牛磺酸通过维持线粒体功能稳态缓解呕吐毒素对断奶仔猪回肠的损伤作用OA
Taurine Alleviates Deoxynivalenol-Induced Ileal Injury in Weaned Piglets by Maintaining Mitochondrial Functional Homeostasis
本试验旨在探究牛磺酸(TAU)对呕吐毒素(DON)诱导断奶仔猪回肠损伤的缓解作用及其潜在机制.选取 18 头体重相近的 21 日龄健康断奶仔猪,随机分为 BD 组(饲喂基础饲粮)、DON组(饲喂 3 mg/kg DON污染饲粮)和DON+TAU组(饲喂 3 mg/kg DON污染饲粮+3 000 mg/kg TAU),每组 6 个重复,每个重复 1 头猪.试验期 24 d.结果表明:1)与BD组相比,DON暴露显著降低回肠绒毛高度和绒毛高度/隐窝深度值(P<0.05),显著提高隐窝深度(P<0.05),显著减少杯状细胞数量(P<0.05),显著降低黏蛋白 2(MUC2)mRNA相对表达量和相对荧光强度以及紧密连接蛋白[闭锁小带蛋白 2(ZO2)、闭合蛋白(OCLN)和密封蛋白 1(CLDN1)]mRNA和蛋白相对表达量(P<0.05);显著提高 8-羟基脱氧鸟苷(8-OHdG)和丙二醛(MDA)含量(P<0.05),显著降低总超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性及谷胱甘肽(GSH)含量(P<0.05),显著降低抗氧化相关基因核因子 E2 相关因子 2(Nrf2)、血红素加氧酶 1(HO1)、超氧化物歧化酶 1(SOD1)和超氧化物歧化酶 2(SOD2)mRNA相对表达量(P<0.05);显著提高炎症因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)]含量和细胞凋亡率(P<0.05),显著下调抗凋亡基因 B 细胞淋巴瘤 2(BCL2)表达并显著上调促凋亡基因B细胞淋巴瘤 2 相关X蛋白(BAX)、细胞色素C(CYCS)、半胱天冬酶 9(CASP9)、半胱天冬酶 3(CASP3)和线粒体相关诱导凋亡因子 1(AIFM1)表达(P<0.05),显著提高BAX、裂解(cleaved)CASP3 和AIFM1 蛋白相对表达量(P<0.05);造成线粒体结构破坏,显著降低线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅳ活性以及ATP含量和线粒体DNA(mtDNA)相对拷贝数(P<0.05),引起线粒体质量控制失衡[过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC1α)、核呼吸因子 1(NRF1)、线粒体转录因子A(TFAM)、线粒体融合蛋白 2(MFN2)表达显著下调(P<0.05),动力蛋白相关蛋白 1(DRP1)、线粒体裂变蛋白 1(FIS1)、PTEN诱导激酶1(PINK1)、帕金蛋白RBR E3 泛素蛋白连接酶(PRKN)、微管相关蛋白1 轻链3β(LC3B)表达显著上调(P<0.05)].2)与DON组相比,TAU处理显著改善回肠组织形态结构受损和屏障功能相关指标下调(P<0.05);显著降低MDA含量(P<0.05),显著提高T-SOD活性(P<0.05),显著上调抗氧化相关基因表达(P<0.05);显著降低IL-1β和IL-8 含量及细胞凋亡率(P<0.05),并显著逆转凋亡基因和蛋白的异常表达(P<0.05);改善线粒体结构,显著提高线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅲ和Ⅳ活性以及ATP含量和mtDNA相对拷贝数(P<0.05);显著改善线粒体质量控制过程(P<0.05),维持其功能稳态.综上所述,饲粮中添加TAU可通过调控线粒体质量控制维持其功能稳态,减轻氧化应激、炎症反应和细胞凋亡,并改善屏障功能,最终缓解DON对断奶仔猪回肠造成的损伤.
