和白细胞数目,降低渗出液中蛋白质的含量,亦可减轻半夏毒针晶所致的大鼠足趾肿胀,说明生姜汁确实可拮抗半夏毒针晶所致的炎症反应,且其中高剂量组的拮抗效应与阳性药阿司匹林组相当。
3生姜各部位的提取及相关成分含量测定
生姜挥发油部位采用水蒸气蒸馏的方法提取,并采用气质联用法对其组分进行分析；生姜姜辣素部位为生姜经乙酸乙酯提取后去除挥发油后精制所得,并采用紫外分光光度法对姜辣素部位中总姜辣素含量进行测定,采用HPLC法对姜辣素部位中6-姜酚(6-gingerol)、6-姜烯酚(6-shogaol)进行含量测定；生姜乙酸乙酯提取后的药渣经水提取得到药渣水提物部位。结果获得挥发油、姜辣素、药渣水提物三个部位；生姜挥发油中共鉴定了64个化合物,主要为萜类物质；生姜姜辣素部位中总姜辣素含量为88.15%,6-姜酚和6-姜烯酚的含量分别为19.40%、8.11%。此结果说明姜辣素部位所含的总姜辣素含量较高,且生姜其他部位的提取方法亦可行,可作为生姜拮抗半夏毒针晶所致炎症的筛选部位。
4生姜各部位对半夏毒针晶所致炎性反应的影响
为筛选生姜中拮抗半夏毒针晶炎性反应的有效部位,采用腹腔注射半夏毒针晶所致小鼠腹腔炎症模型,观察生姜各提取部位对小鼠毛细管通透性、腹腔渗出液中蛋白质含量、白细胞数量的影响；采用半夏毒针晶诱导大鼠足趾肿胀模型,观察生姜各提取部位对大鼠足趾肿胀的作用。研究结果表明：姜辣素部位能显著抑制半夏毒针晶腹腔注射所致的小鼠毛细管通透性增加,降低蛋白质含量和白细胞数目,也可减轻半夏毒针晶所致的大鼠足趾肿胀,而挥发油及药渣水提物未见显著性影响。此结果表明生姜中的姜辣素类成分是拮抗半夏毒针晶所致炎症反应的有效部位。
5姜辣素类成分拮抗半夏毒针晶所致炎性反应机制的初步研究
为探讨姜辣素类成分的拮抗效应是否依赖于下丘脑-垂体-肾上腺皮质系统,采用半夏毒针晶诱导的正常大鼠和去肾上腺大鼠足趾肿胀试验,观察姜辣素类成分对正常大鼠和去肾上腺大鼠足趾肿胀的影响。对正常大鼠两侧肾上腺中胆固醇与VitC含量进行测定,观察姜辣素类成分对肾上腺中胆固醇与VitC含量的影响。同时采用半夏毒针晶诱导的小鼠腹腔炎症模型,观察姜辣素类成分对小鼠腹腔渗出液中PGE2、NO、MDA的影响;采用半夏毒针晶诱导的正常大鼠足趾肿胀模型,观察姜辣素类成分对大鼠炎足中COX-2、PGE2、TNF-α的影响。研究结果表明：姜辣素类成分可显著抑制半夏毒针晶所致的正常大鼠足趾肿胀和去肾上腺大鼠足趾肿胀,且对正常大鼠肾上腺中胆固醇和VitC的合成释放无显著影响,表明姜辣素类成分拮抗半夏毒针晶所致炎性反应不是通过兴奋肾上腺分泌肾上腺皮质激素而发挥作用的。同时,姜辣素类成分可抑制半夏毒针晶所致的小鼠腹腔渗出液中PGE2、NO、MDA的生成,还能显著抑制半夏毒针晶所致大鼠炎足中COX-2、PGE2、TNF-α的生成,提示可能与抑制COX-2、PGE2、TNF-α、NO、MDA的生成有关。
6姜辣素类成分对半夏凝集素所致炎性反应的影响
课题组前期研究表明凝集素蛋白是半夏毒针晶中的主要蛋白,可以引起大鼠腹腔白细胞迁移、渗出液中PGE2含量增加和大鼠足趾肿胀,是半夏毒针晶中引起炎症刺激的主要化学物质。故将提取所得的凝集素作为致炎剂,采用小鼠腹腔炎症模型和大鼠足趾肿胀模型,考察姜辣素类成分对半夏凝集素所致炎症反应的影响。结果显示半夏凝集素可显著引起小鼠腹腔渗出液中PGE2含量增高及大鼠足趾肿胀,并可加重毒针晶的致炎作用；姜辣素类成分可显著抑制半夏凝集素所致的炎症反应,亦可拮抗半夏凝集素与毒针晶协同所致的炎症反应。
通过上述研究表明,半夏毒针晶可引起机体强烈的刺激性炎症毒性,而生姜汁及生姜中的姜辣素类成分能有效拮抗半夏毒针晶所致的炎性反应,并初步阐明姜辣素类成分拮抗半夏毒针晶炎性反应不依赖于肾上腺分泌肾上腺皮质激素系统,其机制可能与抑制毒针晶诱导的炎症因子有关。同时研究进一步证明半夏凝集素是半夏毒针晶中的主要化学刺激物,姜辣素类成分可拮抗半夏凝集素所致的炎性反应。说明生姜确实可以起到解半夏毒的作用,其作用机制是生姜中的姜辣素类成分可直接拮抗半夏毒针晶刺激后产生的炎症反应,减轻毒针晶上的凝集素蛋白所产生的炎症反应。
本学位论文对“生姜解半夏毒”的传统中医理论进行了探索性研究,结果揭示了何为半夏毒,生姜中解半夏毒的成分,并初步揭示了生姜的解毒机制,证实此传统中医理论的科学性,为临床半夏中毒的解毒提供理论基础。本学位论文的研究可为中医理论的现代科学内涵研究提供了较好的借鉴作用。
This project was supported by national natural science foundation (No.30772785, NO. 30973939), "Eleven-Five" national projects of technological supporting (No.2006BAI09B06-10).
Pinellia ternata (Thunb.) Breit. whose tuberous stems are important Chinese medicines, is taxonomically belonged to Araceae family, and are well known for their irritant properties. If chewed and touched raw, the corms of the plants could result in swelling and burning pain in the mucous membranes, and an unbearable itching in skin. The needle-like raphides of calcium oxalate were proved to be their common poisonous components, named as toxic raphides. The raphides caused severe conjunctival edema in rabbit, increased capillary permeability and content of PGE2 in the exudates in mice. Toxic raphide were a complex compsed by mainly calcium oxalate crystals and protein. The content of protein was 6.084%. The study found that the agglutinin on the toxic raphide can significantly induce rat peritoneal neutrophil migration to peritoneal and rat paw edema. These results indicated that the reason of the toxic effects of raphides were the dual role of mechanical damage by calcium oxalate and chemical inflammation induced by agglutinin.
Ginger was used to detoxificate to P. ternate in clinic. Traditional Chinese medicine theory held that "P. ternata feared ginger, and cooked with ginger for detoxification". Tao Hongjing held that "P. ternata was toxic and was detoxificated by ginger juice and dry ginger" However, the mechanism of ginger detoxification to P. ternata was unknown. Modern research showed that ginger had anti-inflammatory, analgesic, immune and other pharmacological activity. This paper was put forward the hypothesis "the irritating toxic of P. ternata in the body can be expressed as an inflammation. Ginger detoxification of P. ternata was related to the antagonistic effect of inflammation caused by P. ternata". This paper was designed according to this line of the research hypothesis.
Inflammation models were used to reseach the raphides. The result found that raphides can cause irritant toxicity, and ginger juice can really antagonize to inflammation induced by the raphides. Gingerols were an effective part of ginger which did not depend on the anti-inflammatory mechanisms of the release of adrenal cortex hormone by activating adrenocorticotropic hormone, and its anti-inflammatory mechanism may be an inhibition of inflammatory mediators induced by the raphides in P. ternate. The result also found that gingerols can inhibit the inflammatory effects caused by P. ternate agglutinin. Main contents and findings were the following:
1. The inflammatory effect induced by raphides in P. ternate
The mouse capillary permeability test, mouse peritonitis and toe swelling of rat induced by the raphides were applied to investigate the inflammatory effects of different concentrations of raphides. The result showed that raphides can increase the capillary permeability, caused the release of inflammatory mediator (PGE2) and toe swelling of rat.
2 Anti-inflammatory effect of ginger juice on inflammation induced by raphides in P. ternate
The mouse peritonitis model induced by the raphides was applied to investigate the anti-inflammatory effects of ginger juice by detecting the capillary permeability, quantity of leukocytes, and the protein content in the exudates. Toe swelling of rat induced by the raphides was used to determine the swelling extent. The result showed that ginger juice exhibited comparable anti-inflammatory effects in terms of the inhibitions on the exudation and leukocytes efflux, and the production of protein. Ginger juice inhibited penetration of capillary vessel in mouse and toe swelling of rat induced by the raphides.
