共查询到18条相似文献,搜索用时 78 毫秒
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目的评价百合乌药蒲公英汤(DecotionofBaiheWuyaoPugongying,DBWP)对I型糖尿病(type1diabetes,T1D)肝病的改善作用,并进行机制探讨。方法8周龄雄性昆明小鼠腹腔注射链脲佐菌素(streptozotocin,STZ)制备T1D模型,模型制备成功后随机将小鼠分为7组,随后用不同剂量DBWP连续灌胃6周进行效果评价。然后观察小鼠肝组织形态学变化和纤维化状况;检测肝功能、空腹血糖和血清胰岛素水平;检测血清中抗氧化因子含量;同时检测肝脏炎症因子、抗氧化因子和糖异生因子在mRNA水平的表达。结果DBWP给药后,与模型组相比,给药组小鼠体重有所上升,血糖值降低,血清胰岛素水平升高,以中剂量组效果最为明显;染色结果可见肝细胞排列整齐紧密,肝脏病理损伤有所恢复;血清生化相关酶含量明显降低,且以低1剂量最为明显;给药组抗氧化因子超氧化物歧化酶(superoxidedismutase,SOD)中、低1剂量组明显上升、丙二醛(malondialdehyde,MDA)含量以中、高剂量下降明显,自由基清除能力增强,整体药效以中剂量效果最为显著。通过对DBWP组中剂量组进行检测,结果发现,与模型组相比,给药组肝脏中炎症相关因子在mRNA水平表达减少,抗炎抗氧化水平增强,DBWP可降低肝脏中糖原合成因子的表达,糖异生抑制明显。结论DBWP通过减轻炎症、增加抗氧化能力来改善血糖,减轻T1D及其并发肝损伤。 相似文献
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目的:观察桑叶生物碱对转化生长因子-β1(transforming growth factor-β1,TGF-β1)/Smads信号通路及基质金属蛋白酶-13(matrix metalloproteinase-13,MMP-13)、基质金属蛋白酶抑制剂-1(inhibitor of metalloproteinase-1,TIMP-1)mRNA表达的调节作用,探讨桑叶生物碱改善小鼠肝纤维化的作用机制。方法:采用腹腔注射体积分数10% CCl4 橄榄油溶液(5 mL/kg mb)联合高脂饮食诱导小鼠肝纤维化模型。造模8 周后,正常对照组和模型组给予蒸馏水,低、中、高剂量组分别灌胃50、100、200 mg/kg mb剂量的桑叶生物碱,阳性药物组给予100 mg/kg mb水飞蓟宾,持续45 d。采用酶联免疫试剂盒测定各组小鼠肝组织α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、I型胶原蛋白(collagen I,Col I)及III型胶原蛋白(collagen III,Col III)含量;采用实时定量聚合酶链式反应测定肝组织TGF-β1、Smad3、Smad4、Smad7、MMP-13、TIMP-1 mRNA表达水平。结果:与模型组比,灌胃高剂量桑叶生物碱(200 mg/kg mb)的小鼠肝组织中α-SMA、Col I、Col III含量分别降低19.55%、19.93%、13.84%(P<0.05);TGF-β1、Smad3、Smad4、TIMP-1 mRNA表达水平分别下降59.04%、56.73%、50.70%、49.09%(P<0.05),Smad7、MMP-13 mRNA表达水平分别上升48.29%、25.72%(P<0.05)。结论:桑叶生物碱能改善小鼠肝纤维化,其机制可能是对TGF-β1/Smads信号通路相关因子和TIMP-1、MMP-13的基因表达具有调控作用。 相似文献
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研究小金海棠多酚对CCl4诱导小鼠肝纤维化的改善作用及机制。采用皮下注射CCl4诱导小鼠肝纤维化,同时小金海棠多酚(MXP)灌胃给药(10 mg/kg、20 mg/kg)的方法。结果表明,皮下注射CCl4诱导小鼠肝脏发生明显的损伤。与模型组相比,喂食小金海棠多酚显著降低了血清和肝组织中ALT与AST活性,同时肝组织中SOD和GSH-PX活性显著提高。形态和组织学检测表明,小金海棠多酚显著逆转CCl4诱导的肝损伤。此外,喂食小金海棠多酚能显著抑制皮下注射CCl4引发的IL-1、IL-6和TNF-α等炎性细胞因子的生成。以上结果表明,小金海棠多酚可以明显减轻CCl4诱导产生的肝纤维化,其作用机制可能与其增强机体抗氧化能力、抑制炎性细胞因子合成有关。 相似文献
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研究辣木叶(Moringa oleifera Lam,LM)水提物对大鼠肝纤维化(Hepatic Fibrosis,HF)的改善作用和机制。60只雄性SD大鼠随机分为空白组、模型组、秋水仙碱组(100 mg/kg),以及LM高、中、低剂量组(200、100、50 mg/kg),除空白组外,其余组大鼠通过腹腔注射硫代乙酰胺(Thiacetamide,TAA)建立HF模型,自第5周开始灌胃给药。给药结束后检测大鼠体重、肝脏指数、血清丙氨酸氨基转移酶(Alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(Aspartate aminotransferase,AST)、HF指标(血清Ⅲ型前胶原(procollagenⅢ, PCⅢ)、 IV型胶原(IVcollagenIV-C)、层黏蛋白(laminin, LN)、透明质酸(hyaluronidase,HA)、肝脏羟脯胺酸(HYP)、Masson染色观察肝脏纤维组织病变、氧化应激指标(肝脏活性氧(reactiveoxygen, ROS)、丙二醛(malondialdehyde, MDA)、超氧化物歧化酶(superox... 相似文献
