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1.
Zearalenone (ZEA) as a mycoestrogen is found frequently in human foods and animal feeds. Its estrogenic effects depend on its biotransformation fate including both first- and second-phase reactions, which are predominantly governed by hydroxylation and glucuronidation, respectively. In this study, we investigate the hepatic biotransformation of ZEA in river buffalo. To evaluate the hepatic biotransformation of ZEA, both subcellular fractions of the liver were prepared. ZEA was incubated with intracellular subfractions in the presence of nicotinamide dinucleotide phosphate, and the products were determined by means of high-performance liquid chromatography. Moreover, in the same frame of experiment and in the presence of uridine diphosphate glucuronic acid, the rate of glucuronidation for substrate and products were estimated as well. We found that α-zearalenol (α-ZOL) is the major hydroxylated hepatic metabolite of ZEA produced by both studied subcellular fractions. The enzymatic kinetics analyses indicated that the α-ZOL and β-ZOL production by microsomal fraction were two- and three-fold higher than those by postmitochondrial fraction, respectively. The calculated data showed that α-ZOL is conjugated with glucuronic acid more than ZEA and β-ZOL, especially at the lower concentrations, which seems to be more applicable. Our data suggest that unlike other domestic ruminants including cattle and sheep, the hepatic biotransformation of ZEA in river buffalo results in bioactivation and formation of potent estrogenic metabolite. Moreover, at the relevant concentrations, the produced potent estrogenic metabolite is entirely conjugated with glucuronic acid and, consequently, may cause the prolongation of presence of the compound in the body due to enterohepatic cycle.  相似文献   

2.
This study reports fluorescence high performance liquid chromatography (HPLC) and UV-Vis HPLC methods for the determination of 7-ethoxyresorufin O-deethylase (EROD) and tolbutamide methylhydroxylase (TMH) activities, respectively, using bovine liver microsomes. The detection limits were 0.022 and 5.5 pmol on the column, respectively; intra-day and inter-day precisions (expressed as relative standard deviation) were <10%. Both methods showed enough sensitivity to allow for an accurate determination of enzyme kinetic parameters according to Michaelis-Menten plots and the results were: K(m)=0.23+/-0.051 microM, V(max)=0.488+/-0.035 nmol/min/mg protein for EROD activity, and K(m)=1010+/-155.7 microM, V(max)=0.089+/-0.006 nmol/min/mg protein for TMH activity. An Eadie-Hofstee plot analysis showed that in bovine liver microsomes, EROD and TMH activities followed a monophasic kinetic pattern. alpha-Naphthoflavone, a cytochrome P450 1A1/2 (CYP1A1/2) inhibitor, and sulfaphenazole, a cytochrome P450 2C9 (CYP2C9) inhibitor, decreased EROD and TMH activities, respectively. The sensitivity of the methods allowed the use of microsomes with low enzyme activity, such as those from veal calf liver. Thus, EROD and TMH activities may be adopted as markers for the evaluation of CYP1A and CYP2C9-like activities in liver microsomes from veal and beef cattle.  相似文献   

3.
Flubendazole (FLBZ) is a broad‐spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl‐reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red‐FLBZ). The rate of microsomal red‐FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red‐FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red‐FLBZ to FLBZ in a NADP+‐dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red‐FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species.  相似文献   