3 Three extracts of ginger and component analysis
Ginger volatile oils, extracted by steam distillation, were analyzed by GC/MS. Gingerols were obtained from ginger which was extracted by ethyl acetate and was removed of volatile oils. The content of total gingerols was determined by UV spectrophotometry. The content of 6-gingeroland 6-shogaol was determined by HPLC. After extracted by the ethyl acetate, ginger dregs were extracted again by water, called as aqueous extract. The result showed that ginger volatile oil, gingerols, and aqueous extract of ginger were obtained. GC/MS analysis showed that there were 64 compounds in volatile oil which were identified mainly terpenoids. The content of total gingerols,6-gingerol, and 6-shogaol were 88.15%,19.40%and 8.11%, respectively. The results were ready to screen the active part from three extracts further.
4 Anti-inflammatory effect of three parts of ginger extract on inflammation induced by raphides in P. ternate
The mouse peritonitis model induced by the raphides induced was applied to investigate the anti-inflammatory effects of three ginger extracts by detecting the capillary permeability, quantity of leukocytes, and the protein content in the exudates. Toe swelling of rat induced by the raphides was used to determine the swelling extent. The result showed that gingerols exhibited comparable anti-inflammatory effects in terms of the inhibitions on the exudation and leukocytes efflux, and the production of protein. Gingerols inhibited penetration of capillary vessel in mouse and toe swelling of rat induced by the raphides. The volatile oils and aqueous extract did not have the anti-inflammatory effects.
5 Anti-inflammatory mechanisms of gingerols related to inhibiting inflammatory by raphides in P. ternate
According to the results of previous studies, toe swelling induced by the raphides of normal rat and toe swelling induced by the raphides of bilaterally adrenalectomized rats were used to determine the swelling extent. The contents of VitC and cholesterol were measured in normal adrenal glands. The result showed that gingerols had a significantly suppressive effect on paw edema of normal rat and adrenalectomized rat induced by raphides and had no effect on the contents of VitC and cholesterol in normal adrenal glands. The result showed gingerols had an anti-inflammatory effect, which were independent on pituitary-adrenal axis.
The content of PGE2, NO and MDA in the mouse exudate were respectively measured in rats with acute peritonitis induced by raphides. The activity of COX-2 and the content such as PGE2, TNF-a were examined in the toe of rats induced by raphides. The result showed that gingerols significantly inhibited the production of NO, PGE2, and MDA in exudate of peritonitis rats. Furthermore, gingerols inhibited the activity of COX-2, and reduced the production of PGE2 and TNF-a in the toe. The anti-inflammatory mechanisms of gingerols may be related to inhibiting the production of inflammatory mediators and free radicals.
6 Anti-inflammatory effect of gingerols on inflammation induced by P. ternate agglutinin
The mouse peritonitis model induced by the agglutinin was applied to investigate the anti-inflammatory effects of gingerols by detecting the releases of inflammatory mediators PGE2 in the exudates. Toe swelling of rat induced by the agglutinin was used to determine the swelling extent. The result showed that gingerols exhibited comparable anti-inflammatory effects in terms of the inhibitions on the releases of inflammatory mediator(PGE2) and the swelling extent of rat
The research showed that raphides of P. ternate can cause intense inflammatory toxicity. Ginger juice and gingerols effectively antagonized to inflammatory induced by raphides of P. ternate. The anti-inflammatory mechanism of gingerols is not related to the release of adrenal cortex hormone by activating adrenocorticotropic hormone, and it may be an inhibition of COX-2, PGE2, TNF-a, NO, and MDA. The result also found that gingerols can inhibit the inflammatory effects induced by agglutinin. This paper clarified the scientific content on the theory of Chinese medicine "P. ternate can be detoxification by Ginger". It provided a basis to the clinical application of ginger detoxification to P. ternate.
引文
[1]修彦凤,王智华,洪筱坤.半夏毒性的研究进展[J].时珍国医国药,2004,15(5)：304-305.
[2]吴仪洛.本草从新[M].上海：上海科技出版社,1958.103.
[3]陶弘景,尚志钧辑校.本草经集注[M].芜湖：皖南医学院科研科印,1985：49.
[4]贾俊斌,田海生.误食生半夏中毒11例报道[J].中国乡村医生杂志,1999,15(3)：44.
[5]中医研究院中药研究所药理室、生药室炮制组.半夏炮制的毒性研究[J].新医药学杂志,1979,(7)：38-40
[6]罗国亮.半夏的毒性及临床应用[J].中草药,1999(2)：156.
[7]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421.[8]Seet B, Chan WK, Ang CL. Crystalline keratopathy from Dieffenbachia plant sap[J]. Br J Ophthalmol,1995,79: 98-99.
[9]Drach G, Maloney W. Toxicity of common houseplant Dieffebachia[J]. JAMA,1963,184:1047-1048.
[10]Lin TJ, Hung DZ, Hu WH, et al. Calcium oxalate is the main toxic component in clinical presentations of alocasis macrorrhiza (L) Schott and Endl poisonings[J]. Vet Hum Toxicol,1998,40(2):93-98.
[11]Hsueh KF, Lin PU, Lee SM, et al. Ocular injuries from plant sap of genera euphorbia and Dieffenbachia[J]. J ChinMed Assoc,2004,67:93.
[12]Van Ketel, Bruynzeel DP.Contact dermatitis to plants in Amsterdam[J]. Boll Dermatol Allergol Profess, 1987,2:132-144.
[13]吴皓,李伟,韩洪涛,等.半夏刺激性成分的研究[J].中国中药杂志,1999,24(12)：725-730.
[14]钟凌云,吴皓,张科卫,等.生半夏中草酸钙针晶的刺激性作用研究[J].中国中药杂志,2006,31(20)：1706-1710.
[15]葛秀云,吴皓.天南星科有毒中药毒针晶的组成成分分析[J].药物分析,2010,30(2)：190-193.
[16]吴皓,郁红礼,史闰均,等.凝集素：半夏及掌叶半夏毒针晶中的化学刺激性毒性成分[J].中药炮制技术、学术交流暨产业发展高峰论坛,2010,161-173.
[17]Ali BH, Blunden G, Tanira MO, et al. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe):A review of recent research[J]. Food and Chemical Toxicology, 2008,46:409-420.
[18]卢传坚,欧明,王宁生.姜的化学成分分析研究概述[J].中药新药与临床药理,2003,14(3)：215-217.
[19]李计萍,王跃生,马华,等.干姜与生姜主要化学成分的比较研究[J],中国中药杂志,2001,26(11)：748-751
[20]李海宁.生姜的抗动脉粥样硬化作用[J],国外医学.卫生学分册,2003,30(2)：98-101.
[21]张相年.姜精油的研究进展[J],广州化学,1992,(2)：65.
[22]李铁纯,回瑞华,侯冬岩,等.生姜挥发性成分的分析,分析科学学报,2003,19(5)：447-448.
[23]崔庆新,董岩.生姜挥发油化学成分的GC-MS分析研究,2006,19(2)：43-45.
[24]吴贾锋,张诚,张晓鸣,等.生姜风味物质的提取和成分分析[J].食品与机械,2006,23(3)：94-99.
[25]孙亚青,李景明,李丽梅.姜精油的Gc Ms分析研究[J].食品与发酵工业,2004,30(6)：95-99.
[26]D.W. Connell, R. McLachlan. Natural pungent compounds:Ⅳ. Examination of the gingerols, shogaols, paradols and related compounds by thin-layer and gas chromatography[J]. Journal of Chromatography A.1972, 67(1):29-35.
[27]王发松,胡海燕,黄世亮,等.姜油的分子蒸馏纯化与化学成分分析,中国医药工业杂志,2003,34(3)：125-127
[28]张维勒·姜辣素的测定方法[J].山东农业科学,1991(6)：11-14.
[29]黄雪松,王汉忠.姜辣素的测定方法[J]·中国调味品,1996(8)：30-31.
[30]杨春海,易杨慧,余爱农.溶出伏安法测定姜中姜辣素含量的研究,食品科学,2003,24(2)：110-112.
[31]张明昶,李健,蒙继昭.紫外分光光度法测定姜中姜辣素类化合物的含量[J].贵州医药,2003,27(3)：283-284.
[32]李凤华,张利民,孙淑华,等.生姜中姜辣素的提取及测定的研究[J].东北农业大学学报,2007,38(6)：746-749.
[33]王维皓,王智民,徐丽珍,等HPLC法测定生姜中有效成分6-姜辣素的含量[J].中国中药杂志,2002,27(5)：348-349.
[34]马雯雯,何前松,张永萍,等.高效液相色谱法测定生姜中6-姜酚的含量[J].微量元素与健康研究,2009, 26(6)：27-28.
[35]黄雪松,汪建民,王兆升.干姜、姜皮、泡姜中辣味成分的HPLC测定[J].中草药,1999,30(6)：423-424.
