無脊椎動物家蠶為材料的醫(yī)學實驗動物替代研究
發(fā)布時間：2018-07-16 08:07
【摘要】：實驗動物替代方法,已廣泛應用于生命科學研究領域。家蠶是鱗翅目模式昆蟲,有著數(shù)千年畜牧化養(yǎng)殖歷史,且已積累了系統(tǒng)深入的生理學、病理學和毒理學資料。家蠶遺傳突變資源的創(chuàng)新及其在基礎生命體系、物質代謝、能量代謝和遺傳方式上與哺乳類有眾多相似性的發(fā)現(xiàn),使家蠶作為中國特色的模式昆蟲正逐漸向實驗動物模式化發(fā)展。然而,如何通過系統(tǒng)地控制實驗用家蠶的遺傳因素和生長環(huán)境,實現(xiàn)家蠶“實驗動物化”,如何根據(jù)家蠶的生物學特性,優(yōu)選出替代方法研究類型,是家蠶在成為標準的實驗動物過程中所必須突破的瓶頸。另外,家蠶與小鼠等經(jīng)典哺乳類模式動物相比,在外源化合物代謝動力學方面究竟存在哪些共性和差異,國內外也尚無系統(tǒng)的研究。本研究以家蠶實驗動物化的標準建設為目的,總結了家蠶實驗動物化的品種選育、飼養(yǎng)管理、設施管理等規(guī)范,設計了家蠶標準化飼養(yǎng)微屏障系統(tǒng);通過肝毒性模式藥物對乙酰氨基酚(APAP)處理,系統(tǒng)地比較研究家蠶與哺乳動物體內APAP的急性毒性分級和藥代動力學特性;通過代謝組學方法、高通量分析(RNA-Seq)方法調查APAP對家蠶內源性代謝物和基因表達的差異,揭示APAP在體內所產(chǎn)生的生物效應;用試劑盒檢測APAP染毒后家蠶催化藥物代謝關鍵酶的活性,并通過生物信息學方法分析比較家蠶與小鼠等哺乳類在這些關鍵酶進化上的差異及活性位點差異。研究獲得的主要結果如下:1.模藥APAP對家蠶的急性毒性分級、藥代動力學特征能夠為醫(yī)學實驗動物替代建立平行數(shù)據(jù)急性毒性試驗結果顯示,APAP對家蠶毒性因品種不同而表現(xiàn)出毒性敏感性不同,大造較皓月敏感。APAP處理雌、雄大造品種的LD50分別為2017±254μg/g和2169±300μg/g。急性毒性分級為中低級毒性,與哺乳類相似。代謝動力學結果表明,低濃度600μg/g劑量和高濃度3600μg/g劑量APAP在家蠶體內的藥動學呈一室開放型模型,消除半衰期(t1/2)分別為1.06h和2.77h;原藥達峰時間(tmax)分別為0.50h和1.00h;原藥達峰值濃度(Cmax)分別為67.69μg/ml和568.73μg/ml。相對生物利用度(AUC0-t)分別為:222.63 h?μg/ml和1976.32 h?μg/ml。代謝中間產(chǎn)物有N-乙酰對苯醌亞胺(NAPQI)產(chǎn)生,與哺乳類相比,藥物吸收分布、體內代謝中間產(chǎn)物、總體的動力學(PK)相似,能為醫(yī)學實驗動物替代建立平行數(shù)據(jù)。2.模藥APAP在家蠶的體內能產(chǎn)生與哺乳類共同的生物效應代謝組學分析顯示,以600μg/g劑量APAP經(jīng)口給藥家蠶8 h后,循環(huán)血中差異代謝物在三羧酸循環(huán)、糖酵解途徑、氨基酸代謝、黑色素生成等途徑中,說明APAP在體內所產(chǎn)生的毒性途徑主是因為藥物代謝過程中產(chǎn)生了氧化應激,影響了體內能量供給、物質轉運和信號傳導。代謝物差異分析發(fā)現(xiàn),APAP誘導家蠶血淋巴中氨基酸代謝產(chǎn)生差異,推測氨基酸代謝的異常和蘋果酸、琥珀酸、延胡索酸等內源代謝物的顯著下降相關,也與APAP染毒后產(chǎn)生的氧化應激相關。酪氨酸、多巴、海藻糖的顯著升高進一步證實過量的APAP導致了氧化應激的產(chǎn)生;APAP誘導家蠶的膽固醇降低,卻使β-羥基β-甲基戊二酸升高,表明APAP導致家蠶的膽固醇合成途徑失衡,甾體激素的原料供給障礙影響機體的激素調節(jié)。3.模藥APAP在家蠶的體內能產(chǎn)生與哺乳類共同的藥理作用和毒性機理RNA-Seq結果分析APAP給藥實驗組與對照組的差異基因表達顯示,在KEGG分析系統(tǒng)中與新陳代謝相關的通路里,大量的差異表達基因富集于三羧酸循環(huán)、氧化磷酸化、脂肪酸的氧化、糖酵解和糖異生等高產(chǎn)能環(huán)節(jié),從基因表達水平上進一步證明,APAP對家蠶機體的傷害,主要是氧化應激和能量代謝、物質轉運、信號傳導等途徑異常所至,這與哺乳類所產(chǎn)生的肝損傷機理一致。在KEGG分析系統(tǒng)中與有機體系統(tǒng)相關的通路里,大量的差異表達基因富集于心臟肌肉收縮、血管平滑肌收縮和調節(jié)肌動蛋白骨架等循環(huán)系統(tǒng)的相關通路,以及部分神經(jīng)元突觸基因通路,這些與代謝組學結果一致。推測APAP對家蠶具有與哺乳類相一致的抑制花生四烯酸通路的藥理作用。4.家蠶與小鼠的藥物代謝關鍵酶具有共同的活性位點和蛋白質互作機制生物信息分析結果顯示,家蠶和小鼠的谷胱甘肽轉硫酶家族成員(GSTs)在結構域和功能域方面,大多具有GSTs活性區(qū)域以及硫氧還蛋白的折疊模式;家蠶和小鼠的谷氨酸半胱氨酸連接酶催化亞基(GCLc)蛋白都具有谷胱甘肽合成酶的功能域,谷氨酸半胱氨酸連接酶(GCLM)都具有NADP依賴氧化還原酶功能域;家蠶硫氧還蛋白過氧化物酶家族(TPXs)中Jafrac1基因編碼的過氧化物酶蛋白與小鼠的Prdx1和Prdx2基因編碼的過氧化物酶具有高度保守的結構,家蠶的預測蛋白LOC733003、LOC101735759、LOC732921分別具有小鼠的Prdx3、Prdx4、Prdx5編碼蛋白的保守結構域;家蠶的2個葡萄糖醛酸轉移酶成員(UGTs)和小鼠的21個UGTs成員具有共同的尿苷二磷酸-葡萄糖醛酸和尿苷二磷酸-葡萄糖醛酸轉移酶保守功能域;家蠶和小鼠的細胞色素P450酶(CYP450)家族成員也具有CYP450保守的結構域和功能域。家蠶和小鼠的藥物代謝關鍵酶的結構與功能域上的保守性,提示兩者在主要的解毒過程與作用機理中可能存在共同的特點。5.家蠶中腸是可建立肝毒性模型的經(jīng)口給藥“首關效應”器官根據(jù)APAP經(jīng)口經(jīng)藥家蠶組織中原藥APAP、中間產(chǎn)物NAPQI分布特點,催化藥物代謝反應的關鍵酶(GST、GCL、TPX、UGT、CYP450等)的活性變化結果可知,中間產(chǎn)物經(jīng)中腸后產(chǎn)量明顯提高,高劑量APAP可造成中腸的吸收功能障礙。中腸組織中CYP450酶活變化顯著,中腸組織中GST、GCL、TPX、UGT酶活本底顯著高于脂肪體,且相應代謝酶活性變化較為顯著。表明在經(jīng)口給藥途徑中,家蠶中腸是藥物代謝的“首關效應”器官。在經(jīng)口給藥途徑中,家蠶的中腸與脂肪體相比而言,作為外源藥物的“首關效應”器官,類比哺乳類解毒器官(肝臟)更為準確。家蠶中腸是更合適的研究哺乳類肝毒性藥物毒性機理的靶器官(組織)模型。6. 結論家蠶已具備實驗動物化的基本條件,能夠建立系統(tǒng)化、標準化的實驗動物飼養(yǎng)管理、環(huán)境控制操作規(guī)范;家蠶與小鼠對肝毒性模式藥物APAP的藥物代謝動力學具有一致的特征;家蠶催化解毒作用的關鍵性代謝酶活性變化及作用機制與哺乳類相似。以家蠶為實驗動物,建立中腸損傷模型,可以作為哺乳動物肝損傷模型的替代,用于研究哺乳動物的解毒機制和肝損機理。