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为探究百合花醇提物花青素对CCl_4所致的大鼠肝纤维化的预防、改善作用及可能机制。将32只大鼠随机分为对照组(Sham)、肝纤维化模型组(M)、百合花花青素低剂量组(LFF 0.5 g/mL)和高剂量组(LFF 1.0 g/mL)。M组、LFF组大鼠背部皮下注射50%CCl_4造模,每周2次,连续8周。LFF组大鼠给予不同剂量的百合花花青素提取物灌胃,Sham组和M组给予等体积的生理盐水,每天1次。8周后处理动物,采集血清检测ALT、AST;肝组织匀浆测定SOD、CAT、GSH-Px活力和MDA含量;Western-blot测定肝组织TGF-β1和α-SMA的表达。实验结果表明,与模型M组比较,百合花花青素能明显降低大鼠血清中ALT、AST水平;使肝组织抗氧化酶活力SOD、CAT、GSH-Px显著上升,脂质过氧化物MDA生成减少,进而诱导肝组织纤维化相关物质TGF-β1、α-SMA表达下调。百合花花青素具有良好的抗氧化活性,改善大鼠肝损伤,并逆转CCl_4诱导的肝纤维化,其机制可能与抗脂质过氧化物损伤及下调细胞外纤维组织增生有关。 相似文献
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目的:探讨膳食核苷酸对SAMP8小鼠肝脏纤维化的改善作用。方法:采用SPF级SAMP8小鼠48只,按体重随机分为正常对照组、核苷酸低剂量组、核苷酸中剂量组、核苷酸高剂量组,另取12只SAMR1小鼠作为模型对照组。正常对照组、模型对照组均采用基础饲料进行喂养,核苷酸低、中、高剂量组采用额外添加0.3、0.6、1.2 g/kg核苷酸的基础饲料进行喂养。所有组自3月龄开始干预,干预时长9个月。小鼠12月龄时,对小鼠肝组织进行HE染色观察肝脏组织病理学结构,检测肝脏羟脯氨酸、纤维化相关因子和氧化应激指标,同时选取正常对照组和核苷酸低剂量组进行转录组测序,对差异基因进行KEGG富集。结果:与模型对照组相比,正常对照组肝脏组织肝索结构紊乱,肝细胞排列不整齐,炎症细胞浸润。与正常对照组相比,膳食核苷酸显著改善了增龄性肝脏纤维化程度,提高肝脏SOD、GSH-Px活力,降低肝脏脂质过氧化物MDA水平。核苷酸还显著影响了细胞周期、氨基酸的生物合成和糖酵解/糖异生通路。结论:膳食核苷酸对SAMP8小鼠肝脏具有抗纤维化作用。 相似文献
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本文研究了蒲公英提取物对类风湿性关节炎模型大鼠的作用机制。通过建立类风湿性关节炎模型,对大鼠进行病理学观察,并对治疗效果的相关指标如检测白介素-17(Interleukin-17,IL-17)、白介素-23(Interleukin-23,IL-23)、白介素-1(Interleukin-1,IL-1)、hs CRP、白介素-1β(Interleukin-1β,IL-1β)IL-1β、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、护骨素(Osteoprotegerin,OPG)、核因子KB配体受体激活因子(RANKL、RANK)水平进行检测。研究结果表明:高剂量蒲公英组大鼠足跖肿胀度(6.42±1.06)低于模型组大鼠足跖肿胀度(15.18±2.65)(p0.05),扭体(9.0±2.0)、缩足次数(8.5±1.5)高于模型组扭体(2.2±0.4)、缩足次数(2.4±0.5)。高剂量蒲公英组大鼠的IL-17、IL-23、IL-1、hs CRP、IL-1β、TNF-α等水平均低于模型组大鼠(p0.01)。高剂量蒲公英组大鼠的OPG(0.42±0.06)、RANKL(0.52±0.08)、RANK蛋白表达(0.45±0.05)显著低于模型组OPG(1.18±0.15)、RANKL(1.35±0.46)、RANK蛋白表达(1.23±0.45)(p0.01)。研究结果说明蒲公英提取物通过调控OPG/RANKL/RANK信号通路,抑制炎症因子水平表达,能显著改善风湿性关节炎模型大鼠的治疗效果。 相似文献
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目的:考察百合乌药汤(Baihe Wuyao decoction,BWD)对小鼠1型糖尿病(Type 1 diabetes mellitus,T1DM)并发肝损伤的保护作用,并揭示其潜在机制。方法:小鼠70只,随机选取10只作为空白组,其余采用腹腔注射链脲佐菌素(Streptozotocin,STZ)诱导T1DM,成模后随机分为6组:模型组、阳性对照组、BWD各剂量组(15、5、2.5、1.25 g·kg?1·d?1)。各组小鼠连续给药6周。检测小鼠血清中谷丙转氨酶(Alanine aminotransferase,ALT)、谷草转氨酶(Aspartate aminotransferase,AST)的含量,及肝组织匀浆超氧化物歧化酶(Superoxidedismutase,SOD)和丙二醛(Malonaldehyde,MDA)的含量;观察小鼠肝脏病理学变化;检测小鼠肝脏中蛋白激酶B(Protein kinase B,AKT)在蛋白水平的表达,检测锰超氧化物歧化酶(Manganese superoxide dismutase,Mn-SOD)和一氧化氮合酶(Inducible nitric oxide synthase,iNOS)、炎症因子包括肿瘤坏死因子(Tumor necrosis factor,TNF-α)、核因子-κB(Nuclear factor-κB,NF-κB)、白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)和白细胞介素-8(Interleukin-8,IL-8)、凋亡因子包括(B-cell lymphoma-2,Bcl2)、(Bcl2-associated X protein,Bax)和(Caspase 3,CASP3)在mRNA水平的表达。结果:BWD可改善T1DM小鼠肝组织病理损伤;与模型组相比,各剂量组ALT和AST水平均显著降低(P<0.01或P<0.05),低1剂量组效果更明显;BWD低1剂量可显著上调p-AKT/AKT(P<0.05);低1剂量显著下调MDA、iNOS,上调SOD、Mn-SOD含量(P<0.01或P<0.05);与模型组相比,低1剂量的Bcl2/Bax比值明显增加,Bax、CASP3被下调;低1剂量显著降低TNF-α、NF-κB、IL-1β、IL-6和IL-8在基因水平的表达(P<0.01或P<0.05)。结论:BWD可通过抗炎、抗氧化、抗凋亡、促进细胞增殖以及改善胰岛素信号通路发挥对T1DM并发肝损伤的保护作用。 相似文献