[36]陈燕,蔡同一,付力,等.用改进的高效液相色谱法(HPLC)测定姜中姜辣素[J].食品科学,2000,22(4)：60-63.
[37]张科卫,宋申,崔小兵,等.全国主要产区生姜中6-姜酚、6-姜醇含量的测定[J].中国药学杂志,2009,44(22)：1692-1694.
[38]Xian—Guo He. High performance Liquid chromatograph Electlo Spray Mass Spectrometric Analysis of Pungent Constituents of Ginger[J]. Journal of Chromatography A,1998,796(2):327.
[39]Kikuzaki H. Antioxidant effects of some ginger constituents[J]. J Food, Sci,1993,58(6):1407.
[40]Kikuzaki H, Kobayashi M, Nakatani N. Diarylheptanoids from rhizomes of zingiber ofeinale[J]. Phytochemistry,1991,30(11):3647-3651.
[41]Kikuzaki H, Nakatani N. Cyclic diaryl heptanoids from rhimmes of zingiber offeinale[J]. Phytochemistry, 1996,43(1):273-277.
[42]何文珊,李琳,李炎,等.生姜中一种新化合物的抗氧化活性[J].中国病理生理杂志,2002,17(5)：461.
[43]Jianping Ma, Xiaoling Jin, Li Yang, eta. Diarylheptanoids from the rhizomes of Zingiber officinale[J]. Phytochemistry,2004,65(8):1137-1143.
[44]Kiuchi F., Shibuya M., Sankawa U.. Inhibitors of prostaglandin biosynthesis from ginger[J]. Chem. Pharm. Bull,1982,30:754-757.
[45]Flynn D.L., Rafferty M.F., Boctor A.M.. Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds[J]. Prostaglandins Leukot Med,1986,24(2-3): 195-198.
[46]Charlier, C., Michaux, C. Dual inhibition of cyclooxygenase-2(COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs[J]. Eur. J. Med. Chem.,2003,38(7-8): 645-659.
[47]Grzanna R., Lindmark L., Frondoza C.G. Ginger-an herbal medicinal product with broad anti-inflammatory actions[J]. Journal of Medicinal Food,2005,8:125-132.
[48]Grzanna R., Phan P., Polotsky A., Lindmark L.,et al. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes[J]. J. Altern. Complement. Med.,2004,10: 1009-1013.
[49]Lantz R.C., Chen G.J., Sarihan M., et al. The effect of extracts from ginger rhizome on inflammatory mediator production[J]. Phytomedicine,2007,14:123-128.
[50]Mascolo N., Jain R., Jain S.C., et al. Ethnopharmacologic investigation of ginger (Zingibero□cinale)[J]. J. Ethnopharmacol.,1989,27,129-140.
[51]Kiuchi F., Iwakami S., Shibuya M., et al. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids[J]. Chem. Pharm. Bull.,1992,40:387-391.
[52]Young H.Y., Luo Y.L., Cheng H.Y., et al. Analgesic and anti-inflammatory activities of [6]-gingerol[J]. Journal of Ethnopharmacology,2005,96(1-2),207-210.
[53]Tripathi S., Maier K.G., Bruch D., et al. Effect of 6-Gingerol on Pro-Inflammatory Cytokine Production and Costimulatory Molecule Expression in Murine Peritoneal Macrophages[J]. Journal of Surgical Research, 2007,138(2):209-213.[54] Nurtjahja-Tjendraputra E., Ammit A.J., et al. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger[J]. Thromb. Res.,2003,111(4-5):259-265.[55] Dedov V.N., Tran V.H., Duke C.C., et al. Gingerols:a novel class of vanilloid receptor (VR1) agonists[J]. Br. J. Pharmacol.,2002,137(6):793-798.
[56]何文珊,魏孝义,李琳,等.生姜中一新的抗氧化二苯基环氧庚烷成分[J].植物学报,2001,43(7)：757-759.
[57]Masuda Y.,Kikuzaki H,Hisamot M,Nakatan N.Antioxidant properties of gingerol related compounds from ginger.BioFactors,2004,21(1-4):293-296.
[58]Katsunari Ippoushi, Atsuko Takeuchi, Hidekazu Ito,etal. Antioxidative effects of daikon sprout (Raphanus sativus L.) and ginger (Zingiber officinale Roscoe) in rats[J]. Food Chemistry.2007,102:237-242.
[59]I. Stoilova, A. Krastanov, A. Stoyanova, etal. Antioxidant activity of a ginger extract (Zingiber officinale)[J]. Food Chemistry,2007,102(3):764-770.
[60]杨雷香,周长新,黄可新,等.生姜中二苯庚烷类化合物的抗氧化[J].中国中药杂志,2009,34(3)：319-323.
[61]张霖,吴庆琛,张诚.生姜醇提取物对人肺腺癌细胞(A549)增殖和凋亡的影响[J].中国药房,2010,21(39)：3656-3658.
[62]Park K.K., Chun K.S., Lee J.M.,etal.. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett.1998,129:139-144.
[63]Liu H., Zhu Y.. Effect of alcohol extract of Zingiber officinale Rosc on immunologic function of mice with Tumor[J]. Wei Sheng Yan Jiu,2002,31(3):208-209.
[64]熊平源,马丙娜,郭明雄.生姜对小鼠免疫功能影响的实验研究[J],数理医药学杂志,2006,19(3)：243-244.
[65]李景舜,赵淑华,王春华,等.生姜提取物对X射线损伤免疫功能拮抗作用[J].中国公共卫生,2006,(2)：171-172.
[66]Mahady G B,Pendland S L.Ginger and the gingerols inhibit the growth of CagA+strains of Helicobater pylori. Anticancer Res.2003,23(5A):3699-3702.
[67]Thongson C, Davidson P M. Antimicrobial effect of Thai spices against listeria monocytogenes and Salmonella typhimurium DT104. J Food Prot,2005,68(10):2054-2058.
[68]刘瑜,张卫明,单承莺,等.生姜挥发油抑菌活性研究[J].食品工业科技,2008,(3)：88-90.
[69]姜正林,沈洪妹,杨凯.生姜与抗胆碱药的抗大鼠模拟运动病作用的比较观察[J].中华航海医学杂志, 1999,6(1)：20-22
[70]Willetts KE, Ekangaki A, Eden J A. Effect of a ginger extract on pregnancy-induced nausea:A randomised controlled trial[J]. Australian and New Zealand Journal of Obstetrics and Gynaecology.2003, 43(2):139-144
[71]Stripramote M, Lekhyananda N. A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy [J]. J Med Assoc Thai,2003,86(9):846-853.
[72]Sharma S S,Gupta Y K. Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale)[J]. Journal of ethnopharmacology,1998,62(1):49-55.
[73]赵德雪,杨志宏,李明,等.生姜对呕吐模型水貂止呕作用的研究[J],中国药事,2006,20(10)：601-104.
[74]卢传坚,欧明,王宁生.姜对心脑血管系统的药理作用[J].中药新药与临床药理.2003,14(5)：356-360.
[75]张明发,苏晓玲,沈雅琴.干姜现代药理研究概述[J].中国中医药科技.1996,3(2)：46.
[76]张竹心,刘连生.生姜油的抗过敏作用[J].中成药,1992,14(11)：30-31.
[77]Fuhrman B, Rosenbat M, Hayek T, et al. Ginger extract consumption reduced plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E3/deficient mice. J Nutr,2000,130(5):1124-1131.
[78]陈燕,田泽,葛毅强,等.姜油树脂调节血脂和抗血小板聚集作用的研究.营养学报,2001,23(4)：338-341.
[79]龚庆宣.刘涓子鬼遗方[M].北京：人民卫生出版社影印,1956.15.
[80]张在其.急性生半夏中毒14例临床分析[J].中国乡村医生杂志,2000,(6)：38.
[81]邵月如,夏俐俐.生半夏中毒及其解救[J].时珍国医国药,2000,11(8)：754.[82]Aniijima, Mkubo, Khashimoto, et al. Effect of oral administration of Pinellia ternata Zingiber rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve in the rat [J]. Neuroscience Letters,1998,258(1):5-8.
[83]吴皓,蔡宝昌,史小良,等.半夏姜制对动物刺激性及毒性的影响[J].中国中药杂志,1993,18(7)：408-410
[84]王金华,薛宝云.生姜与干姜药理活性的比较研究[J].中国药学杂志,2000,35(3)：163-165.
[85]吴皓,舒武琴,邱鲁婴,等.生姜解半夏毒的实验研究[J].中药材,1998,21(3)：137-140.
[86]吴皓,陆跃鸣,孙黎清,等.姜汁用量对姜浸半夏炮制品的影响[J].中药材,1998,21(6)：291-294
[87]魏伟,李晓辉,张洪泉,等.抗炎免疫药理学[M].2005,1：10-11.[88]吴皓,钟凌云,李伟,等.半夏炮制解毒机制的研究Ⅰ[J].中国中药杂志,2007,32(14)：1402-1405
[1]洪美玲主编.病理学[M].人民卫生出版社,1999：50.