This study aimed to investigate the alleviating effects of taurine(TAU)on deoxynivalenol(DON)-induced ileal injury in weaned piglets and to elucidate its potential underlying mechanisms.A total of 18 healthy weaned piglets at 21 days of age with similar body weight were randomly assigned into three groups as BD group(fed basal diet),DON group(fed 3 mg/kg DON-contaminated diet),and DON+TAU group(fed 3 mg/kg DON-contaminated diet+3 000 mg/kg TAU)with 6 replicates in each group and 1 pig in each repli-cate,and fed for 24 days.The results showed as follows:1)compared with BD group,DON exposure signifi-cantly decreased the ileal villus height and villus height to crypt depth ratio(P<0.05),significantly increased the crypt depth(P<0.05),significantly decreased the goblet cell number(P<0.05),and significantly reduced the mucin 2(MUC2)mRNA relative expression level and relative fluorescence intensity,as well as downregu-lating both the mRNA and protein relative expression levels of tight junction proteins[zonula occludens 2(ZO2),occludin(OCLN)and claudin 1(CLDN1)](P<0.05).DON significantly elevated the 8-hydroxydeoxyguanosine(8-OHdG)and malonaldehyde(MDA)contents,while significantly reduced the ac-tivities of total superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px)as well as glutathione(GSH)content,and significantly decreased the mRNA relative expression levels of antioxidant-related genes such as nuclear factor E2-related factor 2(Nrf2),heme oxygenase 1(HO1),superoxide dismutase 1(SOD1)and superoxide dismutase 2(SOD2)(P<0.05).Moreover,DON significantly increased the contents of pro-inflammatory cytokines[interleukin-1β(IL-1β),interleukin-6(IL-6)and interleukin-8(IL-8)]and cell apoptosis rate(P<0.05),significantly suppressed B-cell lymphoma 2(BCL2)expression and upregulated B-cell lymphoma 2-associated X protein(BAX),cytochrome C(CYCS),Caspase 9(CASP9),Caspase 3(CASP3)and apoptosis inducing factor mitochondria associated 1(AIFM1)expression(P<0.05),and sig-nificantly increased the protein relative expression levels of BAX,cleaved CASP3 and AIFM1(P<0.05).In addition,DON disrupted mitochondrial structure,significantly reduced the activities of mitochondrial respirato-ry chain complexes Ⅰ,Ⅱ and Ⅳ,as well as ATP content and mitochondrial DNA(mtDNA)relative copy number(P<0.05),and induced the mitochondrial quality control imbalance[significant downregulation of ex-pression of peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α),nuclear respiratory factor 1(NRF1),transcription factor A,mitochondrial(TFAM),and mitofusin 2(MFN2)(P<0.05),and signifi-cant upregulation of expression of dynamin-related protein 1(DRP1),fission,mitochondrial 1(FIS1),PTEN induced kinase 1(PINK1),Parkin RBR E3 ubiquitin protein ligase(PRKN)and microtubule associat-ed protein 1 light chain 3β(LC3B)(P<0.05)].2)Compared with DON group,TAU treatment significantly alleviated the injury of morphological structure of ileal tissues and the down-regulation of barrier function-relat-ed indices(P<0.05),significantly reduced the MDA content(P<0.05),significantly increased the T-SOD activity(P<0.05),and significantly upregulated antioxidant-related gene expression(P<0.05).TAU also sig-nificantly reduced the contents of IL-1β and IL-8 as well as cell apoptosis rate(P<0.05),significantly re-versed the abnormal expression of apoptosis-related genes and proteins(P<0.05),restored mitochondrial structure,significantly enhanced the activities of mitochondrial respiratory chain complexesⅠ,Ⅱ,ⅢandⅣ,as well as ATP content and mtDNA relative copy number(P<0.05),and significantly improved the mitochon-drial quality control process(P<0.05)and maintained its functional homeostasis.In conclusion,dietary sup-plementation of TAU can alleviate DON-induced ileal injury in weaned piglets,potentially by regulating mito-chondrial quality control to maintain mitochondrial functional homeostasis,reducing oxidative stress,inflamma-tion and apoptosis,as well as improving barrier function.[Chinese Journal of Animal Nutrition,2026,38(3):2138-2153]
计徐;丁红研;周芬;张峰;吴东
安徽省农业科学院畜牧兽医研究所,安徽省畜禽产品安全重点实验室,合肥 230001安徽省农业科学院畜牧兽医研究所,安徽省畜禽产品安全重点实验室,合肥 230001安徽省农业科学院畜牧兽医研究所,安徽省畜禽产品安全重点实验室,合肥 230001安徽科技学院动物科学学院,安徽省动物营养调控与健康重点实验室,凤阳 233100安徽省农业科学院畜牧兽医研究所,安徽省畜禽产品安全重点实验室,合肥 230001
农业科技
牛磺酸呕吐毒素断奶仔猪回肠损伤线粒体功能稳态
taurinedeoxynivalenolweaned pigletsileal injurymitochondrial functional homeostasis
《动物营养学报》 2026 (3)
2138-2153,16
国家自然科学基金项目(32202728)安徽省重点研究和开发计划项目(201904a06020012)安徽省农业科学院青年英才计划(QNYC-202205)
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