霉菌毒素之间的互作效应

来源： 赤峰和美嘉科技有限公司  点击：26 发布时间：2017-3-22

近年来的养殖实践发现，几种霉菌毒素协同作用对动物健康和生产性能产生的副作用比一种霉菌毒素单独作用的副作用更大。实际生产条件下引起动物生产性能下降和中毒症的霉菌毒素的含量往往远低于实验控制条件下引起同样毒性效应的单一霉菌毒素剂量。研究显示，与饲喂纯化的霉菌毒素相比，饲喂自然污染霉菌毒素的饲料产生的中毒症状更为严重。此外，霉菌毒素间的互作可以改变中毒的临床症状，导致一系列诊断特征不同于单独作用的症状之和。这使得田间诊断变得困难。

霉菌毒素互作效应可分为加性效应、亚加性效应、协同效应、增效效应和颉颃效应。加性效应（Additiveeffects）是指两种霉菌毒素的组合作用等于二者单一作用的累积相加。协同效应（Synergistic effects）指两种霉菌毒素的组合作用高于二者单一作用的累积相加。上述两种互作效应在镰孢菌属（镰刀菌属）的毒素之间最常见，发生得最严重。亚加性效应（Less than additive effects）发生于两种霉菌毒素的组合作用低于二者单一作用的累积相加。增效效应（Potentiative effects）是指一种霉菌毒素对某组织或器官不产生毒性作用，但摄入另一霉菌毒素后，前者使后者毒性增强。颉颃效应（Antagonistic effects）是指一种霉菌毒素干扰另一种霉菌毒素的毒性作用。这种情况很少见。

一、黄曲霉毒素和镰刀菌属霉菌毒素之间的互作效应

研究发现，当日粮中同时存在黄曲霉毒素和T-2毒素这两种霉菌毒素时，相互作用表现为加性效应或亚加性效应。对肉仔鸡同时饲喂黄曲霉毒素和蛇形毒素，从体增重、平均红细胞体积、平均红细胞血红蛋白含量、血清甘油三酯、血清钙等指标看，二者的毒性互作效应表现为协同效应。生长猪饲喂同时含黄曲霉毒素B₁和烟曲霉毒素B_l的日粮，无论日粮含有一种霉菌毒素还是同时含有二种霉菌毒素，都对其临床表现、生物化学、血液学和免疫学指标产生不利的影响。

总的来说，动物对采食有多种霉菌毒素并存的日粮的反应要大于这些霉菌毒素单独存在时的反应，毒性的反应是累加的，有时毒性反应比单独的霉菌毒素累加后还大，表现为协同效应，尤其是对动物的肝脏损伤。

二、赭曲霉毒素和其他霉菌毒素之间的互作效应

在赭曲霉毒素A和T-2毒素对生长阉猪影响的研究中发现，它们对猪的生长性能、血清生化指标、血清学指标、免疫机能和器官组织重量相互作用是累加性的。生长猪采食同时含有赭曲霉毒素A、脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮的日粮90 天，结果发现，在猪组织中并没有检测到脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮，但日粮中同时含有脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮影响了猪体内赭曲霉毒素A的排泄。从显微镜的观察结果可以看出，赭曲霉毒素A和青霉菌酸对青年猪的毒性作用，猪的肾脏受损不同于典型的丹麦猪肾脏病。这说明赭曲霉毒素A和青霉菌酸之间可能存在协同作用。

三、烟曲霉毒素B₁和其他镰刀菌属霉菌毒素之间的互作效应

烟曲霉毒素B₁和脱氧雪腐镰刀菌烯醇对生长阉猪的生长性能、血清生化指标、免疫反应和组织病理学反应存在加性互作效应；而从另一些指标的分析结果看，则存在超出累加性的互作，表现为协同效应。

四、脱氧雪腐镰刀菌烯醇和其他镰刀菌属霉菌毒素之间的互作效应

研究发现，日粮脱氧雪腐镰刀菌烯醇和T-2毒素之间存在明显的毒理学协同作用。将天然霉变的玉米，其中含有雪腐镰刀菌烯醇11.5 mg/kg和玉米赤霉烯酮3mg/kg的日粮分别饲喂给生长猪和妊振母猪，结果发现，生长猪的采食量减少，平均日增重下降，饲料转化效率降低。

