摘要
本试验基于冷诱导RNA结合蛋白(CIRP)-Toll样受体4(TLR4)-肌醇需求激酶1(IRE1)信号通路,探究谷氨酰胺缓解雏鸡肺组织急性冷应激损伤的机制。选取96只1日龄圣泽901雏鸡,随机分成4组,分别为急性冷应激组(ACS组)、谷氨酰胺干预组(Gln组)、抑制剂干预组(TAK-242组)和联合干预组(Gln/TAK-242组),每组6个重复,每个重复4只。Gln组、Gln/TAK-242组自1日龄起在饮水中添加1.2%谷氨酰胺;TAK-242组、Gln/TAK-242组在6日龄时每只腹腔注射200μL的TAK-242工作液(相当于3 mg/kg BW TAK-242),Gln组、Gln/TAK-242组则注射等量生理盐水;注射完成后,对4组雏鸡进行12 h急性冷应激[(12±1)℃]处理,随后采样进行分析。结果显示:1)谷氨酰胺和TAK-242联合干预对肺组织中过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性,总抗氧化能力(T-AOC),丙二醛(MDA)含量,二胺氧化酶(DAO)、白细胞介素-6(IL-6)水平以及葡萄糖调节蛋白78(GRP78)、C反应蛋白(CRP)、DAO、IL-6、C/EBP同源蛋白(CHOP)的mRNA相对表达量存在显著或极显著的互作效应(P<0.05或P<0.01)。2)主效应分析表明,谷氨酰胺干预显著或极显著升高肺组织中CAT、超氧化物歧化酶(SOD)活性(P<0.05或P<0.01),显著或极显著降低CIRP、DAO、IL-6、肿瘤坏死因子-α(TNF-α)水平和CIRP、TLR4、IRE1、GRP78、核因子-κB(NF-κB)、CRP、DAO、IL-6的mRNA相对表达量(P<0.05或P<0.01);TAK-242干预极显著升高肺组织中SOD活性和白细胞介素-10(IL-10)水平(P<0.01),显著或极显著降低DAO、TNF-α水平和TLR4、IRE1、GRP78、NF-κB、CRP、DAO、IL-6、CHOP的mRNA相对表达量(P<0.05或P<0.01)。3)Gln/TAK-242组肺组织中SOD活性极显著高于Gln组(P<0.01),TNF-α水平及TLR4、GRP78、DAO、IL-6的mRNA相对表达量极显著低于Gln组(P<0.01);Gln/TAK-242组肺组织中T-AOC、SOD活性显著或极显著高于TAK-242组(P<0.05或P<0.01),TNF-α水平以及CIRP、TLR4、NF-κB的mRNA相对表达量显著或极显著低于TAK-242组(P<0.05或P<0.01)。上述结果提示,谷氨酰胺缓解雏鸡肺组织急性冷应激损伤的机制可能是通过CIRP-TLR4-IRE1信号通路介导NF-κB途径实现的。
This experiment investigated the mechanism by which glutamine alleviates acute cold stress-induced lung injury in chicks,focusing on the cold-inducible RNA-binding protein(CIRP)-Toll-like receptor 4(TLR4)-inositol-requiring enzyme 1(IRE1)signaling pathway.Ninety-six 1-day-old Shengze 901 chicks were randomly divided into 4 groups:the acute cold stress group(ACS group),the glutamine intervention group(Gln group),the inhibitor intervention group(TAK-242 group),and the combined intervention group(Gln/TAK-242 group).Each group consisted of 6 replicates with 4 chicks per replicate.Chicks in the Gln group and Gln/TAK-242 group were supplemented with 1.2%glutamine in drinking water from 1 day of age.Chicks in the TAK-242 group and Gln/TAK-242 group were intraperitoneally injected with 200μL/bird TAK-242 working solution(equivalent to 3 mg/kg BW of TAK-242)at 6 days of age,while those in the ACS group and Gln groups were injected with an equal volume of normal saline.Immediately after injection,all four groups were subjected to 12 h of acute cold stress at(12±1)℃,followed by sample collection and analysis.The results showed as follows:1)the combined intervention of glutamine and TAK-242 showed significant or highly significant interaction effects on the activities of catalase(CAT)and glutathione peroxidase(GSH-Px),total antioxidant capacity(T-AOC),malondialdehyde(MDA)content,the levels of diamine oxidase(DAO)and interleukin-6(IL-6),as well as the mRNA relative expression levels of glucoseregulated protein 78(GRP78),Creactive protein(CRP),DAO,IL-6,and C/EBP-homologous protein(CHOP)in lung tissue(P<0.05 or P<0.01).2)Main effect analysis revealed that glutamine intervention significantly or extremely significantly elevated the activities of CAT and superoxide dismutase(SOD)(P<0.05 or P<0.01),while it significantly or extremely significantly reduced the levels of CIRP,DAO,IL-6 and tumor necrosis factor-α(TNF-α),as well as the mRNA relative expression levels of CIRP,TLR4,IRE1,GRP78,nuclear factor-κB(NF-κB),CRP,DAO and IL-6 in lung tissue(P<0.05 or P<0.01).TAK-242 intervention extremely significantly increased the activity of SOD and the level of interleukin-10(IL-10)(P<0.01),and significantly or extremely significantly reduced the levels of DAO and TNF-α,together with the mRNA relative expression levels of TLR4,IRE1,GRP78,NF-κB,CRP,DAO,IL-6 and CHOP in lung tissue(P<0.05 or P<0.01).3)Compared with the Gln group,the Gln/TAK-242 group showed an extremely significant increase in SOD activity and IL-6 level(P<0.01),and an extremely significant decrease in TNFαlevel as well as in the mRNA relative expression levels of TLR4,GRP78,DAO and IL-6 in lung tissue(P<0.01).Relative to the TAK-242 group,the Gln/TAK-242 group exhibited a significant or extremely significant elevation in T-AOC and SOD activity(P<0.05 or P<0.01),and a significant or extremely significant reduction in TNF-αlevel and the mRNA relative expression levels of CIRP,TLR4 and NF-κB in lung tissue(P<0.05 or P<0.01).It is suggested that the mechanism of glutamine alleviating acute cold stress injury in lung tissue of chicks may be mediated by CIRP-TLR4-IRE1 signaling pathway to mediate NF-κB pathway.
作者
邱文欣
黎观红
彭优凤
曾婷瑕
邵龙毅
李艳梅
戴四发
QIU Wenxin;LI Guanhong;PENG Youfeng;ZENG Tingxia;SHAO Longyi;LI Yanmei;DAI Sifa(College of Animal Science and Technology,Jiangxi Agricultural University,Nanchang 214000,China;Department of Pharmaceutical and Life Sciences,Jiujiang University,Jiujiang 332000,China;Jiujiang Bozheng Biotechnology Industrial Research Institute,Jiujiang 332000,China)
出处
《动物营养学报》
北大核心
2026年第2期1332-1342,共11页
CHINESE JOURNAL OF ANIMAL NUTRITION
基金
江西省自然科学基金重点项目(20224ACB205010)
国家自然科学基金项目(32160799)。
