姜黄素逆转慢性阻塞性肺疾病糖皮质激素抵抗的作用机制  

Mechanism of curcumin reversing glucocorticoid resistance in chronic obstructive pulmonary disease

作　　者：张文路[1] 何志义[1] 赵琳[1] 宾雁飞[1] 

机构地区：[1]广西医科大学第一附属医院,南宁530021

出　　处：《山东医药》2016年第38期1-4,共4页Shandong Medical Journal

基　　金：广西医科大学青年科学基金项目(GXMUYSF201332)

摘　　要：目的观察姜黄素通过抑制磷酸化细胞外调节蛋白激酶(p-ERK)促进组蛋白去乙酰酶2(HDAC2)蛋白表达,探讨姜黄素逆转慢性阻塞性肺疾病(COPD)患者糖皮质激素抵抗的可能机制。方法选取人单核系细胞白血病细胞U937为研究对象,MTT法测定细胞增殖活性,绘制增殖曲线判断细胞生长状态;以0、20、40、80μmol/L的姜黄素作用U937细胞6、12、24 h,MTT法测定细胞活性,确定姜黄素作用浓度及时间;将对数生长期的U937细胞分为两组,干预组以MTT实验确定的姜黄素浓度及作用时间培养,对照组不处理,采用Western blot法检测pERK及HDAC2蛋白。结果 U937细胞增殖曲线近似S形,表明该细胞株生长状态良好,可用于后续实验;随着姜黄素浓度的增加及作用时间的延长,U937细胞活性逐渐减低,确定姜黄素干预浓度及时间为40μmol/L和12 h。对照组与干预组细胞中p-ERK蛋白相对表达量分别为0.848±0.033、0.359±0.035,HDAC2蛋白相对表达量分别为0.258±0.009、0.525±0.032,差异具有统计学意义(P均<0.05)。结论姜黄素能够通过抑制p-ERK促进HDAC2蛋白表达,这可能是姜黄素逆转COPD患者糖皮质激素抵抗的机制之一。Objective To observe curcumin promoting histone deacetylase 2 （HDAC2） protein expression through restrai- ning phosphorylation of extracellular protein kinase （p-ERK） and clarify the possible mechanism of curcumin reversing glucocor- ticoid resistance in chronic obstructive pulmonary disease （COPD）. Methods U937 cells were selected. MTT was used to detect the proliferation activity and then we drew the curve to determine cell growth condition. We used 0, 20, 40 and 80 μmol/L curcumin to treat U937 cell for 6, 12 and 24 h, then determined the cell activity by MTr to determine the concentration and time of curcumin. Cells in the logarithmic phase were divided into two groups. The intervention group was treated with the determined concentration and action time of curcumin. Western blotting was used to detect p-ERK and HDAC2 protein. Results The cell proliferation curve of U937 was similar to S type, showing that the cells were in good condition and could be used in next test. With increasing concentration and extending time of curcumin, U937 cell activity gradually reduced, and the determined concen- tration and time was 40 μmol/L and 12 h. The relative expression of p-ERK protein in the control group and intervention group was respectively 0. 848±0. 033 and 0.359±0.035 ; and the relative expression of HDAC2 protein was 0.258 ±0.009 and 0. 525± 0. 032, respectively （all P 〈 0. 05 ）. Conclusion Curcumin could promote HDAC2 protein expression by inhibiting p-ERK, which may be one of the mechanisms of curcumin reversing glucocortieoid resistance.

关 键 词：慢性阻塞性肺疾病 姜黄素 糖皮质激素抵抗 U937细胞 组蛋白去乙酰酶2 磷酸化细胞外调节蛋白激酶 

分 类 号：R563[医药卫生—呼吸系统]