表1和表2分别总结了饲料中一些常见霉菌毒素对猪禽的毒性互作效应。由于生理反应变量对生物学和经济学影响的统计结果具有不确定性，研究仅限于两种霉菌毒素的互作效应对动物生产性能的影响。

以上结果并不代表动物实际生产中症状（实际生产中可能更严重），存在一些不足，如霉菌毒素剂量很高时它们之间的互作效应就难以发现，因为某种单一毒素产生的毒性反应可能已经达最大。而且现有的研究多数没有考虑毒性反应对免疫系统的影响。据报道，多种霉菌毒素诱导的免疫抑制可能使动物对影响生产性能的致病因子的易感性增加。另一个不足之处是，现有的研究仅评估两种霉菌毒素的互作效应，但实际上受污染饲料含有的霉菌毒素可能不止两种。此外这些研究是在实验室条件下进行的，动物一般接触不到环境应激因子（如热、NH₃、疾病等）

表1 霉菌毒素对猪的毒性互作效应

霉菌毒素	动物种类	互作类型	资料来源
黄曲霉毒素和T-2毒素	生长猪	加性效应	Harvey等，1990；1995
黄曲霉毒素和呕吐毒素	生长猪	亚加性效应	Harvey 等，1989
黄曲霉毒素和蛇形毒素	生长猪	加性效应	Harvey 等，1991
黄曲霉毒素和烟曲霉毒素B1	生长猪	协同效应	Harvey 等， 1995
赭曲霉毒素A和T-2毒素	生长猪	亚加性效应	Harvey 等， 1994
烟曲霉毒素B1和呕吐毒素	生长猪	协同效应	Harvey 等， 1996
烟曲霉毒素B1和串珠镰刀菌毒素	生长猪	加性效应	Harvey 等， 1989；1997
黄曲霉毒素和赭曲霉毒素A	生长猪	亚加性效应	Tapia 和 Seawright，1985
赭曲霉毒素A和T-2毒素	生长猪(阉猪)	加性效应	Harvey等，1994；Lusky等，1998
赭曲霉毒素A和青霉酸	小猪	协同效应	Stoev等，2001
呕吐毒素和T-2毒素	生长猪	没有互作证据	Friend等，1992; Rotter等，1992

表2 霉菌毒素对禽的毒性互作效应

霉菌毒素	动物种类	互作效应	资料来源
黄曲霉毒素和赭曲霉毒素A	鸡	协同效应a 亚加性效应b	Huff  等a，1981；Huff等a，1984； Huff  等 b， 1992
黄曲霉毒素和 T-2毒素	鸡	协同效应	Huff  等，1988；Kubena 等，1990
黄曲霉毒素和蛇形毒素	鸡	协同效应	Kubena  等，1993
黄曲霉毒素和呕吐毒素	鸡	加性效应	Huff  等，  1986
黄曲霉毒素和烟曲霉毒素B1	雏火鸡	加性效应 仅黄曲霉毒素受影响	Kubena  等，1995；Weibking等，1994
黄曲霉毒素和环匹阿尼酸	鸡	亚加性效应	Smith  等，  1992
黄曲霉毒素和酒曲酸	鸡	加性效应	Giroir  等，  1991
黄曲霉毒素和串珠镰刀菌毒素	鸡	亚加性效应	Kubena  等，  1997
赭曲霉毒素A和T-2毒素	鸡	加性效应	Kubena  等，  1989
烟曲霉毒素B1和呕吐毒素	鸡	仅黄曲霉毒素受影响	Kubena  等，  1997
呕吐毒素和串珠镰刀菌毒素	鸡	亚加性效应	Harvey  等，  1997
呕吐毒素和串珠镰刀菌毒素	雏火鸡	仅串珠镰刀菌毒素受影响	Morris  等，  1999
呕吐毒素和T-2毒素	鸡	加性效应	Kubena  等，  1989
烟曲霉毒素B1 和串珠镰刀菌毒素	蛋鸡	仅黄曲霉毒素受影响	Kubena  等，  1999
烟曲霉毒素B1 和串珠镰刀菌毒素	雏火鸡	仅串珠镰刀菌毒素受影响	Li  等，  2000
烟曲霉毒素B1和T-2毒素	雏火鸡	加性效应	Kubena  等，  1995
烟曲霉毒素B1和T-2毒素	鸡	亚加性效应	Kubena  等，  1997
烟曲霉毒素B1和蛇形毒素	雏火鸡	加性效应	Kubena  等，  1997
烟曲霉毒素B1和赭曲霉毒素A	雏火鸡	加性效应	Kubena  等，  1997
赭曲霉毒素A和青霉酸	鸡	仅赭曲霉毒素A受影响	Kubena  等，  1984
赭曲霉毒素A和橘霉毒素	鸡	颉颃效应	Manning  等，  1985
赭曲霉毒素A和呕吐毒素	鸡	加性效应	Kubena  等，  1988
赭曲霉毒素A和蛇形毒素	鸡	亚加性效应	Kubena  等，  1994
环匹阿尼酸和T-2毒素	鸡	亚加性效应	Kubena  等，  1994