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《Journal of dairy science》2023,106(4):2700-2715
Fatty liver (i.e., hepatic lipidosis) is a prevalent metabolic disorder in dairy cows during the transition period, characterized by excess hepatic accumulation of triglyceride (TG), tissue dysfunction, and cell death. Detailed pathological changes, particularly hepatic fibrosis, during fatty liver remain to be determined. Liver fibrosis occurs as a consequence of liver damage, resulting from the excessive accumulation of extracellular matrix, which distorts the architecture of the normal liver, compromising its normal synthetic and metabolic functions. Thus, we aimed to investigate liver fibrosis status and its potential causal factors including oxidative stress, hepatocyte apoptosis, and production of inflammatory cytokines in the liver of cows with fatty liver. Forty-five dairy cows (parity, 3–5) were selected, and liver biopsy and blood were collected on the second week postpartum (days in milk, 10–14 d). On the basis of the degree of lipid accumulation in liver, selected cows were categorized into normal (n = 25; TG <1% wet wt), mild fatty liver (n = 15; 1% ≤ TG <5% wet wt), and moderate fatty liver (n = 5; 5% ≤ TG <10% wet wt). Compared with normal cows, blood concentrations of nonesterified fatty acids and β-hydroxybutyrate, along with alanine aminotransferase and aspartate aminotransferase activities, were greater in the cows with fatty liver (mild and moderate). Hepatic extracellular matrix deposition, as indicated by Picrosirius red staining, was greater in cows with fatty liver than those with normal ones. In addition, we observed an increased proportion of collagen type I fiber in extracellular matrix with increased lipid accumulation in the liver. Compared with normal cows, the area of α-smooth muscle actin (α-SMA)-positive staining along with the mRNA abundance of collagen type I α 1 (COL1A1), ACTA2 (gene encoding α-SMA), and transforming growth factor-β (TGFB) were greater in cows with fatty liver. Compared with normal cows, hepatic contents of malondialdehyde, glutathione disulfide, and 8-isoprostane were greater, whereas total antioxidant capacity, the hepatic content of glutathione, and activities of antioxidant indicators, including superoxide dismutase, glutathione peroxidase, and catalase, were lower in cows with fatty liver. