不同中医证型骨髓增生异常综合征患者自噬性组蛋白密码的差异性研究  

Differences in autophagic histone code in patients with myelodysplastic syndrome of different traditional Chinese medicine syndromes

作　　者：梁陈慧 陶雨晨 陆嘉惠[1] LIANG Chenhui;TAO Yuchen;LU Jiahui(Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China)

机构地区：[1]上海中医药大学附属市中医医院,上海200071

出　　处：《上海中医药杂志》2023年第4期51-56,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81873286);上海市科委上海市优秀学术带头人计划项目(20XD1403500);上海市科委医学创新研究专项重大项目(21Y31920400);上海市卫健委上海市卫生系统优秀人才培养计划项目(2018BR15);上海申康医院发展中心临床科技创新项目(SHDC12020128)。

摘　　要：目的研究不同中医证型骨髓增生异常综合征(MDS)患者自噬性组蛋白密码表达的差异性。方法根据相关标准将MDS患者分为正虚毒蕴组、毒盛正虚组,将健康人群设为健康对照组,采用激光扫描共聚焦显微镜观察比较各组骨髓单个核细胞(BMMNCs)自噬囊泡,流式细胞术检测BMMNCs自噬水平,Western blot法检测BMMNCs组蛋白密码表达情况。结果(1)与健康对照组比较,正虚毒蕴组、毒盛正虚组BMMNCs自噬囊泡数量减少(P<0.05);与正虚毒蕴组比较,毒盛正虚组BMMNCs自噬囊泡数量进一步减少(P<0.05)。(2)与健康对照组比较,正虚毒蕴组BMMNCs的甲基化修饰[组蛋白H3亚基27号赖氨酸甲基化(H3K27me)、组蛋白H4亚基16号赖氨酸甲基化(H4K16me)]表达水平升高(P<0.05),乙酰化修饰[组蛋白H3亚基4号赖氨酸乙酰化(H3K4ac)、组蛋白H3亚基9号赖氨酸乙酰化(H3K9ac)]表达水平降低(P<0.05),毒盛正虚组BMMNCs的H3不同位点及H4位点的甲基化修饰水平升高(P<0.05),乙酰化修饰[H3K4ac、H3K9ac、组蛋白H3亚基27号赖氨酸乙酰化(H3K27ac)、组蛋白H3亚基56号赖氨酸乙酰化(H3K56ac)、组蛋白H4亚基16号赖氨酸乙酰化(H4K16ac)]表达水平降低(P<0.05)。结论MDS患者与正常人群BMMNCs自噬水平及组蛋白修饰水平表达存在差异,H3不同位点及H4位点的高甲基化及低乙酰化水平会通过下调细胞自噬水平参与MDS的发生、发展。Objective To study the difference of autophagy histone code expression in myelodysplastic syndrome(MDS)patients with different traditional Chinese medicine(TCM)syndromes.Methods According to the relevant criteria,MDS patients were divided into healthy qi deficiency and toxin accumulation(HQDTA)group,toxin exuberance and healthy qi deficiency(TEHQD)group,and healthy people were set as the healthy control group.The laser scanning confocal microscope was employed to observe and compare the autophagic vesicles of bone marrow mononuclear cells(BMMNCs)in each group,flow cytometry was used to detect the autophagic level of BMMNCs,and Western blot was used to detect the histone code expression of BMMNCs.Results①The number of autophagic vesicles of BMMNCs decreased in the HQDTA group and TEHQD group compared with that in the healthy control group(P<0.05).The number of autophagic vesicles of BMMNCs was further reduced in the TEHQD group compared with that in the HQDTA group(P<0.05).②Compared with those in the healthy control group,the expression levels of methylation modifications(H3K27me,H4K16me)of BMMNCs increased(P<0.05)and the expression levels of acetylation modifications(H3K4ac,H3K9ac)of BMMNCs decreased(P<0.05)in the HQDTA group.Compared with those in the healthy control group,the expression levels of methylation modifications of different H3 and H4 sites of BMMNCs increased(P<0.05)and the expression levels of acetylation modifications(H3K4ac,H3K9ac,H3K27ac,H3K56ac,H4K16ac)decreased(P<0.05)in the TEHQD group.Conclusions The autophagy levels and histone modification levels of BMMNCs are different between MDS patients and healthy people.The high methylation and low acetylation levels at different sites of H3 and H4 participate in the development and progression of MDS by down-regulating the cellular autophagy levels.

关 键 词：骨髓增生异常综合征 白血病 中医证型 自噬 组蛋白 

分 类 号：R259[医药卫生—中西医结合]