肌肽对高糖诱导的心肌成纤维细胞增殖的影响  

Effect of carnosine on cell proliferation in rat cardiac flbroblasts induced by high glucose and its mechanism

作　　者：毕惠梅[1] 王利华 崔云霞[3] 周宏博[3] Bi Huimei Wang Lihua Cui Yunxia Zhou Hongbo(Clinical laboratory of Heilongjiang agricultural Reclamation Bureau General Hospital ,Harbin 150088, China （Bi HM Department of the Second Breathing, Heilongjiang Infectious Disease Hospital for Control and Prevention, Harbin 150500, China （ Wang LH Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China （ Cui YX , Zhou HB)

机构地区：[1]黑龙江省农垦总局总医院检验科,哈尔滨150088 [2]黑龙江省传染病防治院内八科,哈尔滨150500 [3]哈尔滨医科大学生物化学与分子生物学教研室,150081

出　　处：《国际免疫学杂志》2017年第5期497-501,共5页International Journal of Immunology

摘　　要：目的 研究肌肽（carnosine）对高糖环境下大鼠心脏成纤维细胞（cardiac flbroblasts，CFs）增殖的影响及机制。方法 以CFs为研究对象，使用Brdu-酶联免疫吸附试验（enzyme-linked immunosorbent assays，ELISA）检测法观察肌肽抑制高糖环境下心肌成纤维细胞DNA的合成；细胞周期的测定采用流式细胞仪法；Western blot法观察不同条件下CFs中CDK2、CyclinE、PCNA、ERK1/2、p-ERK1/2及p21和p27的蛋白表达情况。结果 肌肽能够抑制高糖环境下CFs的DNA合成，通过调节细胞周期和细胞周期的相关蛋白表达来实现这种作用。与高糖组比较，20 mmol/L肌肽组明显抑制了高糖刺激的大鼠CFs中CDK2、CyclinE、PCNA蛋白的表达增加（tCDK2＝6.19、tCyclinE＝5.7、tPCNA＝8.56，P〈0.05），差异具有统计学意义；与高糖组比较20 mmol/L肌肽则使p21、p27表达水平增加了（tp21＝5.16、tp27＝8.558，P〈0.05），具有统计学意义；与高糖组比较20 mmol/L的肌肽或20 mol/L的PD-98059（ERK1/2抑制剂）明显抑制了高糖刺激的大鼠CFs中p-ERK1/2的表达增加（t肌肽＝5.64、tPD＝8.68，P〈0.05），差异具有统计学意义。结论 肌肽能够通过ERK1/2 MAPK信号通路抑制高糖环境下心肌成纤维细胞的DNA合成。Objective To study the effect of carnosine on the proliferation of rat cardiac flbroblasts（CFs） induced by high glucose. Methods CFs were used in this experiment.Brdu-enzyme-linked immunosorbent assays（ELISA） was used to observe CF DNA synthesis induced by high glucose.The cell cycle was determined by flow cytometry.In addition, Western blot method was used to observe the expression level of cell cycle proteins including p21, p27, cyclinE, and CDK2.MAPK pathways related proteins ERK1/2 and p-ERK1/2 were also determined.Results Carnosine can significantly inhibit DNA synthesis of CFs induced by high glucose, we found that 20 mmol/L carnosine prevented the increase of cyclin E, CDK2 and PCNA expression（tCDK2=6.19、tCyclinE=5.7、tPCNA=8.56, P〈0.05） and counteracted the reduced expression of p27 and p21 induced by high glucose（tp21=5.16、tp27=8.558, P〈0.05）. In addition, ERK1/2 signaling took part in the proliferation process and regulated the expression of the cell cycle proteins（t肌肽=5.64、tPD=8.68, P〈0.05）.Conclusions Carnosine can inhibit proliferation of CFs by high glucose.The mechanism on carnosine’s inhibition could be related to ERK1/2MAPK pathways.

关 键 词：肌肽 高糖 心肌成纤维细胞 细胞增殖 

分 类 号：R542.2[医药卫生—心血管疾病] R587.2[医药卫生—内科学]