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells and abundance of apoptosis-related molecules BAX, CASP3, CASP8, and CASP9 were greater in cows with fatty liver. However, mRNA abundance of the anti-apoptotic gene BCL2 did not differ. The mRNA abundance of pro-inflammatory cytokines including tumor necrosis factor-α (TNFA), interleukin-1β (IL1B), and interleukin-6 (IL6) was greater in the liver of cows with fatty liver. Overall, the present study indicated that fibrosis is a common pathological response to liver damage and is associated with oxidative stress, hepatocyte death, and inflammation. 相似文献
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Yin‐Ching Chan Shih‐Chieh Chang Sin‐Yie Liu Hsin‐Ling Yang You‐Cheng Hseu Jiunn‐Wang Liao 《Journal of the science of food and agriculture》2010,90(1):161-167
BACKGROUND: In a previous study, lyophilised yam reduced brain amyloid β‐protein (Aβ) accumulation and improved the antioxidative defence system in senescence‐accelerated (SAMP8) mice. Therefore, the aim of this study was to investigate the hepatic protection of yam in the carbon tetrachloride‐induced hepatic fibrosis of rats. Hepatic fibrosis was induced in rats via intraperitoneal injections of CCl4 at a dose of 1 mL kg?1 body weight (BW) twice weekly for 8 weeks. Three groups of rats were gavaged daily with yams at doses of 0.5, 1 and 2 g kg?1 BW for 8 weeks, respectively. RESULTS: Yam treatments significantly decreased the ratio of liver/body weight, levels of γ‐glutaminotranspeptidase (GGT), low‐density lipoprotein, and triglyceride in serum when compared with those administered CCl4 alone. Treatment with yams significantly elevated antioxidant activities of glutathione peroxidase (GSH‐Px) and superoxidase dismutase (SOD) in livers. Microscopically, yam‐treated groups presented with low histoscores of CCl4‐induced liver injury and fibrosis. Additionally, yam treatment reduced the area of GGT‐positive foci and the index of proliferating cell nuclear antigen (PCNA) in liver. CONCLUSION: Daily administration of yam attenuates CCl4‐induced hepatic fibrosis in rats in a dose‐dependent manner; this attenuation may be related to the antioxidant properties of yams. Copyright © 2009 Society of Chemical Industry 相似文献
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Chen IS Chen YC Chou CH Chuang RF Sheen LY Chiu CH 《Journal of the science of food and agriculture》2012,92(7):1441-1447
BACKGROUND: Liver fibrosis is chronic liver damage usually caused by alcohol, viruses or other toxins and is characterised by an excessive accumulation of extracellular matrix proteins such as collagen. The aim of this study was to establish an animal model of chronic liver damage and investigate molecular mechanisms of silymarin hepatoprotective effects. RESULTS: Thioacetamide (TAA; 100 mg kg?1 intraperitoneal (i.p.) injection three