[Abstract]:The alternative method of experimental animals has been widely used in the field of life science. The silkworm is a Lepidoptera model insect, which has thousands of years of animal husbandry history, and has accumulated systematic and deep physiological, pathological and toxicological data. The innovation of the genetic mutation resources of the silkworm and its basic life system, material metabolism, energy metabolism and heredity. There are many similarities between mammals and mammals, which make the silkworm as the Chinese characteristic model insects are gradually developing to the model of experimental animals. However, how to realize the "experimental animals" of silkworm by systematic control of the genetic factors and the growth environment of the silkworm, how to choose the alternative according to the biological characteristics of the silkworm. The study type is the bottleneck that the silkworm must break through in the process of becoming a standard experimental animal. In addition, what are the similarities and differences in the metabolic kinetics of foreign compounds compared with the classic mammalian animal models, such as silkworm and mice, and there are no systematic studies at home and abroad. For the purpose of construction, a standardized breeding micro barrier system for silkworm, silkworm, the standardized feeding system of silkworm, was designed, and the acute toxicity classification and pharmacokinetics of APAP in silkworm and mammalian moving objects were compared and studied by the hepatotoxicity model drug (APAP). By means of metabonomics and high throughput analysis (RNA-Seq), the difference of endogenous metabolites and gene expressions of APAP in silkworm was investigated, and the biological effects of APAP in the body were revealed. The activity of the key enzyme in the catalytic drug metabolism of the silkworm in the Bombyx mori after APAP was detected by the kit, and the silkworm and mice were compared by bioinformatics. The difference in the evolution of these key enzymes and the difference in the active site of these key enzymes. The main results are as follows: the acute toxicity classification of 1. model drug APAP to the silkworm, the pharmacokinetic characteristics can be replaced by the acute toxicity test of the parallel data for the replacement of the medical experimental animals, and the toxicity of APAP to the silkworm is different. The sensitivity was different, and the.APAP treatment was more sensitive than that of the white moon. The LD50 of the male species was 2017 + 254 g/g and 2169 + 300 g/g. respectively. The acute toxicity of the male was similar to the mammalian. The metabolic kinetics showed that the pharmacokinetics of the low concentration 600 mu g/g and the high concentration of 3600 micron g/g in the silkworm was open in one room. The elimination half life (t1/2) was 1.06h and 2.77h, respectively, and the peak time (Tmax) of the original drug was 0.50h and 1.00h respectively; the peak concentration (Cmax) of the original drug was 67.69 mu g/ml and 568.73 micron relative bioavailability (AUC0-t) respectively: 222.63 h, micron and 1976.32? Compared with milk, the drug absorption distribution, metabolic intermediate products in the body, and the overall dynamics (PK) are similar. It can replace the parallel data.2. model drug APAP for the medical