饲喂仔猪同时含有脱氧雪腐镰刀菌烯醇、15-乙酰去氧雪腐镰菌醇、玉米赤霉烯酮和镰刀菌酸的天然霉变玉米和小麦配制的日粮，结果发现，仔猪的增重和采食量明显地下降；同时，仔猪大脑的神经化学指标发生变化。可能由于这些霉菌毒素在日粮中共同存在对大脑神经化学所产生了不同的影响所致。

霉菌毒素之间的相互作用，很大程度上会加重动物霉菌毒素的中毒症状，这导致了实际饲料中的霉菌毒素含量不高，但动物却出现中毒症状。因此，考虑饲料受霉菌毒素污染状况，不能一味的参照国家标准，应综合考虑各种毒素之间的相互作用，建立适合实际生产中的标准，防治动物霉菌毒素中毒。

The English version

Farming practices found in recent years, several kinds of mycotoxin synergy effects for animal health and production performance is better than the side effects of a mycotoxin role separately. The actual production conditions cause animal production performance degradation and poisoning the content of mycotoxin often far lower than the experimental control conditions cause the same toxic effect of single dose mycotoxin. Research shows that, compared with feeding and purification of mycotoxin feeding mycotoxin feed produced by natural pollution poisoning symptoms are more severe than others. In addition, the interactions between the mycotoxin could change clinical symptoms of poisoning, cause the symptom of a series of diagnostic characteristics different from the separate function combined. This makes it difficult to diagnosis field.

Mycotoxin interaction effect can be divided into additive effect, the additive effect, synergies, synergistic effect and the effect of the rivalry. Additive effect (Additiveeffects) refers to the two kinds of combination of mycotoxin effect is equal to the accumulation of both single function together. Synergistic effect (Synergistic effects) refers to two kinds of mycotoxin combination is higher than the accumulation of both single function together. Interaction effect is both in the genus fusarium oxysporum toxin between sickle (species) is the most popular, the worst happened. The additive effect (Less than additive effects) occurred from a combination of two kinds of mycotoxin below the accumulation of both single function together. Synergistic effect (Potentiative effects) is a mycotoxin on a tissue or organ does not produce toxic effect, but after another mycotoxin intake, increase toxicity of the former to the latter. Rivalry effect (Antagonistic effects) is a mycotoxin interfering with another mycotoxin toxic effects. It is a rare situation.

A, aflatoxin and sickle bacterial interaction effect between the mycotoxin

 the study found that day at the same time exist aflatoxin in food and the two T - 2 toxin mycotoxin, interaction of additive effect or the additive effect. The broiler chickens fed aflatoxin and snake toxins at the same time, from body weight, average red blood cell volume, the average content of red blood cells, hemoglobin, serum triglycerides, indices such as serum calcium, the toxicity of both interaction effect of synergistic effect. Growing swine feeding at the same time containing aflatoxin B1 and smoke aspergillus toxin Bl of the diet, regardless of the diet contains a mycotoxin or contains two kinds of mycotoxin at the same time, all the clinical manifestation, biochemical, hematology and immunological indexes produced adverse effect.

