辣椒素对造血干细胞稳态的影响  

Effect of capsaicin on hematopoietic stem cell quiescence in mice

作　　者：曾浩[1] 胡梦佳 汤勇[1] 芦玉凯 陈默[1] 王军平[1] ZENG Hao;HU Mengjia;TANG Yong;LU Yukai;CHEN Mo;WANG Junping(State Key Laboratory of Trauma,Burns and Combined Injury,Institute of Combined Injury,Faculty of Military Preventive Medicine,Army Medical University（Third Military Medical University）,Chongqing,400038,China)

机构地区：[1]陆军军医大学(第三军医大学)军事预防医学系全军复合伤研究所,创伤、烧伤与复合伤国家重点实验室

出　　处：《第三军医大学学报》2018年第22期2021-2026,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81573084);重庆市科技创新领军人才支持计划(CSTCKJCXLJRC06)~~

摘　　要：目的 观察辣椒素对造血干细胞稳态的影响,并初步探讨其相关机制。方法 采用8～10周龄C57BL/6J小鼠,按随机数字表法分成实验组和对照组,分别给予0. 4 mg/d辣椒素溶液和单纯溶剂灌胃建立动物模型。采用流式细胞术检测造血干细胞稳态变化。利用流式分选得到原代造血干细胞进行q-PCR,分析周期相关蛋白激酶CDK2、CDK6 mRNA表达水平。利用CD45. 1小鼠作为受体进行造血移植实验。结果 流式细胞术分析结果显示,实验组造血干/祖细胞（LSK）比例较对照组明显升高[（0. 299±0. 041）%vs（0. 177±0. 052）%,P 〈0. 01]。亚群分析显示,与对照组比较,实验组短期造血干细胞（ST-HSC）比例上升[（47. 48±3. 22）%vs（37. 63±1. 85）%,P 〈0. 01],造血祖细胞（MPP）比例下降[（40. 59±3. 04）%vs（50. 12±1. 95）%,P 〈0. 01]。周期分析结果显示,与对照组比较,实验组造血干/祖细胞增殖,G0期细胞数目下降。q-PCR结果也证实实验组CDK2、CDK6 mRNA表达增强。凋亡和竞争性骨髓移植结果两组差异无统计学意义（P〉 0. 05）。结论 辣椒素促进造血干细胞增殖,灌胃辣椒素能致短期造血功能增强。Objective To study the effect of capsaicin on the quiescence of hematopoietic stem cells （HSCs） and explore the underlying mechanisms. Methods C57BL/6J mice （8 - 10 weeks old） were randomized for daily intragastric administration of 0. 4 mg capsaicin solution or PBS for over 4 weeks. Flow cytometry was used to detect the changes in the HSCs. Fluorescence-activated cell sorting was employed to acquire the primary HSCs for analysis of cycle-related protein kinase CDK2 and CDK6 mRNA expression levels using real-time quantitative PCR （q-PCR）. The whole bone marrow cells from capsaicin- or PBS-treated mice were transplanted in mixture with the recipient bone marrow cells in CD45. 1 mice, and the hematopoietic capacity of the transplanted HSCs were assessed at different time points after the transplantation. Results Flow cytometry analysis showed that capsaicin treatment for over 4 weeks resulted in a significantly increased percentage of hematopoietic stem/ progenitor （LSK） cells in the hone marrow monocytes as compared with PBS treatment [ （0. 299 ± 0. 041 ） % vs （0. 177 ±0. 052） %, P 〈 0.01 ]. Subpopulation analysis of the LSK cells showed that compared with PBS treatment, capsaicin treatment significantly increased the percentage of short-term HSCs [ （47.48 ± 3.22） % vs （37.63 ±1. 85） %, P 〈 0.01 ] and decreased the percentage of the hematopoietic progenitor （MPP） cells [ （40.59 ± 3.04 ） % vs （50.12± 1.95 ） %, P 〈 0.01 ], suggesting the enhanced hematopoietic function in eapsaicin-treated mice. Cell cycle analysis showed obvious proliferation of LSK cells and a reduction in the Go cells. The results of q-PCR also confirmed the up-regulation of CDK2 and CDK6 mRNA levels in the LSK cells from capsaicin-treated mice. In the cell apoptosis test and competitive bone marrow transplantation experiment, no obvious difference was found between capsaicin and PBS treatment groups, indicating that capsaicin did not affect the long-term hematopoietic capacity of the HSCs.

关 键 词：辣椒素 造血干细胞 增殖 干细胞稳态 

分 类 号：R285.5[医药卫生—中药学] R322.2[医药卫生—中医学]