4.
1. Diets with increasing proportions of Fusarium-toxin-contaminated wheat were fed to Pekin ducks for 49 d in order to titrate the lowest effect level. Dietary deoxynivalenol (DON) and zearalenone (ZON) concentrations were successively increased up to 6 to 7 mg/kg and 0.05 to 0.06 mg/kg, respectively. 2. Feed intake, live weight gain and feed to gain ratio were not influenced by dietary treatment. 3. Gross macroscopic inspection of the upper digestive tract did not reveal any signs of irritation, inflammation or other pathological changes. The weight of the bursa of Fabricius, relative to live weight, decreased in a dose-related fashion. Activities of glutamate dehydrogenase and gamma-glutamyl-transferase in serum were either unaffected or inconsistently affected by dietary treatments. 4. Concentrations of DON and of its de-epoxydised metabolite in plasma and bile were lower than the detection limits of 6 and 16 ng/ml, respectively, of the applied high performance liquid chromatography (HPLC) method. 5. ZON or its metabolites were not detectable in plasma and livers (detection limits of the HPLC method were 1, 0.5 and 5 ng/g for ZON, alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL), respectively). Concentrations of ZON, alpha-ZOL and beta-ZOL in bile increased linearly with dietary ZON concentration. The mean proportions of ZON, alpha-ZOL and beta-ZOL of the sum of all three metabolites were 80, 16 and 4%, respectively. 6. Taken together, it can be concluded that dietary DON and ZON concentrations up to 6 and 0.06 mg/kg, respectively, did not adversely affect performance and health of growing Pekin ducks.  相似文献   

5.
By studying carcass quality, expressed as affection, pathological findings, slaughter-weight and evaluation, a picture of an animal's health and potential as high quality food is achieved. This study compares the carcass quality in Swedish certified organic meat production with that of conventional meat production slaughtered during 1997. The study involves 3.9 million pigs, about 570,000 cattle and 190,000 sheep, all reared conventionally and 3483 pigs 4949 cattle and 4997 sheep reared according to organic standards. Pathological and additional findings are registered by meat inspectors from the Swedish National Food Administration at the post-mortem inspection. There was a significant difference at the post-mortem inspection of growing-fattening pigs; 28% of conventionally and 17% of the organically reared pigs had one or more registered lesion. The carcass evaluation of swine shows a higher meat percentage in conventional swine production. The total rate of registered abnormalities in cattle was systems around 28% from organic and 27% from conventionally reared herds. Carcass evaluation of cattle from organic herds gave higher classification in the EUROP system, whereas the fat content was lower than that of conventionally reared cattle. Sheep, reared both organically and conventionally, showed a lower rate of registered abnormalities than swine and cattle.  相似文献   

6.
Moxidectin is an antiparasitic drug widely used in cattle, sheep and companion animals. No data were available on its metabolism in wild species or in monogastrics. The in vitro metabolism of 14C-moxidectin was studied using hepatic microsomes from several different species: cow (Bos taurus), sheep (Ovis ovis), goat (Capra hircus), deer (Cervus dama), rat (Rattus norvegicus), pig (Sus scrofa and rabbit (Oryctolagus cuniculus). After separation and quantification by HPLC, the extent of metabolism of 14C-moxidectin was greatest with microsomes from sheep (32.7%) as compared to those from cows (20.6%), deer (15.4%), goats (12.7%), rabbits (7.0%) or rats (3.0%). The least metabolism occurred with microsomes from pigs, with 0.8% of total detected metabolites. A C29 monohydroxymethyl metabolite was detected in the greatest amounts, providing 0.4% out of the total detected radioactivity in pigs and 19.3% in sheep. In addition, the importance of P450 3A in the metabolism of 14C-moxidectin was confirmed by using in vivo induced P450 in combination with various P450 inhibitors.  相似文献   

7.
Laurincik, J., L. Kolodzieyski, V. Elias, P. Hyttel, Y. Osawa, A. Sirotkin: Immunocytochemical localization of aromatase in the ovary of superovulated cattle, pigs and sheep. Acta vet. scand. 1994, 35, 185-191.–The localization of aromatase, an enzyme converting androgens to estrogen, in the ovaries of superovulated cattle, pigs and sheep was studied immunocytochemically in the preovulatory and postovulatory period using anti-human placental aromatase cytochrome P-450 antiserum. Immunostaining for aromatase was detected in the granulosa cells of preovulatory follicles of all species studied. Theca interna cells were stained in preovulatory follicles in the pig but not in cattle and sheep. Interstitial gland cells, cumulus cells and oocytes were unstained in all species. In cattle and pig the corpora lutea were unstained whereas they displayed staining in the sheep. Preantral and small antral follicles were unstained during both the preovulatory and postovulatory period in all species.It is concluded that granulosa cells of preovulatory follicles are the main residence for aromatase activity in superovulated cattle, pig and sheep, whereas the activity of theca interna and corpora lutea is species specific.  相似文献   