[2]杨光华主编.病理学[M].第五版,人民卫生出版社.2001：57.
[3]王晓良.应用分子药理学[M].北京：中国协和医科大学出版社,2005：297-306.
[4]吴雪,秦明放.重症腹膜炎的致炎细胞因子研究进展[J].中国中西医结合外科杂志,2000,2(1)：61-63.
[5]Alam R. Chemokines in allergic inflammation[J]. J Allergy Clin Immumal.1997,99:273-277.
[6]杨卫红等.黏附分子与炎症.国外医学免疫分册[J].1999,22(1)：14-16.
[7]苏静怡.细胞粘附的生理与病理生理生理科学进展[J].1996,27(4)：374-382.
[8]Bredt D S, Snyder S H. Nitric Oxide as a neuronal messenger[J]. Trends PharmacolSci.1991,12(4): 125-128.
[9]李玉林.《分子病理学》[M].第一版,人民卫生出版社,2002：210-239.
[10]郭双平,翟宇强.核转录因子NF-κB的研究进展[J].中华病理学杂志.2000,29(5)：379-380
[11]杨刚.内分泌生理与病理生理学[M].第二版,天津科学技术出版社,1996,60-64
[12]张宏,彭成.附子抗免疫佐剂性关节炎的蛋白质组学研究[J].中华实用中西医杂志.2005,18(22)：1567-1569
[13]谢世荣,黄彩云,黄胜英.山豆根碱抗炎作用的研究[J].中草药.2003,34(4)：355-357
[14]鄢顺琴,凤良元,丁荣光.金钱白花蛇抗炎作用的实验研究[J].中药材,1994,17(12)：29-30.
[15]沈映君.中药“辛”味、挥发油、表证与炎症的关系[J].四川生理科学杂志,2004,26(4)：163
[16]赵璐,曾南.环氧化酶-2与中药抗炎作用的关系[J].中华中医药学刊,2008,26(1)：102-103.
[17]刘少平,董卫国,吴东方,等.阿魏酸钠对结肠炎大鼠结肠组织一氧化氮合酶和环氧合酶的影响[J].中国药理学通报,2003,19(5)：571-574.
[18]简燕婷,王继德,麦国丰,等.姜黄素对肠炎大鼠肠黏膜环氧合酶-2的调控[J].第四军医大学学报,2005,26(6)：521-524.
[19]黄秋菊,季晖,赖宜生,等.ZLJ-601抗炎作用及其机制研究[J].中国药科大学学报2008,39(4)：333-337
[20]刘芳,曲极冰,李红角,等.白藜芦醇抗炎作用机制的初步研究[J].中国药学杂志,2006,41(15)：1138-1141.
[21]王玮,白月,王俊平,等.黄芩茎叶总黄酮对大鼠气囊滑膜炎抗炎作用机制的研究[J].临床与用药,2009,26(4)：460.
[22]俊艳宁,朱秀坦,程桂芳.黄芩甙的抗炎机理[J].药理学报,2000,35(3)：161-164.
[23]覃仁安,梅璇,陈敏,等.鹅不食草挥发油抗炎作用及机制研究[J].2006,26(4)：369-371.
[24]崔晓燕,王素霞,候永利.金银花提取物的抗炎机制研究[J].中国药房,2007,18(24)：1861-1863.
[25]佟继铭,赵波,张玉玲.赤雹果水提物对佐剂性关节炎大鼠抗炎作用及机制研究[J].承德医学院学报,2010,27(4)：348-351.
[26]魏安祥,杨士友,阚红卫,等.柴黄复方颗粒抗炎镇痛作用及机制研究[J].中国实验方剂学杂志,2009,15(10)：82-84.
[27]肖振宇,张俊平,陆峰,等.商陆皂苷甲对细胞间粘附的影响[J].药学学报,2003,38(10)：728-730.
[28]郝钰,邱全瑛,吴珺,等.小檗碱对IL-1或TNF诱导的多形核白细胞与内皮细胞粘附的影响[J].中国病理生理杂志,2000,16(7)：585-58.
[29]唐旭东,姜建青,姜大春,等.三七总皂苷对心肌缺血在灌注中中性粒细胞核因子一KB活化及其粘附的影响.中国药理学通报,2002,18(5)：556-560.
[30]庞然,张淑玲,赵雷,等.蛇莓乙醇提取物的体外抗炎机制研究[J].华中科技大学学报(医学版),2009,38(4)：481-485.
[31]马涛,曹颖林,李欢,等.布洛芬川芎嗪酯的抗炎机制[J].沈阳药科大学学报,2005,22(4)：291-294.
[32]任俊,党月兰,李淑玉.红毛五加总甙抗炎机制研究[J].中药药理与临床,2002,18(6)：13-14.
[33]李淑慧,李晓辉,楚延.三七总皂苷抗炎作用机制的实验研究[J].中草药,2001,31(9)：676-678.
[34]李明春,雷林生,梁东升,等.灵芝多糖对小鼠腹腔巨噬细胞活性氧自由基的影响[J].中国药理学与毒理学杂志,2000,14(1)：65-68.
[35]宋媛嫒,李嫒,张洪泉.丁香苷抗炎镇痛作用及部分机制研究[J].中国野生植物资源,2010,29(4)：28-30.
[36]李文广,张小郁,吴勇杰,等.草血竭提取物抗炎作用和机制研究[J].中药药理与临床,2002,18(2)：18-20.
[37]张黎,陈志武,王瑜,等.银杏叶总黄酮抗炎作用及机制探讨[J].安徽医科大学学报,2001,36(5)：350-352
[38]姚余有,江礼生,陈敏珠.黄芪总黄酮对大鼠佐剂性关节炎的治疗作用及机制研究[J].中成药,2001,23(9)：661-663
[39]张骏,翁福海,李会强,等.大黄素对大鼠腹腔巨噬细胞产生TNF-α, IL-1, IL-6以及细胞内钙离子的影响[J].中草药,2001,32(8)：718-721.
[1]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421.
[2]中医研究院中药研究所药理室、生药室炮制组.半夏炮制的毒性研究[J].新医药杂志,1997,(7)：38-40.
[3]罗国亮.半夏的毒性及临床应用[J].中草药,1999,(2)：156.
[4]吴皓,李伟,韩洪涛,等.半夏刺激性成分的研究[J].中国中药杂志,1999,24(12)：725-730.
[5]钟凌云,吴皓,张科卫,等.生半夏中草酸钙针晶的刺激性作用研究[J].中国中药杂志,2006,31(20)：1706-1710.
[6]Seet B, Chan W.K., Ang C.L.. Crystalline keratopathy from Dieffenbachia plant sap[J]. Br J Ophthalmol, 1995,79:98-99.
[7]Lin T. J., Hung D. Z., Hu W. H., et al. Calcium oxalate is the main toxic component in clinical presentations of alocasis macrorrhiza (L) Schott and Endl poisonings[J]. Vet Hum Toxicol,1998,40(2):93-98.
[8]Hsueh K. F., Lin P. U., Lee S. M., et al. Ocular injuries from plant sap of genera euphorbia and Dieffenbachia[J]. J ChinMed Assoc,2004,67:93.
[9]陈奇.中药药理研究方法学[M].北京：人民卫生出版社,1996.306,364.
[10]黄秋菊,季晖,赖宜生.ZLJ2601抗炎作用及其机制研究[J].中国药科大学学报.2008,34(4)：333-337.
[11]魏伟,李晓辉,张洪泉,等.抗炎免疫药理学[M].2005,1,10-11.
[1]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421
[2]吴皓,李伟,韩洪涛,等.半夏刺激性成分的研究[J].中国中药杂志,1999,24(12)：725-730
[3]钟凌云,吴皓,张科卫,等.生半夏中草酸钙针晶的刺激性作用研究[J].中国中药杂志,2006,31(20)：1706-1710
[4]吴仪洛.本草丛新[M].上海科技出版社.1958：103
[5]陶弘景,尚志钧辑校.本草经集注[M].皖南医学院科研科印.1985：49
[6]张在其.急性生半夏中毒14例临床分析[J].中国乡村医生杂志,2000,(6)：38.
[7]邵月如,夏俐俐.生半夏中毒及其解救[J].时珍国医国药,2000,11(8)：754.