experimental animals to produce the common biological effect metabolomics analysis in the silkworm in the silkworm, and the difference generation in the circulating blood after the 8 h of the Bombyx Mori was given to the Bombyx mori with the dose of 600 mu g /g. The metabolites in the three carboxylic acid cycle, glycolysis pathway, amino acid metabolism, melanogenesis, etc., indicate that the toxic pathways produced by APAP in the body are mainly caused by oxidative stress during the metabolic process, affecting the energy supply, transport and signal transduction in the body. The analysis of metabolite differences found that APAP induces ammonia in the haemolymph of silkworm. Differences in basal acid metabolism suggest that abnormality in amino acid metabolism is associated with a significant decline in endogenous metabolites such as malic acid, succinic acid and Corydalis, and also associated with oxidative stress produced by APAP. A significant increase in tyrosine, DOPA and trehalose further confirms that excessive APAP leads to oxidative stress; APAP induces silkworm gall. The decrease of sterol and the increase of beta hydroxy beta methylglutaric acid indicates that APAP leads to the imbalance of cholesterol synthesis pathway in silkworm, steroid hormone supply barrier affects the hormone regulation of the body's hormone regulation.3. model drug APAP can produce the common pharmacological action and toxic mechanism of mammalian in the silkworm in the body of the silkworm, RNA-Seq results analysis of the APAP administration experiment group and the pair The difference gene expression in the group showed that in the KEGG analysis system, a large number of differentially expressed genes were enriched in the three carboxylic acid cycle, oxidative phosphorylation, fatty acid oxidation, glycolysis and sugar isogenesis, and further demonstrated that the damage to silkworm organism by APAP is mainly oxygen from the gene expression level. In the KEGG analysis system associated with the organism system, a large number of differentially expressed genes are enriched in cardiac muscle contraction, vascular smooth muscle contraction, and actin framework regulation. Related pathways and partial neuronal synaptic gene pathways, which are consistent with the results of metabolomics. It is speculated that APAP has the pharmacological action of inhibiting the four enoic acid pathway of the silkworm, which is consistent with mammalian,.4., the key enzyme of the drug metabolism of the silkworm and mice, has the common active site and protein interaction mechanism bioinformatics analysis results. The family members of the glutathione transferase family (GSTs) in the silkworm and mouse showed that most of the domain and functional domain had the GSTs active region and the folding pattern of thioredoxin; the glutamate cysteine ligase catalyzed subunit (GCLc) protein of the silkworm and mice all had the functional domain of the glutathione synthetase, and the glutamate cysteine linkage The enzyme (GCLM) has NADP dependent oxidoreductase function domain; the peroxidase protein encoded by the Jafrac1 gene in the silkworm thioredoxin peroxidase family (TPXs) has a highly conserved structure with the peroxidase encoded by the