霉菌毒素之間的互作效應

來源： 赤峰和美嘉科技有限公司  點擊：26 發(fā)布時間：2017-3-22

近年來的養(yǎng)殖實踐發(fā)現(xiàn)，幾種霉菌毒素協(xié)同作用對動物健康和生產(chǎn)性能產(chǎn)生的副作用比一種霉菌毒素單獨作用的副作用更大。實際生產(chǎn)條件下引起動物生產(chǎn)性能下降和中毒癥的霉菌毒素的含量往往遠低于實驗控制條件下引起同樣毒性效應的單一霉菌毒素劑量。研究顯示，與飼喂純化的霉菌毒素相比，飼喂自然污染霉菌毒素的飼料產(chǎn)生的中毒癥狀更為嚴重。此外，霉菌毒素間的互作可以改變中毒的臨床癥狀，導致一系列診斷特征不同于單獨作用的癥狀之和。這使得田間診斷變得困難。

霉菌毒素互作效應可分為加性效應、亞加性效應、協(xié)同效應、增效效應和頡頏效應。加性效應（Additiveeffects）是指兩種霉菌毒素的組合作用等于二者單一作用的累積相加。協(xié)同效應（Synergistic effects）指兩種霉菌毒素的組合作用高于二者單一作用的累積相加。上述兩種互作效應在鐮孢菌屬（鐮刀菌屬）的毒素之間最常見，發(fā)生得最嚴重。亞加性效應（Less than additive effects）發(fā)生于兩種霉菌毒素的組合作用低于二者單一作用的累積相加。增效效應（Potentiative effects）是指一種霉菌毒素對某組織或器官不產(chǎn)生毒性作用，但攝入另一霉菌毒素后，前者使后者毒性增強。頡頏效應（Antagonistic effects）是指一種霉菌毒素干擾另一種霉菌毒素的毒性作用。這種情況很少見。

一、黃曲霉毒素和鐮刀菌屬霉菌毒素之間的互作效應

研究發(fā)現(xiàn)，當日糧中同時存在黃曲霉毒素和T-2毒素這兩種霉菌毒素時，相互作用表現(xiàn)為加性效應或亞加性效應。對肉仔雞同時飼喂黃曲霉毒素和蛇形毒素，從體增重、平均紅細胞體積、平均紅細胞血紅蛋白含量、血清甘油三酯、血清鈣等指標看，二者的毒性互作效應表現(xiàn)為協(xié)同效應。生長豬飼喂同時含黃曲霉毒素B₁和煙曲霉毒素B_l的日糧，無論日糧含有一種霉菌毒素還是同時含有二種霉菌毒素，都對其臨床表現(xiàn)、生物化學、血液學和免疫學指標產(chǎn)生不利的影響。

總的來說，動物對采食有多種霉菌毒素并存的日糧的反應要大于這些霉菌毒素單獨存在時的反應，毒性的反應是累加的，有時毒性反應比單獨的霉菌毒素累加后還大，表現(xiàn)為協(xié)同效應，尤其是對動物的肝臟損傷。

二、赭曲霉毒素和其他霉菌毒素之間的互作效應

在赭曲霉毒素A和T-2毒素對生長閹豬影響的研究中發(fā)現(xiàn)，它們對豬的生長性能、血清生化指標、血清學指標、免疫機能和器官組織重量相互作用是累加性的。生長豬采食同時含有赭曲霉毒素A、脫氧雪腐鐮刀菌烯醇和玉米赤霉烯酮的日糧90 天，結果發(fā)現(xiàn)，在豬組織中并沒有檢測到脫氧雪腐鐮刀菌烯醇和玉米赤霉烯酮，但日糧中同時含有脫氧雪腐鐮刀菌烯醇和玉米赤霉烯酮影響了豬體內赭曲霉毒素A的排泄。從顯微鏡的觀察結果可以看出，赭曲霉毒素A和青霉菌酸對青年豬的毒性作用，豬的腎臟受損不同于典型的丹麥豬腎臟病。這說明赭曲霉毒素A和青霉菌酸之間可能存在協(xié)同作用。

三、煙曲霉毒素B₁和其他鐮刀菌屬霉菌毒素之間的互作效應

煙曲霉毒素B₁和脫氧雪腐鐮刀菌烯醇對生長閹豬的生長性能、血清生化指標、免疫反應和組織病理學反應存在加性互作效應；而從另一些指標的分析結果看，則存在超出累加性的互作，表現(xiàn)為協(xié)同效應。

四、脫氧雪腐鐮刀菌烯醇和其他鐮刀菌屬霉菌毒素之間的互作效應

研究發(fā)現(xiàn)，日糧脫氧雪腐鐮刀菌烯醇和T-2毒素之間存在明顯的毒理學協(xié)同作用。將天然霉變的玉米，其中含有雪腐鐮刀菌烯醇11.5 mg/kg和玉米赤霉烯酮3mg/kg的日糧分別飼喂給生長豬和妊振母豬，結果發(fā)現(xiàn)，生長豬的采食量減少，平均日增重下降，飼料轉化效率降低。

表1和表2分別總結了飼料中一些常見霉菌毒素對豬禽的毒性互作效應。由于生理反應變量對生物學和經(jīng)濟學影響的統(tǒng)計結果具有不確定性，研究僅限于兩種霉菌毒素的互作效應對動物生產(chǎn)性能的影響。

