浙江大学学报(医学版)2025,Vol.54Issue(3):318-332,15.DOI:10.3724/zdxbyxb-2024-0700
韭菜子等补肾中药促进雷帕霉素诱导的急性退化胸腺再生
Effects of kidney-tonifying Chinese herbs on thymus regene-ration after rapamycin-induced degeneration in mice
摘要
Abstract
Objective:To investigate the effect of a variety of kidney-tonifying Chinese medicines on thymus regeneration after acute degeneration in mice.Methods:Forty-eight 8-week-old male BALB/c mice were randomly divided into normal control group,model control group,negative control group,positive control group,the fructus of Cnidium monnieri(L.)Cuss.group,the fructus of Psoralea corylifolia(L.)group,the fructus of Rubus chingii Hu group,and the tuber onion seed group,with 6 mice in each group.Except for the normal control group,mice in the other groups received intraperitoneal injections of rapamycin(1 mg·kg-1·d-1)for 5 consecutive days followed by 14 h of starvation to induce acute thymus degeneration.After successful modeling,in treatment groups ethanol extract of the fructus of Cnidium monnieri(L.)Cuss.(0.78 g·kg-1·d-1),fructus of Psoralea corylifolia(L.)(0.39 g·kg-1·d-1),fructus of Rubus chingii Hu(0.78 g·kg-1·d-1)or the tuber onion seed(0.39 g·kg-1·d-1)was intraperitoneally injected once a day for 5 days;while the negative control group was given equal volume of normal saline,and the positive control group was given metformin(300 mg·kg-1·d-1).The grip strength was measured with a grip tester 2 h after the last administration.The pathological changes of thymus were observed by hematoxylin and eosin(HE)staining.The structure and distribution of thymic epithelial cells were observed by multiple immunofluorescence method.The proportion of T cell subsets in thymus and peripheral blood was analyzed by flow cytometry.The level of T cell receptor excision circles(TREC)in the genomic DNA of mouse spleen mononuclear cells was detected by quantitative polymerase chain reaction(PCR)for evaluation of thymic output function.The expression of thymus aging-and function-related factors in the thymus tissue were detected by quantitative reverse transcription PCR.The expression of cyclin-dependent kinase inhibitor 1A(p21)and tumor protein 53(p53)were verified by immunohistochemistry.Results:Rapamycin induced thymic atrophy and significantly reduced limb grip strength in mice(P<0.01).Compared with the negative control group,the limb grip strength of mice in the fructus of Psoralea corylifolia(L.)group,the fructus of Rubus chingii Hu group and the tuber onion seed group was significantly enhanced(all P<0.05),and the level of TREC in spleen of the mice in each administration group was reduced(all P<0.05).Among Chinese herb medicine-treatment groups,the recovery of thymus function and tissue structure in the tuber onion seed group was most obvious.Further study showed that compared with the negative control group,the proportion of CD4 single positive cells(CD3+TCR-β+CD4+CD8-)in the thymus of the tuber onion seed group was significantly increased(P<0.01),and the proportion of CD3+CD28+T cell and CD3+CD8+CD28+T cell in peripheral blood was significantly increased(all P<0.01).The mRNA levels of IL-1α,IL-6,p21 and p53 in thymocytes were decreased(all P<0.05).The results of immunohistochemistry further confirmed the decrease in p21 and p53 expression.In normal mice,tuber onion seed was observed to enhance limb grip strength(P<0.01),while suppressing thymus output and change the distribution of T cell subsets,and there was no significant effect on thymus weight and the expression of Foxn1,SIRT1,p21,CXCL2 and PTMα.Conclusion:The tuber onion seed and other kidney-tonifying traditional Chinese medicines can accelerate the regeneration process of mouse thymus after acute degeneration induced by rapamycin in mice,and the tuber onion seed exhibits the most pronounced therapeutic effect.关键词
补肾中药/韭菜子/胸腺/再生/抗衰老/小鼠Key words
Kidney-tonifying Chinese medicine/Tuber onion seed/Thymus/Regeneration/Anti-aging/Mice分类
医药卫生引用本文复制引用
温许诺,周玫汝,张凤婕,舒耀莹,高建莉..韭菜子等补肾中药促进雷帕霉素诱导的急性退化胸腺再生[J].浙江大学学报(医学版),2025,54(3):318-332,15.基金项目
国家自然科学基金(82274621) The study was supported by the National Natural Science Foundation of China(82274621). (82274621)