目的探讨神经生长因子(NGF)及其高亲和力受体酪氨酸激酶A(TrkA)在支气管哮喘(BA)发病中的作用,评估其与哮喘严重程度及2型辅助T(Th2)炎症因子的相关性,并验证基于聚乳酸-羟基乙酸共聚物(PLGA)微球负载抗NGF抗体的雾化靶向治疗在重症哮...目的探讨神经生长因子(NGF)及其高亲和力受体酪氨酸激酶A(TrkA)在支气管哮喘(BA)发病中的作用,评估其与哮喘严重程度及2型辅助T(Th2)炎症因子的相关性,并验证基于聚乳酸-羟基乙酸共聚物(PLGA)微球负载抗NGF抗体的雾化靶向治疗在重症哮喘中的干预效果及机制。方法收集不同严重程度哮喘患者与非哮喘人群的血清,检测NGF、TrkA及白细胞介素4(IL-4)、IL-5、IL-13水平。构建卵清蛋白(OVA)诱导的重症哮喘小鼠模型,随机分为空白对照组、重症哮喘组、常规抗体治疗组和雾化抗NGF微球组,通过ELISA、肺功能测定、HE/Masson染色和Western blot法比较各组间支气管肺泡灌洗液(BALF)中炎症因子水平、肺组织病理变化及NGF/TrkA/核因子κB(NF-κB)蛋白表达水平差异。结果临床检测中,重度哮喘组患者较非哮喘人群对照组血清中NGF(82.52±4.01 vs 22.92±5.25)pg/mL和TrkA(53.93±8.97 vs 15.76±3.60)pg/mL水平升高;IL-4(44.23±9.88 vs 20.88±3.90)pg/mL、IL-5(147.1±14.92 vs 47.13±5.63)pg/mL、IL-13(106.9±11.64 vs 51.93±8.55)pg/mL水平显著升高。动物实验中,雾化抗NGF微球组较重症哮喘组小鼠BALF中IL-4(36.08±6.08 vs 87.35±9.13)pg/mL、IL-5(35.41±4.52 vs 81.53±4.94)pg/mL、IL-13(36.37±4.57 vs 92.37±6.53)pg/mL水平降低,第一秒用力呼气容积(FEV1)(84.68±5.33 vs 60.87±3.93)%升高、气道高反应性(AHR)(152.8±7.36 vs 233.8±8.77)%下降,肺组织病理损伤与胶原沉积减轻。Western blot法显示,雾化抗NGF微球组小鼠肺组织中NGF、TrkA和NF-κB相对蛋白水平较重症哮喘组小鼠低。结论NGF/TrkA信号通路与哮喘严重程度密切相关,雾化抗NGF微球治疗可有效靶向肺部,抑制NF-κB通路,缓解气道炎症,显著改善肺功能。展开更多
Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to ...Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.展开更多
文摘目的探讨神经生长因子(NGF)及其高亲和力受体酪氨酸激酶A(TrkA)在支气管哮喘(BA)发病中的作用,评估其与哮喘严重程度及2型辅助T(Th2)炎症因子的相关性,并验证基于聚乳酸-羟基乙酸共聚物(PLGA)微球负载抗NGF抗体的雾化靶向治疗在重症哮喘中的干预效果及机制。方法收集不同严重程度哮喘患者与非哮喘人群的血清,检测NGF、TrkA及白细胞介素4(IL-4)、IL-5、IL-13水平。构建卵清蛋白(OVA)诱导的重症哮喘小鼠模型,随机分为空白对照组、重症哮喘组、常规抗体治疗组和雾化抗NGF微球组,通过ELISA、肺功能测定、HE/Masson染色和Western blot法比较各组间支气管肺泡灌洗液(BALF)中炎症因子水平、肺组织病理变化及NGF/TrkA/核因子κB(NF-κB)蛋白表达水平差异。结果临床检测中,重度哮喘组患者较非哮喘人群对照组血清中NGF(82.52±4.01 vs 22.92±5.25)pg/mL和TrkA(53.93±8.97 vs 15.76±3.60)pg/mL水平升高;IL-4(44.23±9.88 vs 20.88±3.90)pg/mL、IL-5(147.1±14.92 vs 47.13±5.63)pg/mL、IL-13(106.9±11.64 vs 51.93±8.55)pg/mL水平显著升高。动物实验中,雾化抗NGF微球组较重症哮喘组小鼠BALF中IL-4(36.08±6.08 vs 87.35±9.13)pg/mL、IL-5(35.41±4.52 vs 81.53±4.94)pg/mL、IL-13(36.37±4.57 vs 92.37±6.53)pg/mL水平降低,第一秒用力呼气容积(FEV1)(84.68±5.33 vs 60.87±3.93)%升高、气道高反应性(AHR)(152.8±7.36 vs 233.8±8.77)%下降,肺组织病理损伤与胶原沉积减轻。Western blot法显示,雾化抗NGF微球组小鼠肺组织中NGF、TrkA和NF-κB相对蛋白水平较重症哮喘组小鼠低。结论NGF/TrkA信号通路与哮喘严重程度密切相关,雾化抗NGF微球治疗可有效靶向肺部,抑制NF-κB通路,缓解气道炎症,显著改善肺功能。
基金supported by the National Key Research and Development Program of China(2021YFD2100700)the National Natural Science Foundation of China(32021005)+1 种基金the 111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.