以上結果并不代表動物實際生產(chǎn)中癥狀（實際生產(chǎn)中可能更嚴重），存在一些不足，如霉菌毒素劑量很高時它們之間的互作效應就難以發(fā)現(xiàn)，因為某種單一毒素產(chǎn)生的毒性反應可能已經(jīng)達最大。而且現(xiàn)有的研究多數(shù)沒有考慮毒性反應對免疫系統(tǒng)的影響。據(jù)報道，多種霉菌毒素誘導的免疫抑制可能使動物對影響生產(chǎn)性能的致病因子的易感性增加。另一個不足之處是，現(xiàn)有的研究僅評估兩種霉菌毒素的互作效應，但實際上受污染飼料含有的霉菌毒素可能不止兩種。此外這些研究是在實驗室條件下進行的，動物一般接觸不到環(huán)境應激因子（如熱、NH₃、疾病等）

表1 霉菌毒素對豬的毒性互作效應

霉菌毒素	動物種類	互作類型	資料來源
黃曲霉毒素和T-2毒素	生長豬	加性效應	Harvey等，1990；1995
黃曲霉毒素和嘔吐毒素	生長豬	亞加性效應	Harvey 等，1989
黃曲霉毒素和蛇形毒素	生長豬	加性效應	Harvey 等，1991
黃曲霉毒素和煙曲霉毒素B1	生長豬	協(xié)同效應	Harvey 等， 1995
赭曲霉毒素A和T-2毒素	生長豬	亞加性效應	Harvey 等， 1994
煙曲霉毒素B1和嘔吐毒素	生長豬	協(xié)同效應	Harvey 等， 1996
煙曲霉毒素B1和串珠鐮刀菌毒素	生長豬	加性效應	Harvey 等， 1989；1997
黃曲霉毒素和赭曲霉毒素A	生長豬	亞加性效應	Tapia 和 Seawright，1985
赭曲霉毒素A和T-2毒素	生長豬(閹豬)	加性效應	Harvey等，1994；Lusky等，1998
赭曲霉毒素A和青霉酸	小豬	協(xié)同效應	Stoev等，2001
嘔吐毒素和T-2毒素	生長豬	沒有互作證據(jù)	Friend等，1992; Rotter等，1992

表2 霉菌毒素對禽的毒性互作效應

霉菌毒素	動物種類	互作效應	資料來源
黃曲霉毒素和赭曲霉毒素A	雞	協(xié)同效應a 亞加性效應b	Huff  等a，1981；Huff等a，1984； Huff  等 b， 1992
黃曲霉毒素和 T-2毒素	雞	協(xié)同效應	Huff  等，1988；Kubena 等，1990
黃曲霉毒素和蛇形毒素	雞	協(xié)同效應	Kubena  等，1993
黃曲霉毒素和嘔吐毒素	雞	加性效應	Huff  等，  1986
黃曲霉毒素和煙曲霉毒素B1	雛火雞	加性效應 僅黃曲霉毒素受影響	Kubena  等，1995；Weibking等，1994
黃曲霉毒素和環(huán)匹阿尼酸	雞	亞加性效應	Smith  等，  1992
黃曲霉毒素和酒曲酸	雞	加性效應	Giroir  等，  1991
黃曲霉毒素和串珠鐮刀菌毒素	雞	亞加性效應	Kubena  等，  1997
赭曲霉毒素A和T-2毒素	雞	加性效應	Kubena  等，  1989
煙曲霉毒素B1和嘔吐毒素	雞	僅黃曲霉毒素受影響	Kubena  等，  1997
嘔吐毒素和串珠鐮刀菌毒素	雞	亞加性效應	Harvey  等，  1997
嘔吐毒素和串珠鐮刀菌毒素	雛火雞	僅串珠鐮刀菌毒素受影響	Morris  等，  1999
嘔吐毒素和T-2毒素	雞	加性效應	Kubena  等，  1989
煙曲霉毒素B1 和串珠鐮刀菌毒素	蛋雞	僅黃曲霉毒素受影響	Kubena  等，  1999
煙曲霉毒素B1 和串珠鐮刀菌毒素	雛火雞	僅串珠鐮刀菌毒素受影響	Li  等，  2000
煙曲霉毒素B1和T-2毒素	雛火雞	加性效應	Kubena  等，  1995
煙曲霉毒素B1和T-2毒素	雞	亞加性效應	Kubena  等，  1997
煙曲霉毒素B1和蛇形毒素	雛火雞	加性效應	Kubena  等，  1997
煙曲霉毒素B1和赭曲霉毒素A	雛火雞	加性效應	Kubena  等，  1997
赭曲霉毒素A和青霉酸	雞	僅赭曲霉毒素A受影響	Kubena  等，  1984
赭曲霉毒素A和橘霉毒素	雞	頡頏效應	Manning  等，  1985
赭曲霉毒素A和嘔吐毒素	雞	加性效應	Kubena  等，  1988
赭曲霉毒素A和蛇形毒素	雞	亞加性效應	Kubena  等，  1994
環(huán)匹阿尼酸和T-2毒素	雞	亞加性效應	Kubena  等，  1994

飼喂仔豬同時含有脫氧雪腐鐮刀菌烯醇、15-乙酰去氧雪腐鐮菌醇、玉米赤霉烯酮和鐮刀菌酸的天然霉變玉米和小麥配制的日糧，結果發(fā)現(xiàn)，仔豬的增重和采食量明顯地下降；同時，仔豬大腦的神經(jīng)化學指標發(fā)生變化�？赡苡捎谶@些霉菌毒素在日糧中共同存在對大腦神經(jīng)化學所產(chǎn)生了不同的影響所致。

霉菌毒素之間的相互作用，很大程度上會加重動物霉菌毒素的中毒癥狀，這導致了實際飼料中的霉菌毒素含量不高，但動物卻出現(xiàn)中毒癥狀。因此，考慮飼料受霉菌毒素污染狀況，不能一味的參照國家標準，應綜合考慮各種毒素之間的相互作用，建立適合實際生產(chǎn)中的標準，防治動物霉菌毒素中毒。

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.