times weekly) effectively induced chronic liver fibrosis in male ICR mice. Then 24 ICR mice were randomly divided into four groups: (1) saline (i.p.) + water (gavage); (2) saline (i.p.) + 150 mg kg?1 silymarin (gavage); (3) 100 mg kg?1 TAA (i.p.) + water (gavage); (4) 100 mg kg?1 TAA (i.p.) + 150 mg kg?1 silymarin (gavage). Eight weeks of TAA treatment resulted in lower body weight, serum cholesterol and triglycerides as well as increased liver size, ALT, AST and LDH values (P < 0.05). These TAA‐induced effects were attenuated by silymarin (P < 0.05); therefore silymarin also ameliorated TAA‐induced liver lesions. Effects of silymarin on TAA‐induced chronic liver damage may be attributed to down‐regulation of hepatic MMP‐2, MMP‐13, TIMP‐1, TIMP‐2, AP‐1, KLF6, TGF‐β1, α‐SMA and COL‐α1. CONCLUSION: A mouse model of chronic liver fibrosis was successfully established by injecting 100 mg kg?1 TAA three times weekly in male ICR mice. Meanwhile, silymarin showed hepatoprotection against TAA‐induced damage. Copyright © 2011 Society of Chemical Industry 相似文献
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研究余甘子提取物(extractum phyllanthus emblica,EPE)对小鼠急性酒精肝损伤的预防保护作用和机制。方法:60只雄性小鼠随机分为空白组、模型组、药物对照组(美他多辛胶囊-欣立得,200 mg/kg·d)和EPE高、中、低剂量组(400、160、80 mg/kg·d),灌胃给药30 d,末次给药后1 h灌胃56%乙醇造急性酒精肝损伤模型。12 h后检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、白介素10(IL-10)浓度,检测肝脏丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、乙醇脱氢酶(ADH)含量,实时荧光定量PCR(real time PCR)检测肝脏脂肪酸合成酶(FAS)、脂肪分化相关蛋白(ADRP)、细胞色素P450 2E1(CYP2E1)、过氧化酶体增殖激活α受体(PPARα)和半胱氨酸天冬氨酸蛋白酶3(Caspase3)mRNA的表达,HE染色观察肝脏组织病理变化。结果表明:EPE能显著降低小鼠血清ALT、AST、TG浓度,减轻肝脏病理损伤;EPE显著提高肝脏乙醇代谢酶ADH、CAT活性,下调CYP2E1 mRNA表达水平,缩短小鼠醒酒时间;EPE显著下调脂肪酸合成酶FAS和转运酶ADRP基因表达,抑制脂肪酸合成和向肝脏转运;EPE显著提高肝脏抗氧化酶SOD、GSH-Px活性,降低MDA浓度,发挥抗氧化活性保护肝脏损伤;EPE显著降低炎性因子TNF-α和IL-6浓度,减轻肝脏炎症损伤,但对IL-10浓度没有显著影响;EPE显著下调Casepase3基因表达,降低肝脏细胞凋亡水平;EPE显著上调PPARα基因表达来减轻肝脏氧化和炎症损伤。结论:EPE通过乙醇代谢酶活性调节、脂代谢调控、抗氧化损伤、抗炎和抗细胞凋亡来保护小鼠急性酒精肝损伤,具有开发为解酒护肝保健食品的前景。 相似文献
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F. Pietsch M. Schären T. Snedec K.B. Theinert A.-S. Leonhardt A. Kaiser F. Rachidi D. Böttcher J. Scheinert H.-A. Schoon P. Wohlsein J. Spilke A. Haudum W. Baumgartner A. Starke 《Journal of dairy science》2021,104(8):9227-9244
The aims of this study were to evaluate histopathologic changes during the transition period, describe the histopathological features of the metabotypes identified in Part I (Schären et al., 2021b), and investigate effects of a metaphylactic treatment with butaphosphan and cyanocobalamin (BCC) on the liver parenchyma. Eighty German Holstein cows (mean 305-d production: 10,957 kg, range: 6,480–15,193 kg; mean lactation number: 3.9, range: 2–9) from