Prdx1 and Prdx2 genes in mice, and the predicted protein LOC733003, LOC101735759, and LOC732921 of the silkworm are respectively of the silkworm. The conservative domain of Prdx3, Prdx4, Prdx5 encoded proteins in mice; 2 members of glucuronotransferase (UGTs) in silkworm and 21 UGTs members of mice have the same conservative domain of uridine two phosphoric acid glucuronic acid and uridine two phosphate glucuronide transferase; the family of cytochrome P450 enzyme (CYP450) family in silkworm and mice is also a member of the family. CYP450 conserved domain and functional domain. The structure and conservatism of the key enzymes in the drug metabolism of the silkworm and mice, suggesting that both of them may have the common characteristics in the main detoxification process and the mechanism of action.5. the middle intestine of the silkworm, silkworm, is the "first effect" organ of the oral administration of the liver toxicity model based on the mouth of the APAP The distribution of central product APAP, intermediate product NAPQI, the activity changes of the key enzymes (GST, GCL, TPX, UGT, CYP450, etc.) in the drug metabolism reaction of the Bombyx mori tissue, the output of the intermediate products obviously increased after the midgut, and the high dose of APAP could cause the absorption dysfunction of the midgut. The change of the CYP450 enzyme activity in the midgut tissue was significant and the middle intestinal tissue was in the middle intestine. The GST, GCL, TPX, UGT enzyme activity was significantly higher than that of the fat body, and the activity of the corresponding metabolic enzyme changed significantly. It showed that in the oral administration route, the middle intestine of the silkworm was the "first effect" organ of the drug metabolism. Mammalian detoxification organ (liver) is more accurate. Silkworm midgut is a more suitable target organ (tissue) model to study the toxicity mechanism of mammalian toxic drugs to the liver.6. conclusion silkworm has the basic conditions for experimental animals. It can establish systematized, standardized experimental animal feeding management, environmental control operation norms, silkworm and mice to liver. The metabolic kinetics of the toxic model drug APAP has the same characteristics. The changes in the activity of the key metabolic enzymes and the mechanism of action of the silkworm are similar to those of mammalian. The model of midgut injury is established by the silkworm as the experimental animal, which can be used as a substitute for the model of mammalian liver injury and is used to study the detoxification mechanism of mammals. And the mechanism of liver damage.
【學位授予單位】：蘇州大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R-332
本文編號：2125778
[Abstract]:The alternative method of experimental animals has been widely used in the field of life science. The silkworm is a Lepidoptera model insect, which has thousands of years of animal husbandry history, and has accumulated systematic and deep physiological, pathological and toxicological data. The innovation of the genetic mutation resources of the silkworm and its basic life system, material metabolism, energy metabolism and heredity. There are many similarities between mammals and