In general, the coexistence of animal feed on a variety of mycotoxin diet response than the response to these mycotoxins individually, toxicity reaction is cumulative, sometimes toxic effects than single after the mold toxin accumulation, characterized by synergistic effect, especially liver injury of animals.

Second, ochre and aspergillus toxin and other interaction effect between the mycotoxin

In ochratoxin A and T 2 toxin discovered in the research on the effects of growth to castrate pigs, they to the pig growth performance, serum biochemical indexes, serological indexes, immune function and tissues is A cumulative weight interaction. Growing swine feeding at the same time contains ochratoxin A sickle, deoxidization snow fungus ene alcohol and corn gibberellic ketene diet for 90 days, the results found that DNA was not detected in pig tissue snow sickle bacteria and corn gibberellic ketene, but in the diet also contains the snow sickle bacteria ene alcohol and corn gibberellic ketene affected pigs ochratoxin A drain. Can be seen from the microscope observation, ochratoxin A and penicillium acid toxic effect of young pigs, pig kidney damage is different from the typical Danish pig kidney disease. This shows that ochratoxin A possible synergies between acid and penicillium.

Three, smoke aspergillus toxin B1 and other interactions between sickle bacteria is a mycotoxin effects

Smoke aspergillus toxin B1 and deoxidization snow enol sickle bacteria to grow yan pig growth performance, serum biochemical indicator, immune response and histopathologic response additive interactions effect; The analysis results of some indicators from another country, there are beyond the interactions of a cumulative, show the synergy effect.

Four, deoxidization snow sickle bacteria ene alcohol and other sickle bacteria genera interaction effect between the mycotoxin

The study found that the diet deoxidization snow sickle ene alcohol and T - 2 toxins obviously toxicology synergy between. Will naturally mouldy corn, among them with snow sickle bacteria enol 11.5 mg/kg and corn gibberellic ketene 3 mg/kg of diet feeding for growing pigs and pregnancy sow respectively, the results found that growth of pig feed intake decreases, the average daily gain, feed conversion efficiency reduced.

Table 1 and table 2 respectively, summarizes some common mycotoxins in feed to pigs poultry interaction effect of toxicity. Due to physiological response variables impact on the biological and economic uncertainty, the results of the research is limited to two kinds of mycotoxin interaction effect on the properties of animal production.

These results do not represent the animal symptoms in the process of production (may be more serious in the process of production), some deficiencies, such as mycotoxins very high doses of the interaction effect between them can be difficult to find, because a single toxins produced by toxic reaction might have been the largest. But most existing research does not consider the effects of toxic effects on the immune system. According to the report, a variety of mycotoxin induced immunosuppression may make animal pathogenic factor of affecting production performance increase susceptibility. Another deficiency is that the study of existing evaluation of two kinds of the interaction effect of mycotoxin, but in fact the contaminated feed containing mycotoxins may be more than two. In addition the study was conducted under laboratory conditions, animal generally are not exposed to environmental stress factors (such as thermal, NH3, disease, etc.)

Table 1 mycotoxin toxic interaction effect of pigs

Mycotoxin animal species interactions type source

Aflatoxin and T - 2 toxin additive effect growing swine Harvey, etc., 1990; 1995

Aflatoxin and vomiting toxins pig growth and the additive effect Harvey, etc., 1989

Aflatoxin and snake poison additive effect growing swine Harvey, etc., 1991

Aspergillus toxin aflatoxin and smoke B1 growing swine synergies Harvey, etc., 1995

Ochratoxin A growing swine and T - 2 toxin and additive effect Harvey, etc., 1994

Smoke aspergillus toxin B1 and vomiting toxins growing swine synergies Harvey, etc., 1996