a commercial dairy farm in Saxony, Germany, were enrolled in a randomized, prospective, triple-blinded study. Two groups received a treatment with BCC (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin, Catosal, Bayer Animal Health, n = 20 each) and one group a placebo treatment (NaCl 0.9%, n = 40). Liver biopsy specimens were collected 14 d antepartum (AP) and 7, 28, and 42 d postpartum (PP), routinely processed for histologic examination, and stained with hematoxylin and eosin, Sudan III, periodic acid-Schiff, and picrosirius red stains. The sections were assessed for fat and glycogen content and degenerative, inflammatory, fibrotic, and proliferative changes. The statistical analysis included the effects of the sampling day, the lactation number, the treatment, and the metabotype (A = medium, B = minor, C = large alterations in the liver metabolome profile between AP and PP status). There was mild to moderate fat infiltration in the liver of 37% of cows in the last 2 wk AP, and moderate to severe fat infiltration in 66% of cows in the first days PP. The degree of fat infiltration increased from 2 wk AP until the end of the first week PP, and then decreased until the end of the study period, at which time about 25% of cows had moderate to severe fatty infiltration. Lipidosis was positively correlated with the severity of liver cell degeneration, and negatively correlated with the degree of glycogen deposits. Complete glycogen depletion of hepatocytes was not observed in cows, even in the presence of severe hepatic lipidosis. Moderate to severe lymphocytic hepatitis was seen in 39% of cows throughout the study period, and cows with lactation numbers 5 or greater had perisinusoidal fibrosis more often than younger cows. Severe fibrosis and cirrhosis of the liver did not occur. Metabotype B animals exhibited a higher chance of fatty infiltration, lower glycogen storage, and perisinusoidal fibrosis and for this metabotype positive correlations were calculated between increased fat deposition in the liver and marked glycogen depletion, and increased degenerative, inflammatory, fibrotic, and proliferative changes of hepatic tissue. For the treatment with BCC, no significant effect was observed. In summary, during the transition period, the liver of dairy cows is characterized by fat accumulation and glycogen depletion and histologic signs of hepatitis and hepatocyte degeneration. These histomorphologic changes were accentuated in animals exhibiting little alterations in their liver metabolome profile across the transition period (metabotype B) and support the assumption of a decreased grass silage quality as a causative factor. 相似文献