[8]Kiuchi F., Shibuya M., Sankawa U.. Inhibitors of prostaglandin biosynthesis from ginger[J]. Chem. Pharm. Bull,1982,30:754-757
[9]Grzanna R., Phan P., Polotsky A., Lindmark L.,et al. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes[J]. J. Altern. Complement. Med.,2004,10: 1009-1013
[10]Mascolo N., Jain R., Jain S.C., et al. Ethnopharmacologic investigation of ginger (Zingiber offcinale) [J]. J. Ethnopharmacol.,1989,27:129-140
[11]陈奇.中药药理研究方法学[M].人民卫生出版社.1996：306,364
[12]黄秋菊,季晖,赖宜生.ZLJ2601抗炎作用及其机制研究[J].中国药科大学学报.2008,34(4)：333-337
[13]Lantz R.C., Chen G.J., Sarihan M., et al. The effect of extracts from ginger rhizome on inflammatory mediator production[J]. Phytomedicine,2007,14:123-128.
[14]Mascolo N., Jain R., Jain S.C., et al. Ethnopharmacologic investigation of ginger (Zingibero□cinale)[J]. J. Ethnopharmacol.,1989,27,129-140.
[15]Young H.Y., Luo Y.L., Cheng H.Y., et al. Analgesic and anti-inflammatory activities of [6]-gingerol[J]. Journal of Ethnopharmacology,2005,96(1-2),207-210.
[1]卢传坚,欧明,王宁生.姜的化学成分分析研究概述[J].中药新药与临床药理,2003,14(3)：215-217.
[2]黄雪松,宴日安,吴建中.姜酚的生物活性述评[J].暨南大学学报(自然科学版),2005,26(3)：436-439.
[3]张雪红,李华昌.姜辣素的研究进展[J].矿冶,2003,12(4)：96-98.
[4]严赞开.姜酚的提取及抗氧化性试验[J].安徽农业科学.2006,34(4)：607,610.
[5]姜子涛,李荣.姜辣素化学及其研究进展[J].食品研究与开发,1998,19(1)：7-10.
[6]刘伟,刘成梅,李明,等.超声波萃取姜辣素工艺研究[J].中成药.2007,29(7)：1071-1073.
[7]唐仕荣,宋慧,刘全德,等.超声波-微波协同萃取姜辣素的工艺研究[J].食品与机械.2008,24(6)：76-79.
[8]田迪英,杨荣华.微波辐射对生姜抗氧化活性物质的浸提作用[J].国调味品,2006,(12)：17-21.
[1]刘瑜,张卫明,单承莺,等.生姜挥发油抑菌活性研究[J].食品工业科技,2008,(3),88-90
[2]王军,刘惠霞,张薇,等.生姜挥发油对脑缺血再灌注损伤的保护作用[J].2007,48(7)：644-646
[3]殷银霞,蔺兴遥.生姜挥发油的镇痛作用及其对胃溃疡大鼠血清中吲哚类神经递质的影响[J].卫生职业教育,2007,25(11)：142-143
[1]H.Y. Young, Y.L. Luo, H.Y. Cheng, etc. Analgesic and anti-inflammatory activities of [6]-gingerol[J]. Journal of Ethnopharmacology,2005,96:207-210
[2]黄雪松,宴日安,吴建中.姜酚的生物活性述评[J].暨南大学学报(自然科学版),2005,26(3)：436-439.
[3]S. Chrubasik, M.H. Pittler, B.D. Roufogalis. Zingiberis rhizoma:A comprehensive review on the ginger effect and efficacy profile[J]. Phytomedicine,2005,12:684-701
[4]张维勤.姜辣素的测定方法[J].山东农业科学,1999,(6)：11-14.
[5]黄雪松,王汉忠.姜辣素的测定方法[J].中国调味品,1996,(8)：30-32.
[6]郭晓斐,杜爱琴,杜爱玲.生姜中姜辣素含量的测定[J].山东化工,2007,36：34-37.
[7]张明昶,李健,蒙继昭.紫外分光光度法测定姜中姜辣素类化合物的含量[J].贵州医药2003,27(3)：283-284.
[8]李凤华,张利民,孙淑华,等.生姜中姜辣素的提取及测定的研究[J].东北农业大学学报,2007,38(6)：746-749.
[1]陈奇.中药药理研究方法学[M].人民卫生出版社.1996：306,364
[2]黄秋菊,季晖,赖宜生.ZLJ2601抗炎作用及其机制研究[J].中国药科大学学报.2008；34(4)：333-337
[1]梁鸿,赵玉英,李德宇,等.柴胡属植物化学成分及药理活性研究进展[J].国外医药·植物药分册,1999,14(5)：191.
[2]张宏,彭成.附子抗免疫佐剂性关节炎的蛋白质组学研究[J].中华实用中西医杂志.2005,18(22)：1567-1569
[3]陈万生,韩军,李力,等.知母总多糖的抗炎作用[J].第二军医大学学报,1999,20(10)：758.
[4]谢世荣,黄彩云,黄胜英.山豆根碱抗炎作用的研究[J].中草药.2003,34(4)：355-357.
[5]李仪奎.中药药理实验方法学[M].上海：上海科学技术出版社,1991：300.233-234.
[6]徐叔云,卞如濂,陈修.药理实验方法学,第三版[M].北京人民卫生出版社,2001：911-912,929-930.
[7]杨刚.内分泌生理与病理生理学[M].第二版,天津科学技术出版社,1996：60-64
[1]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421.
[2]Grzanna R, Phan P, Polotsky A, Lindmark L,et al. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes[J]. J. Altern. Complement. Med.,2004,10: 1009-1013.
[3]Kiuchi F, Iwakami S, Shibuya M, et al. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids[J]. Chem. Pharm. Bull.,1992,40:387-391.
[4]Tripathi S, Maier KG, Bruch D, et al. Effect of 6-Gingerol on Pro-Inflammatory Cytokine Production and Costimulatory Molecule Expression in Murine Peritoneal Macrophages[J]. Journal of Surgical Research,2007, 138(2):209-213.
[5]杨世杰主编.药理学[M].人民卫生出版社,2001,421
[6]周武庆.一氧化氮在炎症和免疫调节中的作用[J].国外医学皮肤性病学分册.1999,25(4)：233-235.
[7]Moncada S, Palmer RM. Inhibition of the induction of nitric oxide synthase by glucocorticoids:yet another explanation for their anti-inflammatory effects?[J]. TrendsPharmacolSei.1991,12(4):130-131
[8]Snyder S H, Bredt D S. Nitric oxide as a neuronal messenger[J]. Trends Pharmacol Sci.1991,12(4): 125-128.
[9]Clancy R M, Abramson S B. Nitric oxide:a novel mediator of inflammation [J]. Proc Soc Exp Biol Med. 1995,210(2):93-101.
[2]吴仪洛.本草从新[M].上海：上海科技出版社,1958.103.
[3]陶弘景,尚志钧辑校.本草经集注[M].芜湖：皖南医学院科研科印,1985：49.
[4]贾俊斌,田海生.误食生半夏中毒11例报道[J].中国乡村医生杂志,1999,15(3)：44.
[5]中医研究院中药研究所药理室、生药室炮制组.半夏炮制的毒性研究[J].新医药学杂志,1979,(7)：38-40
[6]罗国亮.半夏的毒性及临床应用[J].中草药,1999(2)：156.
[7]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421.[8]Seet B, Chan WK, Ang CL. Crystalline keratopathy from Dieffenbachia plant sap[J]. Br J Ophthalmol,1995,79: 98-99.
[9]Drach G, Maloney W. Toxicity of common houseplant Dieffebachia[J]. JAMA,1963,184:1047-1048.
[10]Lin TJ, Hung DZ, Hu WH, et al. Calcium oxalate is the main toxic component in clinical presentations of alocasis macrorrhiza (L) Schott and Endl poisonings[J]. Vet Hum Toxicol,1998,40(2):93-98.
[11]Hsueh KF, Lin PU, Lee SM, et al. Ocular injuries from plant sap of genera euphorbia and Dieffenbachia[J]. J ChinMed Assoc,2004,67:93.
[12]Van Ketel, Bruynzeel DP.Contact dermatitis to plants in Amsterdam[J]. Boll Dermatol Allergol Profess, 1987,2:132-144.
[13]吴皓,李伟,韩洪涛,等.半夏刺激性成分的研究[J].中国中药杂志,1999,24(12)：725-730.
[14]钟凌云,吴皓,张科卫,等.生半夏中草酸钙针晶的刺激性作用研究[J].中国中药杂志,2006,31(20)：1706-1710.
[15]葛秀云,吴皓.天南星科有毒中药毒针晶的组成成分分析[J].药物分析,2010,30(2)：190-193.
[16]吴皓,郁红礼,史闰均,等.凝集素：半夏及掌叶半夏毒针晶中的化学刺激性毒性成分[J].中药炮制技术、学术交流暨产业发展高峰论坛,2010,161-173.
[17]Ali BH, Blunden G, Tanira MO, et al. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe):A review of recent research[J]. Food and Chemical Toxicology, 2008,46:409-420.
[18]卢传坚,欧明,王宁生.姜的化学成分分析研究概述[J].中药新药与临床药理,2003,14(3)：215-217.
