| 王海晨,黎 明,王馨笛,张永健,钟 亮.过表达IDO骨髓间充质干细胞对腹腔异位移植心脏模型大鼠炎症反应、T细胞亚群和NF-κB/NLRP3通路的影响[J].现代生物医学进展英文版,2023,(7):1212-1217. |
| 过表达IDO骨髓间充质干细胞对腹腔异位移植心脏模型大鼠炎症反应、T细胞亚群和NF-κB/NLRP3通路的影响 |
| Effects of IDO Overexpression of Bone Marrow Mesenchymal Stem Cells on Inflammatory Response, T Cell Subsets and NF-κB/NLRP3 Pathway in Abdominal Ectopic Heart Transplantation Model Rats |
| Received:December 03, 2022 Revised:December 26, 2022 |
| DOI：10.13241/j.cnki.pmb.2023.07.003 |
| 中文关键词: 吲哚胺2，3-双加氧酶 骨髓间充质干细胞 炎症反应 T细胞亚群 NF-κB/NLRP3信号通路 |
| 英文关键词: Indoleamine 2, 3-dioxygenase Bone marrow mesenchymal stem cells Inflammatory response T cell subsets NF-κB/NLRP3 signaling pathway |
| 基金项目:陕西省重点研发计划项目（2022SF-170） |
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| 中文摘要: |
| 摘要 目的：探讨过表达吲哚胺2，3-双加氧酶（IDO）骨髓间充质干细胞（BMSCs）对腹腔异位移植心脏模型大鼠炎症反应、T细胞亚群和核因子（NF）-κB/核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）通路的影响。方法：慢病毒载体及基因开启技术构建过表达IDO大鼠BMSCs，建立60只大鼠腹腔异位移植心脏模型，造模成功后，随机分为4组，每组各15只。空白组建模后未给予任何处理，吗替麦考组喂养吗替麦考40 mg/kg，空白-BMSCs组在腹腔异位移植心脏术后3 d，经尾静脉注射空白-BMSCs，IDO组在腹腔异位移植心脏术后3 d，经尾静脉注射过表达IDO-BMSCs（每只400 μL，106个细胞）。检测并对比四组心功能、血清心肌酶、炎症因子、T细胞亚群、心脏病理变化以及NF-κB/NLRP3通路相关蛋白表达情况。结果：IDO组射血分数差值、环比收缩（FS）差值大于空白组、吗替麦考组、空白-BMSCs组（P＜0.05），血清肌钙蛋白I（cTnI）、肌酸激酶同工酶（CK）-MB、白细胞介素（IL）-1α、IL-1β、IL-2、γ干扰素（IFN-γ）、IL-18水平以及脾脏组织CD40、CD86、CD80、MHC II、CD45RA、CD45RA+CD45RB，心脏组织NF-κB、NLRP3、半胱氨酸蛋白酶-1（Caspase）-1表达低于空白组、吗替麦考组、空白-BMSCs组（P＜0.05），血清IL-10、TGFβ1、TGFβ3水平以及脾脏组织CD274、Treg表达高于空白组、吗替麦考组、空白-BMSCs组（P＜0.05）。HE染色结果显示IDO组炎症细胞浸润较空白组、吗替麦考组、空白-BMSCs组明显减少。结论：过表达IDO-BMSCs可减轻免疫和炎症反应，改善移植心脏功能，可能与其抑制NF-κB/NLRP3信号通路的激活有关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) overexpressing indoleamine 2, 3-dioxygenase (IDO) on inflammatory response, T cell subsets and nuclear factor (NF) -κB/ nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3) pathway in abdominal ectopic heart transplantation model rats. Methods: Lentivirus vector and gene opening technique were used to construct the overexpressing IDO rat BMSCs, 60 rat models of abdominal ectopic heart transplantation were established, after successful modeling, and they were randomly divided into 4 groups, with 15 rats in each group. No treatment was given after the formation of the blank model, and the mycophenolate group was fed 40 mg/kg mycophenolate group, in the blank BMSCs group, blank BMSS was injected via tail vein 3 days after abdominal heterotopic heart transplantation, and in the IDO group, IDO BMSCs were overexpressed 3 days after abdominal heterotopic heart transplantation by tail vein injection (400 μL per animal. 106 cells). Cardiac function, serum myocardial enzymes, inflammatory factors, T cell subsets, cardiac pathological changes and NF-κB/NLRP3 pathway related protein expression were detected and compared in the four groups. Results: The ejection fraction difference and sequential shrinkage (FS) difference in the IDO group were higher than those in the blank group, mycophenolate group and blank-BMSCs group (P＜0.05). Serum troponin I (cTnI), creatine kinase isoenzyme (CK) -MB, interleukin(IL)-1α, IL-1β, IL-2, γ interferon(IFN-γ), and IL-18 levels, and spleen tissue CD40, CD86, CD80, MHCII, CD45RA, CD45RA combined CD45RB, heart tissue NF-κB, NLRP3, caspase-1 expressions were lower than those in blank group, mycophenolate group and blank-BMSCs group (P＜0.05). The serum IL-10, TGFβ1 and TGFβ1 levels, and the spleen tissue CD274 and Treg expressions were higher than those in the blank group, mycophenolate group and blank-BMSCs group(P＜0.05). HE staining showed that the inflammatory cell infiltration in the IDO group was significantly reduced compared with the blank group, mycophenolate group and blank-BMSCs group. Conclusion: The IDO-BMSCs overexpressing can reduce immune and inflammatory responses, and improve the function of transplanted heart, which may be related to its inhibition of the activation of NF-κB/NLRP3 signaling pathway. |
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