mammals, which make the silkworm as the Chinese characteristic model insects are gradually developing to the model of experimental animals. However, how to realize the "experimental animals" of silkworm by systematic control of the genetic factors and the growth environment of the silkworm, how to choose the alternative according to the biological characteristics of the silkworm. The study type is the bottleneck that the silkworm must break through in the process of becoming a standard experimental animal. In addition, what are the similarities and differences in the metabolic kinetics of foreign compounds compared with the classic mammalian animal models, such as silkworm and mice, and there are no systematic studies at home and abroad. For the purpose of construction, a standardized breeding micro barrier system for silkworm, silkworm, the standardized feeding system of silkworm, was designed, and the acute toxicity classification and pharmacokinetics of APAP in silkworm and mammalian moving objects were compared and studied by the hepatotoxicity model drug (APAP). By means of metabonomics and high throughput analysis (RNA-Seq), the difference of endogenous metabolites and gene expressions of APAP in silkworm was investigated, and the biological effects of APAP in the body were revealed. The activity of the key enzyme in the catalytic drug metabolism of the silkworm in the Bombyx mori after APAP was detected by the kit, and the silkworm and mice were compared by bioinformatics. The difference in the evolution of these key enzymes and the difference in the active site of these key enzymes. The main results are as follows: the acute toxicity classification of 1. model drug APAP to the silkworm, the pharmacokinetic characteristics can be replaced by the acute toxicity test of the parallel data for the replacement of the medical experimental animals, and the toxicity of APAP to the silkworm is different. The sensitivity was different, and the.APAP treatment was more sensitive than that of the white moon. The LD50 of the male species was 2017 + 254 g/g and 2169 + 300 g/g. respectively. The acute toxicity of the male was similar to the mammalian. The metabolic kinetics showed that the pharmacokinetics of the low concentration 600 mu g/g and the high concentration of 3600 micron g/g in the silkworm was open in one room. The elimination half life (t1/2) was 1.06h and 2.77h, respectively, and the peak time (Tmax) of the original drug was 0.50h and 1.00h respectively; the peak concentration (Cmax) of the original drug was 67.69 mu g/ml and 568.73 micron relative bioavailability (AUC0-t) respectively: 222.63 h, micron and 1976.32? Compared with milk, the drug absorption distribution, metabolic intermediate products in the body, and the overall dynamics (PK) are similar. It can replace the parallel data.2. model drug APAP for the medical experimental animals to produce the common biological effect metabolomics analysis in the silkworm in the silkworm, and the difference generation in the circulating blood after the 8 h of the Bombyx Mori was given to the Bombyx mori with the dose of 600 mu g /g. The metabolites in the three carboxylic acid cycle, glycolysis pathway, amino acid metabolism, melanogenesis, etc., indicate