首页|骨桥蛋白通过调控LPS/TLR4信号通路在多房棘球蚴感染小鼠肝脏和脾脏免疫调节中的作用

骨桥蛋白通过调控LPS/TLR4信号通路在多房棘球蚴感染小鼠肝脏和脾脏免疫调节中的作用

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目的 探究骨桥蛋白通过调控脂多糖(LPS)/Toll样受体4(TLR4)信号通路在多房棘球蚴感染免疫调节中的作用.方法 适应性培养40只雌性Balb/c小鼠,分成4组:沉默EmOPN组、过表达EmOPN组、模型组和对照组,建立多房棘球蚴小鼠模型,沉默EmOPN组注射慢病毒LV-EmOPN-734、过表达EmOPN组注射LV-EmOPN-0423、模型组注射生理盐水,对照组不做建模处理,注射等量生理盐水.感染2周,HE法测定各组小鼠肝组织切片,检测脾脏系数和脾淋巴细胞数量,流式细胞术测定各组小鼠脾细胞凋亡情况,qRT-PCR法测定各组小鼠脾巨噬细胞极化基因表达,Western blot法测定各组小鼠肝组织LPS和TLR4信号通路蛋白表达情况.结果 过表达EmOPN组脾脏系数和脾淋巴细胞数量明显高于其他3组(P<0.05).过表达EmOPN组、模型组和沉默EmOPN组等感染亚组小鼠肝脏组织呈现多个不规则大小的白色病灶,这些病灶与周围正常肝组织之间没有明显的分界线,且在内部呈现浸润性生长的特征.此外,4组小鼠的脾细胞凋亡率差异有统计学意义(F=66.874,P<0.001);4组小鼠巨噬细胞IL-1β(F=279.123,P<0.001)、IFN-γ(F=139.997,P<0.001)、CCR7(F=23.120,P<0.001)、MRC1(F=35.386,P<0.001)和Retnla(F=153.844,P<0.001)的mRNA差异有统计学意义;4组小鼠的LPS蛋白(F=179.625,P<0.001)和TLR4蛋白表达(F=215.71,P<0.001)差异有统计学意义.结论 多房棘球蚴病肝脏和脾脏功能出现异常,骨桥蛋白可升高LPS/TLR4信号通路纠正巨噬细胞免疫功能紊乱.
Roles of osteopontin in the immune regulation of multilocular echinococcosis infection by regulating LPS/TLR4 signaling pathway
The purpose of this study is to investigate the role of osteopontin in modulating the LPS/TLR4 signaling pathway during the immune response to multilocular echinococcosis infection.A total of forty female Balb/c mice were recruited and divided into four distinct groups:EmOPN silencing group,EmOPN overexpressing group,model group,and control group.Multilocular echinococcosis model was established in mice,and the mice were treated accordingly.The EmOPN silencing group received lentivirus LV-EmOPN-734,the EmOPN overexpressing group received lentivirus LV-EmOPN-0423,the model group was injected with normal saline,while the control group did not receive any modeling treatment and was also injected with normal saline.After two weeks of infection,various parameters were measured,including liver tissue sections,spleen coefficients,and splenic lymphocyte counts.Additionally,apoptosis in splenic cells was analyzed using flow cytometry,and the expression levels of LPS and TLR4 signaling pathway proteins in liver tissues were assessed by qRT-PCR and Western blot techniques.Data showed that there are significant variations among the four groups in terms of spleen index,splenic lymphocyte count,and apoptotic rates.Notably,the EmOPN overexpressing group exhibited significantly higher spleen index and lymphocyte count compared to the other groups.Liver tissues from infection mice of the three groups displayed irregular white lesions with infiltrative growth,whereas the liver tissue of the control group appeared normal.Moreover,the EmOPN overexpressing group displayed remarkable differences in the mRNA levels of cytokines like IL-1β and IFN-γ,as well as immune response-related genes such as CCR7,MRC1,and Retnla.Additionally,significant differences in protein expression levels of LPS and TLR4 were observed in the four groups.Taken together,in alveolar echinococcosis,liver and spleen functions are impaired.And osteopontin has the potential to enhance the LPS/TLR4 signaling pathway,thereby correcting macrophage immune dysfunction.

OsteopontinLipopolysaccharideToll-like receptor 4Alveolar echinococcosisImmune function

黄丹、樊晶

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430023,华中科技大学同济医学院附属武汉市金银潭医院消化科

骨桥蛋白 脂多糖 Toll样受体4 多房棘球蚴 免疫功能

2024

免疫学杂志
第三军医大学,中国免疫学会

免疫学杂志

CSTPCD
影响因子:0.704
ISSN:1000-8861
年,卷(期):2024.40(4)