[19]李计萍,王跃生,马华,等.干姜与生姜主要化学成分的比较研究[J],中国中药杂志,2001,26(11)：748-751
[20]李海宁.生姜的抗动脉粥样硬化作用[J],国外医学.卫生学分册,2003,30(2)：98-101.
[21]张相年.姜精油的研究进展[J],广州化学,1992,(2)：65.
[22]李铁纯,回瑞华,侯冬岩,等.生姜挥发性成分的分析,分析科学学报,2003,19(5)：447-448.
[23]崔庆新,董岩.生姜挥发油化学成分的GC-MS分析研究,2006,19(2)：43-45.
[24]吴贾锋,张诚,张晓鸣,等.生姜风味物质的提取和成分分析[J].食品与机械,2006,23(3)：94-99.
[25]孙亚青,李景明,李丽梅.姜精油的Gc Ms分析研究[J].食品与发酵工业,2004,30(6)：95-99.
[26]D.W. Connell, R. McLachlan. Natural pungent compounds:Ⅳ. Examination of the gingerols, shogaols, paradols and related compounds by thin-layer and gas chromatography[J]. Journal of Chromatography A.1972, 67(1):29-35.
[27]王发松,胡海燕,黄世亮,等.姜油的分子蒸馏纯化与化学成分分析,中国医药工业杂志,2003,34(3)：125-127
[28]张维勒·姜辣素的测定方法[J].山东农业科学,1991(6)：11-14.
[29]黄雪松,王汉忠.姜辣素的测定方法[J]·中国调味品,1996(8)：30-31.
[30]杨春海,易杨慧,余爱农.溶出伏安法测定姜中姜辣素含量的研究,食品科学,2003,24(2)：110-112.
[31]张明昶,李健,蒙继昭.紫外分光光度法测定姜中姜辣素类化合物的含量[J].贵州医药,2003,27(3)：283-284.
[32]李凤华,张利民,孙淑华,等.生姜中姜辣素的提取及测定的研究[J].东北农业大学学报,2007,38(6)：746-749.
[33]王维皓,王智民,徐丽珍,等HPLC法测定生姜中有效成分6-姜辣素的含量[J].中国中药杂志,2002,27(5)：348-349.
[34]马雯雯,何前松,张永萍,等.高效液相色谱法测定生姜中6-姜酚的含量[J].微量元素与健康研究,2009, 26(6)：27-28.
[35]黄雪松,汪建民,王兆升.干姜、姜皮、泡姜中辣味成分的HPLC测定[J].中草药,1999,30(6)：423-424.
[36]陈燕,蔡同一,付力,等.用改进的高效液相色谱法(HPLC)测定姜中姜辣素[J].食品科学,2000,22(4)：60-63.
[37]张科卫,宋申,崔小兵,等.全国主要产区生姜中6-姜酚、6-姜醇含量的测定[J].中国药学杂志,2009,44(22)：1692-1694.
[38]Xian—Guo He. High performance Liquid chromatograph Electlo Spray Mass Spectrometric Analysis of Pungent Constituents of Ginger[J]. Journal of Chromatography A,1998,796(2):327.
[39]Kikuzaki H. Antioxidant effects of some ginger constituents[J]. J Food, Sci,1993,58(6):1407.
[40]Kikuzaki H, Kobayashi M, Nakatani N. Diarylheptanoids from rhizomes of zingiber ofeinale[J]. Phytochemistry,1991,30(11):3647-3651.
[41]Kikuzaki H, Nakatani N. Cyclic diaryl heptanoids from rhimmes of zingiber offeinale[J]. Phytochemistry, 1996,43(1):273-277.
[42]何文珊,李琳,李炎,等.生姜中一种新化合物的抗氧化活性[J].中国病理生理杂志,2002,17(5)：461.
[43]Jianping Ma, Xiaoling Jin, Li Yang, eta. Diarylheptanoids from the rhizomes of Zingiber officinale[J]. Phytochemistry,2004,65(8):1137-1143.
[44]Kiuchi F., Shibuya M., Sankawa U.. Inhibitors of prostaglandin biosynthesis from ginger[J]. Chem. Pharm. Bull,1982,30:754-757.
[45]Flynn D.L., Rafferty M.F., Boctor A.M.. Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds[J]. Prostaglandins Leukot Med,1986,24(2-3): 195-198.
[46]Charlier, C., Michaux, C. Dual inhibition of cyclooxygenase-2(COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs[J]. Eur. J. Med. Chem.,2003,38(7-8): 645-659.
[47]Grzanna R., Lindmark L., Frondoza C.G. Ginger-an herbal medicinal product with broad anti-inflammatory actions[J]. Journal of Medicinal Food,2005,8:125-132.
[48]Grzanna R., Phan P., Polotsky A., Lindmark L.,et al. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes[J]. J. Altern. Complement. Med.,2004,10: 1009-1013.
[49]Lantz R.C., Chen G.J., Sarihan M., et al. The effect of extracts from ginger rhizome on inflammatory mediator production[J]. Phytomedicine,2007,14:123-128.
[50]Mascolo N., Jain R., Jain S.C., et al. Ethnopharmacologic investigation of ginger (Zingibero□cinale)[J]. J. Ethnopharmacol.,1989,27,129-140.
[51]Kiuchi F., Iwakami S., Shibuya M., et al. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids[J]. Chem. Pharm. Bull.,1992,40:387-391.
[52]Young H.Y., Luo Y.L., Cheng H.Y., et al. Analgesic and anti-inflammatory activities of [6]-gingerol[J]. Journal of Ethnopharmacology,2005,96(1-2),207-210.
[53]Tripathi S., Maier K.G., Bruch D., et al. Effect of 6-Gingerol on Pro-Inflammatory Cytokine Production and Costimulatory Molecule Expression in Murine Peritoneal Macrophages[J]. Journal of Surgical Research, 2007,138(2):209-213.[54] Nurtjahja-Tjendraputra E., Ammit A.J., et al. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger[J]. Thromb. Res.,2003,111(4-5):259-265.[55] Dedov V.N., Tran V.H., Duke C.C., et al. Gingerols:a novel class of vanilloid receptor (VR1) agonists[J]. Br. J. Pharmacol.,2002,137(6):793-798.
[56]何文珊,魏孝义,李琳,等.生姜中一新的抗氧化二苯基环氧庚烷成分[J].植物学报,2001,43(7)：757-759.
[57]Masuda Y.,Kikuzaki H,Hisamot M,Nakatan N.Antioxidant properties of gingerol related compounds from ginger.BioFactors,2004,21(1-4):293-296.
[58]Katsunari Ippoushi, Atsuko Takeuchi, Hidekazu Ito,etal. Antioxidative effects of daikon sprout (Raphanus sativus L.) and ginger (Zingiber officinale Roscoe) in rats[J]. Food Chemistry.2007,102:237-242.
[59]I. Stoilova, A. Krastanov, A. Stoyanova, etal. Antioxidant activity of a ginger extract (Zingiber officinale)[J]. Food Chemistry,2007,102(3):764-770.
[60]杨雷香,周长新,黄可新,等.生姜中二苯庚烷类化合物的抗氧化[J].中国中药杂志,2009,34(3)：319-323.
[61]张霖,吴庆琛,张诚.生姜醇提取物对人肺腺癌细胞(A549)增殖和凋亡的影响[J].中国药房,2010,21(39)：3656-3658.
[62]Park K.K., Chun K.S., Lee J.M.,etal.. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett.1998,129:139-144.
[63]Liu H., Zhu Y.. Effect of alcohol extract of Zingiber officinale Rosc on immunologic function of mice with Tumor[J]. Wei Sheng Yan Jiu,2002,31(3):208-209.
[64]熊平源,马丙娜,郭明雄.生姜对小鼠免疫功能影响的实验研究[J],数理医药学杂志,2006,19(3)：243-244.
[65]李景舜,赵淑华,王春华,等.生姜提取物对X射线损伤免疫功能拮抗作用[J].中国公共卫生,2006,(2)：171-172.
[66]Mahady G B,Pendland S L.Ginger and the gingerols inhibit the growth of CagA+strains of Helicobater pylori. Anticancer Res.2003,23(5A):3699-3702.
[67]Thongson C, Davidson P M. Antimicrobial effect of Thai spices against listeria monocytogenes and Salmonella typhimurium DT104. J Food Prot,2005,68(10):2054-2058.
[68]刘瑜,张卫明,单承莺,等.生姜挥发油抑菌活性研究[J].食品工业科技,2008,(3)：88-90.
[69]姜正林,沈洪妹,杨凯.生姜与抗胆碱药的抗大鼠模拟运动病作用的比较观察[J].中华航海医学杂志, 1999,6(1)：20-22
[70]Willetts KE, Ekangaki A, Eden J A. Effect of a ginger extract on pregnancy-induced nausea:A randomised controlled trial[J]. Australian and New Zealand Journal of Obstetrics and Gynaecology.2003, 43(2):139-144
[71]Stripramote M, Lekhyananda N. A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy [J]. J Med Assoc Thai,2003,86(9):846-853.