that the toxic pathways produced by APAP in the body are mainly caused by oxidative stress during the metabolic process, affecting the energy supply, transport and signal transduction in the body. The analysis of metabolite differences found that APAP induces ammonia in the haemolymph of silkworm. Differences in basal acid metabolism suggest that abnormality in amino acid metabolism is associated with a significant decline in endogenous metabolites such as malic acid, succinic acid and Corydalis, and also associated with oxidative stress produced by APAP. A significant increase in tyrosine, DOPA and trehalose further confirms that excessive APAP leads to oxidative stress; APAP induces silkworm gall. The decrease of sterol and the increase of beta hydroxy beta methylglutaric acid indicates that APAP leads to the imbalance of cholesterol synthesis pathway in silkworm, steroid hormone supply barrier affects the hormone regulation of the body's hormone regulation.3. model drug APAP can produce the common pharmacological action and toxic mechanism of mammalian in the silkworm in the body of the silkworm, RNA-Seq results analysis of the APAP administration experiment group and the pair The difference gene expression in the group showed that in the KEGG analysis system, a large number of differentially expressed genes were enriched in the three carboxylic acid cycle, oxidative phosphorylation, fatty acid oxidation, glycolysis and sugar isogenesis, and further demonstrated that the damage to silkworm organism by APAP is mainly oxygen from the gene expression level. In the KEGG analysis system associated with the organism system, a large number of differentially expressed genes are enriched in cardiac muscle contraction, vascular smooth muscle contraction, and actin framework regulation. Related pathways and partial neuronal synaptic gene pathways, which are consistent with the results of metabolomics. It is speculated that APAP has the pharmacological action of inhibiting the four enoic acid pathway of the silkworm, which is consistent with mammalian,.4., the key enzyme of the drug metabolism of the silkworm and mice, has the common active site and protein interaction mechanism bioinformatics analysis results. The family members of the glutathione transferase family (GSTs) in the silkworm and mouse showed that most of the domain and functional domain had the GSTs active region and the folding pattern of thioredoxin; the glutamate cysteine ligase catalyzed subunit (GCLc) protein of the silkworm and mice all had the functional domain of the glutathione synthetase, and the glutamate cysteine linkage The enzyme (GCLM) has NADP dependent oxidoreductase function domain; the peroxidase protein encoded by the Jafrac1 gene in the silkworm thioredoxin peroxidase family (TPXs) has a highly conserved structure with the peroxidase encoded by the Prdx1 and Prdx2 genes in mice, and the predicted protein LOC733003, LOC101735759, and LOC732921 of the silkworm are respectively of the silkworm. The conservative domain of Prdx3, Prdx4, Prdx5 encoded proteins in mice; 2 members of glucuronotransferase (UGTs) in silkworm and 21 UGTs members of mice have the same conservative domain of uridine two phosphoric acid glucuronic acid and