摘要
目的探讨白藜芦醇纳米粒(resveratrol nanosuspensions,Res-NPs)对原发性免疫性血小板减少性紫癜(primary immune thrombocytopenia,ITP)大鼠调节性T细胞(regulatory T,Treg)/Th17免疫平衡的改善作用以及其对Notch1信号的调节作用。方法提取芯片数据集GSE46922和GSE23754,分析Notch1在ITP的表达。采用腹腔注射含整合素的牛血清白蛋白溶液构建ITP模型。实验大鼠随机分为正常组(Normal)、模型组(ITP)、ITP+Notch1过表达组(ITP+pc)、ITP+Res-NPs组(ITP+Res-NPs)以及ITP+Res-NPs+Notch1过表达组(ITP+Res-NPs+pc)。然后用Western blot检测脾组织中Notch1和Notch配体(Jagged1)的表达,HE染色检测病理变化,细胞计数检测各组大鼠外周血中的血小板的数目,ELISA检测血清中TNF-α、IL-6、IL-17A、TGF-β1的含量,流式细胞术检测脾单细胞悬液中Treg和Th17的百分比。结果数据集统计分析结果显示Notch1在ITP中的表达升高,Western blot结果显示Notch1过表达质粒能有效上调Notch1的表达、并能调节Jagged1的表达。白藜芦醇纳米粒能显著改善ITP模型大鼠的血小板数目,抑制血清中TNF-α、IL-6、IL-17A的释放,改善脾组织中Treg和Th17细胞的平衡,降低脾组织中Notch1和Jagged1的表达。上调Notch1则加重ITP模型鼠的上述指标恶化,联合处理组则显示上调Notch1可以部分阻断白藜芦醇纳米粒对ITP大鼠的改善效应。结论白藜芦醇纳米粒能明显升高ITP大鼠血清中血小板计数,缓解动物脾和脊髓的组织病理损伤,改善其Treg/Th17免疫平衡,这与调控Notch1信号有关。
The aim of this study is to investigate the ameliorative effect of resveratrol nanosuspensions(ResNPs)on regulatory T(Treg)/Th17 balance in primary immune thrombocytopenia(ITP)rats and its regulatory effect on Notch1 signaling pathway.Firstly,ITP chip datasets GSE46922 and GSE23754 were extracted,and the expression of Notch1 was statistically analyzed.The rats were randomly divided into normal group(Normal),model group(ITP),ITP+Notch1 overexpression group(ITP+pc),ITP+Res-NPs group(ITP+Res-NPs),ITP+Res-NPs+Notch1 overexpression group(ITP+Res-NPs+pc).The rat ITP model was established by intraperitoneal injection of integrin-bovine serum albumin.The expressions of Notch1 and Notch ligand(Jagged1)in spleen tissue were detected by Western blotting;the pathological changes were detected by HE staining;the number of platelets in peripheral blood of rats were detected by cell counting;the serum levels of TNF-α,IL-6,IL-17 A,TGF-β1 were detected by ELISA;the percentage of Treg and Th17 in spleen single cell suspension were detected by flow cytometry.Statistical analysis of the micro array dataset showed that Notch1 expression was elevated in ITP patients;and Western blot results showed that the Notch1 overexpression plasmid could effectively upregulate the expression of Notchl and regulate the expression of Jagged1.Resveratrol nanoparticles can significantly improve the number of platelets in ITP model rats,inhibit the release of TNF-α,IL-6 and IL-17 A in serum,improve the balance of Treg and Th17 cells in spleen tissue,and reduce the expression of Notchl and Jaggedl in spleen tissue.Up-regulation of Notchl aggravated the above indicators of ITP model mice,and the combined treatment group showed that up-regulation of Notchl could partially block the improvement effect of resveratrol nanoparticles on ITP rats.In conclusion,Res-NPs can significantly increase the platelet count in the serum of ITP rats,alleviate the pathological damage of the spleen and spinal cord tissues,and improve the Treg/Th17 immune balance,which is related to the regulation of Notch1 signaling.
作者
金娜
王晟
吕世琴
袁钊
郭宁红
JIN Na;WANG Sheng;LYU Shiqin;YUAN Zhao;GUO Ninghong(Clinical Trial Research Center,Second Affiliated Hospital of Nanchang University,Nanchang 330008,China;Department of Psychiatry,Jiangxi Psychiatric Hospital,Nanchang 330008,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2022年第11期990-998,共9页
Immunological Journal
基金
江西省科技厅重点研发项目(20202BBGL73031)
江西省卫生健康委员会科技计划(202310597)。