[72]Sharma S S,Gupta Y K. Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale)[J]. Journal of ethnopharmacology,1998,62(1):49-55.
[73]赵德雪,杨志宏,李明,等.生姜对呕吐模型水貂止呕作用的研究[J],中国药事,2006,20(10)：601-104.
[74]卢传坚,欧明,王宁生.姜对心脑血管系统的药理作用[J].中药新药与临床药理.2003,14(5)：356-360.
[75]张明发,苏晓玲,沈雅琴.干姜现代药理研究概述[J].中国中医药科技.1996,3(2)：46.
[76]张竹心,刘连生.生姜油的抗过敏作用[J].中成药,1992,14(11)：30-31.
[77]Fuhrman B, Rosenbat M, Hayek T, et al. Ginger extract consumption reduced plasma cholesterol, inhibits LDL oxidation and attenuates development of atherosclerosis in atherosclerotic, apolipoprotein E3/deficient mice. J Nutr,2000,130(5):1124-1131.
[78]陈燕,田泽,葛毅强,等.姜油树脂调节血脂和抗血小板聚集作用的研究.营养学报,2001,23(4)：338-341.
[79]龚庆宣.刘涓子鬼遗方[M].北京：人民卫生出版社影印,1956.15.
[80]张在其.急性生半夏中毒14例临床分析[J].中国乡村医生杂志,2000,(6)：38.
[81]邵月如,夏俐俐.生半夏中毒及其解救[J].时珍国医国药,2000,11(8)：754.[82]Aniijima, Mkubo, Khashimoto, et al. Effect of oral administration of Pinellia ternata Zingiber rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve in the rat [J]. Neuroscience Letters,1998,258(1):5-8.
[83]吴皓,蔡宝昌,史小良,等.半夏姜制对动物刺激性及毒性的影响[J].中国中药杂志,1993,18(7)：408-410
[84]王金华,薛宝云.生姜与干姜药理活性的比较研究[J].中国药学杂志,2000,35(3)：163-165.
[85]吴皓,舒武琴,邱鲁婴,等.生姜解半夏毒的实验研究[J].中药材,1998,21(3)：137-140.
[86]吴皓,陆跃鸣,孙黎清,等.姜汁用量对姜浸半夏炮制品的影响[J].中药材,1998,21(6)：291-294
[87]魏伟,李晓辉,张洪泉,等.抗炎免疫药理学[M].2005,1：10-11.[88]吴皓,钟凌云,李伟,等.半夏炮制解毒机制的研究Ⅰ[J].中国中药杂志,2007,32(14)：1402-1405
[1]洪美玲主编.病理学[M].人民卫生出版社,1999：50.
[2]杨光华主编.病理学[M].第五版,人民卫生出版社.2001：57.
[3]王晓良.应用分子药理学[M].北京：中国协和医科大学出版社,2005：297-306.
[4]吴雪,秦明放.重症腹膜炎的致炎细胞因子研究进展[J].中国中西医结合外科杂志,2000,2(1)：61-63.
[5]Alam R. Chemokines in allergic inflammation[J]. J Allergy Clin Immumal.1997,99:273-277.
[6]杨卫红等.黏附分子与炎症.国外医学免疫分册[J].1999,22(1)：14-16.
[7]苏静怡.细胞粘附的生理与病理生理生理科学进展[J].1996,27(4)：374-382.
[8]Bredt D S, Snyder S H. Nitric Oxide as a neuronal messenger[J]. Trends PharmacolSci.1991,12(4): 125-128.
[9]李玉林.《分子病理学》[M].第一版,人民卫生出版社,2002：210-239.
[10]郭双平,翟宇强.核转录因子NF-κB的研究进展[J].中华病理学杂志.2000,29(5)：379-380
[11]杨刚.内分泌生理与病理生理学[M].第二版,天津科学技术出版社,1996,60-64
[12]张宏,彭成.附子抗免疫佐剂性关节炎的蛋白质组学研究[J].中华实用中西医杂志.2005,18(22)：1567-1569
[13]谢世荣,黄彩云,黄胜英.山豆根碱抗炎作用的研究[J].中草药.2003,34(4)：355-357
[14]鄢顺琴,凤良元,丁荣光.金钱白花蛇抗炎作用的实验研究[J].中药材,1994,17(12)：29-30.
[15]沈映君.中药“辛”味、挥发油、表证与炎症的关系[J].四川生理科学杂志,2004,26(4)：163
[16]赵璐,曾南.环氧化酶-2与中药抗炎作用的关系[J].中华中医药学刊,2008,26(1)：102-103.
[17]刘少平,董卫国,吴东方,等.阿魏酸钠对结肠炎大鼠结肠组织一氧化氮合酶和环氧合酶的影响[J].中国药理学通报,2003,19(5)：571-574.
[18]简燕婷,王继德,麦国丰,等.姜黄素对肠炎大鼠肠黏膜环氧合酶-2的调控[J].第四军医大学学报,2005,26(6)：521-524.
[19]黄秋菊,季晖,赖宜生,等.ZLJ-601抗炎作用及其机制研究[J].中国药科大学学报2008,39(4)：333-337
[20]刘芳,曲极冰,李红角,等.白藜芦醇抗炎作用机制的初步研究[J].中国药学杂志,2006,41(15)：1138-1141.
[21]王玮,白月,王俊平,等.黄芩茎叶总黄酮对大鼠气囊滑膜炎抗炎作用机制的研究[J].临床与用药,2009,26(4)：460.
[22]俊艳宁,朱秀坦,程桂芳.黄芩甙的抗炎机理[J].药理学报,2000,35(3)：161-164.
[23]覃仁安,梅璇,陈敏,等.鹅不食草挥发油抗炎作用及机制研究[J].2006,26(4)：369-371.
[24]崔晓燕,王素霞,候永利.金银花提取物的抗炎机制研究[J].中国药房,2007,18(24)：1861-1863.
[25]佟继铭,赵波,张玉玲.赤雹果水提物对佐剂性关节炎大鼠抗炎作用及机制研究[J].承德医学院学报,2010,27(4)：348-351.
[26]魏安祥,杨士友,阚红卫,等.柴黄复方颗粒抗炎镇痛作用及机制研究[J].中国实验方剂学杂志,2009,15(10)：82-84.
[27]肖振宇,张俊平,陆峰,等.商陆皂苷甲对细胞间粘附的影响[J].药学学报,2003,38(10)：728-730.
[28]郝钰,邱全瑛,吴珺,等.小檗碱对IL-1或TNF诱导的多形核白细胞与内皮细胞粘附的影响[J].中国病理生理杂志,2000,16(7)：585-58.
[29]唐旭东,姜建青,姜大春,等.三七总皂苷对心肌缺血在灌注中中性粒细胞核因子一KB活化及其粘附的影响.中国药理学通报,2002,18(5)：556-560.
[30]庞然,张淑玲,赵雷,等.蛇莓乙醇提取物的体外抗炎机制研究[J].华中科技大学学报(医学版),2009,38(4)：481-485.
[31]马涛,曹颖林,李欢,等.布洛芬川芎嗪酯的抗炎机制[J].沈阳药科大学学报,2005,22(4)：291-294.
[32]任俊,党月兰,李淑玉.红毛五加总甙抗炎机制研究[J].中药药理与临床,2002,18(6)：13-14.
[33]李淑慧,李晓辉,楚延.三七总皂苷抗炎作用机制的实验研究[J].中草药,2001,31(9)：676-678.
[34]李明春,雷林生,梁东升,等.灵芝多糖对小鼠腹腔巨噬细胞活性氧自由基的影响[J].中国药理学与毒理学杂志,2000,14(1)：65-68.
[35]宋媛嫒,李嫒,张洪泉.丁香苷抗炎镇痛作用及部分机制研究[J].中国野生植物资源,2010,29(4)：28-30.
[36]李文广,张小郁,吴勇杰,等.草血竭提取物抗炎作用和机制研究[J].中药药理与临床,2002,18(2)：18-20.
[37]张黎,陈志武,王瑜,等.银杏叶总黄酮抗炎作用及机制探讨[J].安徽医科大学学报,2001,36(5)：350-352
[38]姚余有,江礼生,陈敏珠.黄芪总黄酮对大鼠佐剂性关节炎的治疗作用及机制研究[J].中成药,2001,23(9)：661-663
[39]张骏,翁福海,李会强,等.大黄素对大鼠腹腔巨噬细胞产生TNF-α, IL-1, IL-6以及细胞内钙离子的影响[J].中草药,2001,32(8)：718-721.
[1]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421.
[2]中医研究院中药研究所药理室、生药室炮制组.半夏炮制的毒性研究[J].新医药杂志,1997,(7)：38-40.
[3]罗国亮.半夏的毒性及临床应用[J].中草药,1999,(2)：156.