uridine two phosphate glucuronide transferase; the family of cytochrome P450 enzyme (CYP450) family in silkworm and mice is also a member of the family. CYP450 conserved domain and functional domain. The structure and conservatism of the key enzymes in the drug metabolism of the silkworm and mice, suggesting that both of them may have the common characteristics in the main detoxification process and the mechanism of action.5. the middle intestine of the silkworm, silkworm, is the "first effect" organ of the oral administration of the liver toxicity model based on the mouth of the APAP The distribution of central product APAP, intermediate product NAPQI, the activity changes of the key enzymes (GST, GCL, TPX, UGT, CYP450, etc.) in the drug metabolism reaction of the Bombyx mori tissue, the output of the intermediate products obviously increased after the midgut, and the high dose of APAP could cause the absorption dysfunction of the midgut. The change of the CYP450 enzyme activity in the midgut tissue was significant and the middle intestinal tissue was in the middle intestine. The GST, GCL, TPX, UGT enzyme activity was significantly higher than that of the fat body, and the activity of the corresponding metabolic enzyme changed significantly. It showed that in the oral administration route, the middle intestine of the silkworm was the "first effect" organ of the drug metabolism. Mammalian detoxification organ (liver) is more accurate. Silkworm midgut is a more suitable target organ (tissue) model to study the toxicity mechanism of mammalian toxic drugs to the liver.6. conclusion silkworm has the basic conditions for experimental animals. It can establish systematized, standardized experimental animal feeding management, environmental control operation norms, silkworm and mice to liver. The metabolic kinetics of the toxic model drug APAP has the same characteristics. The changes in the activity of the key metabolic enzymes and the mechanism of action of the silkworm are similar to those of mammalian. The model of midgut injury is established by the silkworm as the experimental animal, which can be used as a substitute for the model of mammalian liver injury and is used to study the detoxification mechanism of mammals. And the mechanism of liver damage.
【學位授予單位】：蘇州大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R-332
【參考文獻】
相關期刊論文 前10條
1 肖麗蓉;張友洪;周安蓮;肖文福;肖金樹;楊文娟;李方方;;外源海藻糖對家蠶生長和繭絲品質的影響[J];安徽農(nóng)業(yè)科學;2012年03期
2 祝新榮,何克榮,柳新菊;家蠶性別控制種質資源庫的構建與利用[J];蠶桑通報;2005年03期
3 ;基因組研究為何選中家蠶為“代表生物”?[J];蠶學通訊;2004年01期
4 夏安扣;農(nóng)藥“殺蟲雙”對家蠶毒性的試驗[J];蠶業(yè)科學;1981年03期
5 魯興萌,吳勇軍;吡蟲啉對家蠶的毒性[J];蠶業(yè)科學;2000年02期
6 張志芳,魏兆軍,方琴琴,劉淑青,林昌麒;家蠶品種資源主要經(jīng)濟性狀特點的研究[J];蠶業(yè)科學;2000年03期
7 張月華,徐安英,李木旺,侯成香,孫平江;家蠶品種資源數(shù)據(jù)庫的構建[J];蠶業(yè)科學;2004年03期
8 司樹鼎;王開運;林榮華;馬惠;李元濤;;25種農(nóng)藥對家蠶的毒性評價和中毒癥狀觀察[J];蠶業(yè)科學;2007年03期
9 秦儉;袁聯(lián)偉;;我國家蠶基因組的最新研究——對家蠶基因組精細圖和40個蠶類基因組遺傳變異圖的解讀[J];蠶業(yè)科學;2010年01期
10 江坤榮，陳長樂，，孫宏偉;稻虱凈對家蠶毒性和安全性評估[J];蠶業(yè)科學;1994年02期
相關博士學位論文 前2條
1 楊亦樺;棉鈴蟲對擬除蟲菊酯氧化代謝抗性的生化與分子機理[D];南京農(nóng)業(yè)大學;2005年
2 艾均文;家蠶（Bombyx mori）全基因組細胞色素P450基因結構與進化分析及CYP18A1克隆與功能研究[D];西南大學;2008年
相關碩士學位論文 前2條
1 魏廣兵;抗結核藥物異煙肼（INH）引起家蠶氧化損傷的機制研究[D];蘇州大學;2013年
2 徐旭;酰胺類模藥APAP在家蠶體內的代謝途徑研究[D];蘇州大學;2013年
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