8.
Monepantel (MNP) is a new amino‐acetonitrile derivative anthelmintic drug used for the treatment of gastrointestinal (GI) nematodes in sheep. The present work investigated the main enzymatic pathways involved in the hepatic biotransformation of MNP in sheep and cattle. The metabolic stability in ruminal fluid of both the parent drug and its main metabolite (monepantel sulphone, MNPSO2) was characterized as well. Additionally, the relative distribution of both anthelmintic molecules between the fluid and particulate phases of the ruminal content was studied. Liver microsomal fractions from six (6) rams and five (5) steers were incubated with a 40 μm of MNP. Heat pretreatment (50 °C for 2 min) of liver microsomes was performed for inactivation of the flavin‐monooxygenase (FMO) system. Additionally, MNP was incubated in the presence of 4, 40, and 80 μm of methimazole (MTZ), a FMO inhibitor, or equimolar concentrations of piperonyl butoxide (PBx), a well‐known general cytochrome P450 (CYP) inhibitor. In both ruminant species, MNPSO2 was the main metabolite detected after MNP incubation with liver microsomes. The conversion rate of MNP into MNPSO2 was fivefold higher (< 0.05) in sheep (0.15 ± 0.08 nmol/min·mg) compared to cattle. In sheep, the relative involvement of both FMO and CYP systems (FMO/CYP) was 36/64. Virtually, only the CYP system appeared to be involved in the production of MNPSO2 in cattle liver. Methimazole significantly reduced (41 to 79%) the rate of MNPSO2 production in sheep liver microsomes whereas it did not inhibit MNP oxidation in cattle liver microsomes. On the other hand, PBx inhibited the production of MNPSO2 in liver microsomes of both sheep (58 to 98%, in a dose‐dependent manner) and cattle (almost 100%, independently of the PBx concentration added). The incubation of MNP and MNPSO2 with ruminal contents of both species showed a high chemical stability without evident metabolism and/or degradation as well as an extensive degree of adsorption (83% to 90%) to the solid phase of the ruminal content. Overall, these results are a further contribution to the understanding of the metabolic fate of this anthelmintic drug in ruminants.  相似文献   

9.
The highest prevalences and intensities of human fasciolosis by Fasciola hepatica are found in the northern Bolivian Altiplano, where sheep and cattle are the main reservoir host species and pigs and donkeys the secondary ones. Morphometric comparisons of many linear measurements, areas and ratios of F. hepatica adults (from sheep, cattle and pigs) and eggs (from sheep, cattle, pigs and donkeys) in natural liver fluke populations of the Bolivian Altiplano, as well as of F. hepatica adults and eggs experimentally obtained in Wistar rats infected with Altiplanic sheep, cattle and pig isolates, were made using computer image analysis and an allometric model. Although morphometric values of adult flukes from natural populations of sheep, cattle, and pigs showed great overlap, there were clear differences in allometric growth. The allometries analyzed were: body area (BA) versus body length (BL), BA versus body width (BW), BA versus perimeter (Pe), BA versus distance between posterior end of body and ventral sucker (P-VS), BL versus BW, BL versus Pe, and BL versus P-VS. These allometries show a good fit in the seven pairs of variables in all the populations examined. Comparative statistical analysis of the allometries shows that fluke adult populations from sheep, cattle and pigs significantly differ in BL versus BW and BL versus P-VS functions. Statistical analysis of F. hepatica egg size shows characteristic morphometric traits in each definitive host species. In experimentally infected rats, fluke adult allometry and egg morphometry do not vary depending on the Altiplanic definitive host species isolate. Our study reveals that the definitive host species decisively influences the size of F. hepatica adults and eggs, and these influences do not persist in a rodent definitive host model.  相似文献   