[4]吴皓,李伟,韩洪涛,等.半夏刺激性成分的研究[J].中国中药杂志,1999,24(12)：725-730.
[5]钟凌云,吴皓,张科卫,等.生半夏中草酸钙针晶的刺激性作用研究[J].中国中药杂志,2006,31(20)：1706-1710.
[6]Seet B, Chan W.K., Ang C.L.. Crystalline keratopathy from Dieffenbachia plant sap[J]. Br J Ophthalmol, 1995,79:98-99.
[7]Lin T. J., Hung D. Z., Hu W. H., et al. Calcium oxalate is the main toxic component in clinical presentations of alocasis macrorrhiza (L) Schott and Endl poisonings[J]. Vet Hum Toxicol,1998,40(2):93-98.
[8]Hsueh K. F., Lin P. U., Lee S. M., et al. Ocular injuries from plant sap of genera euphorbia and Dieffenbachia[J]. J ChinMed Assoc,2004,67:93.
[9]陈奇.中药药理研究方法学[M].北京：人民卫生出版社,1996.306,364.
[10]黄秋菊,季晖,赖宜生.ZLJ2601抗炎作用及其机制研究[J].中国药科大学学报.2008,34(4)：333-337.
[11]魏伟,李晓辉,张洪泉,等.抗炎免疫药理学[M].2005,1,10-11.
[1]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421
[2]吴皓,李伟,韩洪涛,等.半夏刺激性成分的研究[J].中国中药杂志,1999,24(12)：725-730
[3]钟凌云,吴皓,张科卫,等.生半夏中草酸钙针晶的刺激性作用研究[J].中国中药杂志,2006,31(20)：1706-1710
[4]吴仪洛.本草丛新[M].上海科技出版社.1958：103
[5]陶弘景,尚志钧辑校.本草经集注[M].皖南医学院科研科印.1985：49
[6]张在其.急性生半夏中毒14例临床分析[J].中国乡村医生杂志,2000,(6)：38.
[7]邵月如,夏俐俐.生半夏中毒及其解救[J].时珍国医国药,2000,11(8)：754.
[8]Kiuchi F., Shibuya M., Sankawa U.. Inhibitors of prostaglandin biosynthesis from ginger[J]. Chem. Pharm. Bull,1982,30:754-757
[9]Grzanna R., Phan P., Polotsky A., Lindmark L.,et al. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes[J]. J. Altern. Complement. Med.,2004,10: 1009-1013
[10]Mascolo N., Jain R., Jain S.C., et al. Ethnopharmacologic investigation of ginger (Zingiber offcinale) [J]. J. Ethnopharmacol.,1989,27:129-140
[11]陈奇.中药药理研究方法学[M].人民卫生出版社.1996：306,364
[12]黄秋菊,季晖,赖宜生.ZLJ2601抗炎作用及其机制研究[J].中国药科大学学报.2008,34(4)：333-337
[13]Lantz R.C., Chen G.J., Sarihan M., et al. The effect of extracts from ginger rhizome on inflammatory mediator production[J]. Phytomedicine,2007,14:123-128.
[14]Mascolo N., Jain R., Jain S.C., et al. Ethnopharmacologic investigation of ginger (Zingibero□cinale)[J]. J. Ethnopharmacol.,1989,27,129-140.
[15]Young H.Y., Luo Y.L., Cheng H.Y., et al. Analgesic and anti-inflammatory activities of [6]-gingerol[J]. Journal of Ethnopharmacology,2005,96(1-2),207-210.
[1]卢传坚,欧明,王宁生.姜的化学成分分析研究概述[J].中药新药与临床药理,2003,14(3)：215-217.
[2]黄雪松,宴日安,吴建中.姜酚的生物活性述评[J].暨南大学学报(自然科学版),2005,26(3)：436-439.
[3]张雪红,李华昌.姜辣素的研究进展[J].矿冶,2003,12(4)：96-98.
[4]严赞开.姜酚的提取及抗氧化性试验[J].安徽农业科学.2006,34(4)：607,610.
[5]姜子涛,李荣.姜辣素化学及其研究进展[J].食品研究与开发,1998,19(1)：7-10.
[6]刘伟,刘成梅,李明,等.超声波萃取姜辣素工艺研究[J].中成药.2007,29(7)：1071-1073.
[7]唐仕荣,宋慧,刘全德,等.超声波-微波协同萃取姜辣素的工艺研究[J].食品与机械.2008,24(6)：76-79.
[8]田迪英,杨荣华.微波辐射对生姜抗氧化活性物质的浸提作用[J].国调味品,2006,(12)：17-21.
[1]刘瑜,张卫明,单承莺,等.生姜挥发油抑菌活性研究[J].食品工业科技,2008,(3),88-90
[2]王军,刘惠霞,张薇,等.生姜挥发油对脑缺血再灌注损伤的保护作用[J].2007,48(7)：644-646
[3]殷银霞,蔺兴遥.生姜挥发油的镇痛作用及其对胃溃疡大鼠血清中吲哚类神经递质的影响[J].卫生职业教育,2007,25(11)：142-143
[1]H.Y. Young, Y.L. Luo, H.Y. Cheng, etc. Analgesic and anti-inflammatory activities of [6]-gingerol[J]. Journal of Ethnopharmacology,2005,96:207-210
[2]黄雪松,宴日安,吴建中.姜酚的生物活性述评[J].暨南大学学报(自然科学版),2005,26(3)：436-439.
[3]S. Chrubasik, M.H. Pittler, B.D. Roufogalis. Zingiberis rhizoma:A comprehensive review on the ginger effect and efficacy profile[J]. Phytomedicine,2005,12:684-701
[4]张维勤.姜辣素的测定方法[J].山东农业科学,1999,(6)：11-14.
[5]黄雪松,王汉忠.姜辣素的测定方法[J].中国调味品,1996,(8)：30-32.
[6]郭晓斐,杜爱琴,杜爱玲.生姜中姜辣素含量的测定[J].山东化工,2007,36：34-37.
[7]张明昶,李健,蒙继昭.紫外分光光度法测定姜中姜辣素类化合物的含量[J].贵州医药2003,27(3)：283-284.
[8]李凤华,张利民,孙淑华,等.生姜中姜辣素的提取及测定的研究[J].东北农业大学学报,2007,38(6)：746-749.
[1]陈奇.中药药理研究方法学[M].人民卫生出版社.1996：306,364
[2]黄秋菊,季晖,赖宜生.ZLJ2601抗炎作用及其机制研究[J].中国药科大学学报.2008；34(4)：333-337
[1]梁鸿,赵玉英,李德宇,等.柴胡属植物化学成分及药理活性研究进展[J].国外医药·植物药分册,1999,14(5)：191.
[2]张宏,彭成.附子抗免疫佐剂性关节炎的蛋白质组学研究[J].中华实用中西医杂志.2005,18(22)：1567-1569
[3]陈万生,韩军,李力,等.知母总多糖的抗炎作用[J].第二军医大学学报,1999,20(10)：758.
[4]谢世荣,黄彩云,黄胜英.山豆根碱抗炎作用的研究[J].中草药.2003,34(4)：355-357.
[5]李仪奎.中药药理实验方法学[M].上海：上海科学技术出版社,1991：300.233-234.
[6]徐叔云,卞如濂,陈修.药理实验方法学,第三版[M].北京人民卫生出版社,2001：911-912,929-930.
[7]杨刚.内分泌生理与病理生理学[M].第二版,天津科学技术出版社,1996：60-64
[1]吴皓,季睿,邱鲁婴,等.半夏刺激性(动物实验)量化指标的研究[J].中成药,2000,22(6)：419-421.
[2]Grzanna R, Phan P, Polotsky A, Lindmark L,et al. Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes[J]. J. Altern. Complement. Med.,2004,10: 1009-1013.
[3]Kiuchi F, Iwakami S, Shibuya M, et al. Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids[J]. Chem. Pharm. Bull.,1992,40:387-391.
[4]Tripathi S, Maier KG, Bruch D, et al. Effect of 6-Gingerol on Pro-Inflammatory Cytokine Production and Costimulatory Molecule Expression in Murine Peritoneal Macrophages[J]. Journal of Surgical Research,2007, 138(2):209-213.
[5]杨世杰主编.药理学[M].人民卫生出版社,2001,421
[6]周武庆.一氧化氮在炎症和免疫调节中的作用[J].国外医学皮肤性病学分册.1999,25(4)：233-235.
[7]Moncada S, Palmer RM. Inhibition of the induction of nitric oxide synthase by glucocorticoids:yet another explanation for their anti-inflammatory effects?[J]. TrendsPharmacolSei.1991,12(4):130-131
[8]Snyder S H, Bredt D S. Nitric oxide as a neuronal messenger[J]. Trends Pharmacol Sci.1991,12(4): 125-128.
[9]Clancy R M, Abramson S B. Nitric oxide:a novel mediator of inflammation [J]. Proc Soc Exp Biol Med. 1995,210(2):93-101.