Dai Xianliang, Zhao Jian, Hua Li, Chen Hui, Liang Chun
Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China; Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
Int Immunopharmacol. 2023 Mar;116:109798. doi: 10.1016/j.intimp.2023.109798. Epub 2023 Feb 2.
Previous studies have found that thymus is involved in the process of hypertension. However, whether thymus transplantation alleviates target organ damage in hypertensive mice remains unknown. The aim of this study was to evaluate the effects of thymus transplantation on blood pressure and target organ changes in mice with hypertension. Mice were randomly divided into normal control group (Con), hypertensive group (HTN) and thymus transplantation group (HTN + Trans). Thymus of neonatal mice was transplanted into the renal capsule of the transplantation group. After transplantation, the mouse tail noninvasive pressure was measured and heart function was evaluated weekly. Then mice were euthanized and organs or tissues were harvested at 4 weeks post-transplantation. The blood pressure of HTN + Trans group was lower than that in the HTN group. The expression of FoxN1, Aire, ATRAP, thymosin β4 and the content of sjTREC in thymus of HTN group was decreased and the number of naïve T cells in HTN group was lower compared with other two groups. The ratio of cTEC/mTEC in HTN group was higher than that in Con group and lower than that in HTN + Trans group. Cardiac pathology showed cardiac hypertrophy and fibrosis in HTN group whereas thymus transplantation improved heart function and structure. Altogether, our findings demonstrated thymus transplantation could improve thymus function of hypertensive mice, which increased the expression of thymus transcription factor FoxN1, affected the proportion of T cell subsets, and increased thymosin β4 thereby reducing blood pressure and reversing the progression of target organ damage.
先前的研究发现胸腺参与了高血压的发生过程。然而,胸腺移植是否能减轻高血压小鼠的靶器官损伤仍不清楚。本研究的目的是评估胸腺移植对高血压小鼠血压和靶器官变化的影响。将小鼠随机分为正常对照组(Con)、高血压组(HTN)和胸腺移植组(HTN + Trans)。将新生小鼠的胸腺移植到移植组的肾包膜内。移植后,每周测量小鼠尾无创血压并评估心脏功能。然后在移植后4周对小鼠实施安乐死并采集器官或组织。HTN + Trans组的血压低于HTN组。HTN组胸腺中FoxN1、Aire、ATRAP、胸腺素β4的表达及sjTREC的含量降低,且HTN组的初始T细胞数量低于其他两组。HTN组cTEC/mTEC的比例高于Con组且低于HTN + Trans组。心脏病理学检查显示HTN组存在心脏肥大和纤维化,而胸腺移植改善了心脏功能和结构。总之,我们的研究结果表明胸腺移植可改善高血压小鼠的胸腺功能,增加胸腺转录因子FoxN1的表达,影响T细胞亚群比例,并增加胸腺素β4,从而降低血压并逆转靶器官损伤的进展。