10.
Use of the immunosuppressant mycophenolic acid (MPA) in cats is limited because MPA elimination depends on glucuronidation, which is deficient in cats. We evaluated formation of major (phenol glucuronide) and minor (acyl glucuronide, phenol glucoside, and acyl glucoside) MPA metabolites using liver microsomes from 16 cats, 26 dogs, and 48 humans. All MPA metabolites were formed by human liver microsomes, while dog and cat liver microsomes formed both MPA glucuronides, but only one MPA glucoside (phenol glucoside). Intrinsic clearance (CLint) of MPA for phenol glucuronidation by cat liver microsomes was only 15–17% that of dog and human liver microsomes. However, CLint for acyl glucuronide and phenol glucoside formation in cat liver microsomes was similar to or greater than that for dog and human liver microsomes. While total MPA conjugation CLint was generally similar for cat liver microsomes compared with dog and human liver microsomes, relative contributions of each pathway varied between species with phenol glucuronidation predominating in dog and human liver microsomes and phenol glucosidation predominating in cat liver microsomes. MPA conjugation variation between cat liver microsomes was threefold for total conjugation and for phenol glucosidation, sixfold for phenol glucuronidation, and 11‐fold for acyl glucuronidation. Our results indicate that total MPA conjugation is quantitatively similar between liver microsomes from cats, dogs, and humans despite large differences in the conjugation pathways that are utilized by these species.  相似文献   

11.
1. Diets with increasing proportions of Fusarium toxin-contaminated wheat (0, 170, 340 and 510 g CW/kg) were fed to male turkeys (BUT Big 6) from d 21 to d 56 of age. Each diet was tested with or without a non-starch-polysaccharide (NSP) hydrolysing enzyme preparation. Dietary deoxynivalenol (DON) and zearalenone (ZON) concentrations were successively increased up to approximately 5.4 and 0.04 mg/kg, respectively. 2. Weight gain decreased slightly with increasing proportions of CW, by 1.6, 0.7 and 3.6%, whereas other performance parameters remained unaffected. NSP enzyme supplements to the diets had no influence. 3. The weight of the emptied jejunum plus ileum, relative to live weight, decreased in a dose-related fashion whereby the NSP enzyme exerted an additional weight-decreasing effect. A similar weight-decreasing NSP enzyme effect was noted for heart weights. Activity of glutamate dehydrogenase in serum was significantly increased in groups fed the diets with the highest CW proportion, whereas gamma-glutamyl-transferase remained unaltered. 4. Viscosity in the small intestine was significantly reduced by supplementing the diets with the NSP enzyme. This effect successively decreased with increasing proportions of the CW. 5. Concentrations of DON and of its de-epoxidised metabolite de-epoxy-DON in plasma, liver and breast meat were lower than the detection limits of 2 ng/ml (plasma) and 4 ng/g, respectively, of the applied HPLC method. DON concentration in bile reached up to 13 to 23 ng/ml whereas de-epoxy-DON concentration was lower than 4 ng/ml. 6. ZON or its metabolites were not detectable in plasma, liver or breast meat (detection limits of the HPLC method were 1, 0.5 and 5 ng/g for ZON, alpha-zearalenol (ZOL) and beta-ZOL, respectively). Concentrations of ZON and alpha-ZOL in bile increased with dietary ZON concentration. The mean proportions of ZON, alpha-ZOL and beta-ZOL of the sum of all three metabolites were 19, 77 and 4%, respectively.  相似文献   