Smoke aspergillus toxin B1 and beaded sickle fungus toxin additive effect growing swine Harvey, etc., 1989; 1997

Aflatoxin and ochratoxin A pig growth and the additive effect Tapia and Seawright, 1985

Ochratoxin A growing pigs and T - 2 toxin (yan pigs) additive effect Harvey, etc., 1994; Lusky etc., 1998

Ochratoxin A pig synergies and penicillium acid Stoev, etc., 2001

Vomiting toxins growth and T - 2 pig Friend no interactions evidence, etc., 1992; Rotter, etc., 1992

Table 2 mycotoxin on avian interaction effect of toxicity

Mycotoxin animal species interactions effect data sources

Yellow aspergillus toxin and ochratoxin A synergistic effect of A chicken

The additive effect Huff, etc. A, b, 1981; Huff, etc. A, 1984;

Huff, etc. B, 1992

Aflatoxin and T - 2 toxin chicken synergies Huff, etc., 1988; Kubena, etc., 1990

Aflatoxin and snake poison chicken synergies Kubena, etc., 1993

Aflatoxin and vomiting toxins chicken additive effect Huff, etc., 1986

Aspergillus toxin aflatoxin and smoke B1 baby turkeys additive effect

Only yellow aspergillus toxin affected Kubena, etc., 1995; Weibking, etc., 1994

Aflatoxin and chicken and horse ANI acid additive effect Smith, etc., 1992

Aflatoxin and could sour chicken Giroir additive effect, etc., 1991

Aflatoxin and beaded sickle fungus toxin chicken and additive effect Kubena, etc., 1997

Ochratoxin A chicken and T - 2 toxin additive effect Kubena, etc., 1989

Smoke aspergillus toxin and vomiting toxins chicken only aflatoxin B1 affected Kubena, etc., 1997

Vomiting toxins and beaded sickle fungus toxin chicken and additive effect Harvey, etc., 1997

Vomiting toxins and beaded sickle bacteria toxin baby turkeys beaded sickle only bacteria toxins affected Morris, etc., 1999

Vomiting toxins chicken additive effect and T - 2 Kubena, etc., 1989

Smoke aspergillus toxin B1 and beaded sickle fungus toxin aflatoxin only affected layers are Kubena, etc., 1999

Smoke aspergillus toxin B1 and beaded sickle bacteria toxin baby turkeys beaded sickle only bacteria toxins affected Li, etc., 2000

Smoke aspergillus toxin B1 and T - 2 toxin baby turkeys additive effect Kubena, etc., 1995

Smoke aspergillus toxin B1 and T - 2 toxin chicken and additive effect Kubena, etc., 1997

Smoke aspergillus toxin B1 and snake poison baby turkeys additive effect Kubena, etc., 1997

Smoke aspergillus toxin B1 and ochratoxin A baby turkeys additive effect Kubena, etc., 1997

Ochratoxin A chicken and penicillium acid only ochratoxin A affected Kubena, etc., 1984

Ochratoxin A chicken and orange mold toxin Manning rivalry effect, etc., 1985

Ochratoxin A chicken and vomiting toxins additive effect Kubena, etc., 1988

Ochratoxin A chicken and snake toxins and additive effect Kubena, etc., 1994

Ring horse ANI acid and T - 2 toxin chicken and additive effect Kubena, etc., 1994

Feeding piglets at the same time contains the snow sickle bacteria enol, 15 - acetyl deoxidation snow fungus alcohol unit, corn gibberellic acid ketene and sickle bacterium natural mildew wheat and corn diet, found that weight gain and feed intake of the piglets obviously decreased; At the same time, the piglets brain neurochemical index change. May be due to the mycotoxin exist together in the diet neural chemistry, produces different effects on the brain.

Interaction between mycotoxin, will greatly increase the animal mycotoxin poisoning symptoms, this led to the actual content of the mycotoxins in feed is not high, but the animal poisoning symptoms. Therefore, considering the condition feed contaminated with mycotoxins, not blindly reference to national standards, should be considered the interaction between various toxin, the standard is suitable for the actual production, the mold toxin poisoning prevention and treatment of animals.