12.
Virkel, G., Carletti, M., Cantiello, M., Della Donna, L., Gardini, G., Girolami, F., Nebbia, C. Characterization of xenobiotic metabolizing enzymes in bovine small intestinal mucosa. J. vet. Pharmacol. Therap. 33 , 295–303. The intestinal mucosa plays a capital role in dictating the bioavailability of a large array of orally ingested drugs and toxicants. The activity and the expression of several xenobiotic metabolizing enzymes were measured in subcellular fractions from the duodenal mucosa of male veal calves and beef cattle displaying a functional rumen but differing in both age (about 8 months vs. 18 to 24 months) and dietary regimens (i.e., milk replacer plus hay and straw vs. corn and concentrated meal). Intestinal microsomes showed cytochrome P450 (CYP) 2B, 2C‐ and 3A‐mediated activities and the presence of the corresponding immunorelated proteins, but no proof of CYP1A expression and/or functions could be provided. Intestinal microsomes were also active in performing reactions typically mediated by carboxylesterases (indophenylacetate hydrolysis), flavin‐containing monooxygenases (methimazole S‐oxidation), and uridindiphosphoglucuronyltransferases (1‐naphthol glucuronidation), respectively. Cytosolic fractions displayed the glutathione S‐transferase (GST)‐dependent conjugation of 1‐chloro‐2,4‐dinitrobenzene; besides, the GST‐mediated conjugation of ethacrinic acid (GSTπ) or cumene hydroperoxide (GSTα) was matched by the presence of the corresponding immunorelated proteins. Conversely, despite the lack of measurable activity with 3,4‐dichloronitrobenzene, a protein cross reacting with anti‐rat GSTμ antibodies could be clearly detected. Although, as detected by densitometry, CYPs and GST isoenzymes tended to be more expressed in beef cattle than in veal calf preparations, there was a general poor correlation with the rate of the in vitro metabolism of the selected diagnostic probes.  相似文献   

13.
The development of efficient ovarian preantral follicle (PF) isolation and culture systems provide a large number of oocytes for the manipulation and embryo production. It also helps for understanding the mechanisms of follicle and oocyte development. Isolation and culture protocols for PFs were developed for many domestic species like cattle, buffalo, sheep, goat, pig, horse, camel, dog and cats; however, embryo production from oocytes derived from in vitro grown PFs was reported only in pigs, buffalo, sheep and goat. The rate of oocyte maturation from PFs grown in vitro is low and requires considerable research. This paper presents an overview of isolation and culture systems of PFs that have been developed for domestic species (cattle, buffalo, sheep, goat, pigs, horse, camel, dog and cat) along with the current status of progress achieved in the direction of producing embryos using PFs as the source of oocyte in these species.  相似文献   

14.
Bioactivation of zearalenone by porcine hepatic biotransformation   总被引:1,自引:0,他引:1  
Zearalenone (ZEA) is a resorcylic acid lactone derivative produced by various Fusarium species that are widely found in food and feeds. The structure of zearalenone is flexible enough to allow a conformation able to bind to mammalian oestrogen receptors, where it acts as an agonist. Using oestrogen-dependent Human Breast Cancer (MCF-7) cells, the oestrogenic activity of zearalenone and its derivatives were compared using 17 beta-oestradiol as a positive control. The results obtained demonstrate that the oestrogenic potency of ZEA derivatives could be ranked in the following order: alpha-zearalenol > alpha-zearalanol > zearalenone > beta-zearalenol. Since pigs have been reported to be among the most sensitive animal species, biotransformation studies with pig liver subcellular fractions were conducted. These studies indicated that alpha-zearalenol is the main hepatic metabolite of zearalenone in pigs, and it is assumed that 3 alpha- and 3 beta-hydroxysteroid dehydrogeneases are involved in the hepatic biotransformation, since the formation of alpha-zearalenol and beta-zearalenol could be inhibited by prototypic substrates for either enzyme. The bioactivation of ZEA into the more active alpha-zearalenol seems to provide a possible explanation for the observed high sensitivity of pigs towards feeding-stuffs contaminated with the mycotoxin.  相似文献   

15.
The pharmacokinetics of amoxicillin (Amx) were determined in pigs following intravenous (IV) administration of a single dose of 15 mg/kg and a single dose of 15 mg/kg of a new oral formulation (Amx-FP containing 10% amoxicillin). Residue studies were performed to determine residues in edible tissues of healthy pigs after chronic oral administration of Amx-FP at a daily dose of 15 mg/kg for five consecutive days. After IV administration, the plasma concentration was characteristic of a two-compartment open model. The main pharmacokinetic variables were: t(1/2lambda(n)), MRT=90.1 min, V(darea)=0.81 L/kg and Cl(b)=3.9 mL/kg/min. After single oral administration the main pharmacokinetic variables were: C(max)=758 mug/L, t(max)=347 min and Cl(b/f)=3.7 mL/kg/min for Amx-FP. The oral bioavailability (F) was calculated at 11% for Amx-FP. Based on maximum residue levels (MRL) for AMX in pigs established at 50 microg/kg for all tissues, the withdrawal times of AMX in muscle and skin plus fat were estimated (95% tolerance limit and 95% confidence) to fall below the MRL after a withdrawal period of seven days. Levels of AMX in the liver and kidneys were estimated to fall below the MRL after a withdrawal period of four days.  相似文献   

16.
An outbreak of foot and mouth disease (FMD) due to SAT2 occurred among cattle, sheep and pigs in C?te-d'Ivoire. The morbidity and mortality were low so vaccination of only high value livestock in intensive production systems was suggested.  相似文献   

17.

Bovine herpesvirus 1 (BoHV1) is the cause of economically significant viral infections in cattle. Respiratory symptoms associated with the infection are known as Infectious Bovine Rhinotracheitis (IBR). Sheep and goats are less sensitive to the infection although their role in inter-species viral transmission under field conditions is subject to controversy. The objective of this study was to investigate seroprevalence of BoHV1 infections in cattle, sheep, and goats raised together for at least a year. Blood serum samples were taken from 226 cattle, 1.053 sheep, and 277 goats from 17 small- to medium-scale farms. BoHV1-specific antibody presence and titers were determined using virus neutralization test. In total, 73 of the 226 cattle (32.3%) were seropositive. The infection was detected in 13 of the 17 farms. Infection rates ranged from 5.8 to 88.8%. Only one of the 1053 sheep (0.09%) was seropositive. However, 58 of the 277 (20.9%) goats were seropositive. Goat samples taken from 8 of the 17 farms were seropositive with infection rates ranging from 17 to 38.9%. Statistical analysis showed a significant correlation in infection rates between cattle and goats but not sheep. These results suggest that goats may be more sensitive to the BHV1 infection than sheep and the role of goats as possible reservoirs for BoHV1 in the control and eradication of BHV1 in cattle should be considered in future studies.

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18.
A study of growth gradients of the limbs and axial skeleton was carried out in cattle, sheep and pigs, with the aid of gross anatomical dissection. The comparative study is discussed relative to each individual species and to interspecies differences.  相似文献   

19.
A total of 288 serum samples were collected from 12 species of animals in various localities of Japan from 1975 to 1977. Neutralizing antibody to bovine rotavirus was found in serum samples from all the species, viz., horses, cattle, sheep, goats, pigs, dogs, rabbits, guinea pigs, rats, mice, chickens and human beings. The incidence of neutralizing antibody in titers of 1 : 2 or higher ranged from 31 to 100%, and high incidences exceeding 70% were obtained in horses, cattle, sheep, pigs, dogs, rabbits and human beings. High titers were most common in horses, cattle, sheep and pigs. These serological results suggest that rotaviruses occur commonly in these species of animals.  相似文献   

20.
The subcellular distribution of beta-carotene, retinol, and alpha-tocopherol in lymphocytes was studied in pigs (50 to 55 kg) injected once with 0, 20, or 40 mg of beta-carotene. Blood was sampled at 0, 24, 48, and 72 h postinjection. Plasma beta-carotene in treated pigs peaked at 24 h and decreased rapidly thereafter. Beta-carotene was found in all subcellular fractions of lymphocytes. Concentrations in nuclei mirrored changes in plasma. However, beta-carotene in mitochondria and cytosol peaked at 24 h, whereas that in microsomes peaked at 48 h. Concentrations in the latter three subcellular fractions remained high at 48 and 72 h even though plasma beta-carotene had decreased to very low concentrations. Peak concentrations of beta-carotene were highest in the nuclei, intermediate in the mitochondria and microsomes, and lowest in the cytosol. Treatment did not influence concentrations of retinol or alpha-tocopherol in the various subcellular fractions. These data provide more compelling evidence for the possible role of beta-carotene in lymphocytes.  相似文献   

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