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高血糖通过HBP途径增加SD大鼠子宫内膜细胞内β-catenin稳定性

Glucose enhances the stability of β-catenin via hexosamine biosynthetic pathway in endometrium of SD rats
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摘要 目的:探讨高血糖通过HBP途径增加子宫内膜细胞内β-catenin稳定性的相关机制。方法50只SD雌性大鼠随机分为正常对照组、禁食组、高糖高脂组、葡萄糖胺组和葡萄糖组。高糖高脂组给予高糖高脂饲料喂养,其他组普通饲料喂养。8周后将高糖高脂组和正常对照组大鼠处死;禁食组禁食24h后处死;葡萄糖胺组禁食24h后给予葡萄糖胺2.50g/kg灌胃,3h后处死;葡萄糖组禁食24 h后给予葡萄糖5 g/kg灌胃,3 h后处死。分别取各组大鼠子宫内膜组织,检测相关蛋白和基因表达水平。结果 HSHF组和NC组相比,各饲养周空腹血糖水平均明显升高(t值2.34~2.78,均P<0.05)。 GLU组和FASTING组相比,血糖水平明显升高(t=3.46,P<0.05),而GLN组和FASTING组相比血糖水平无统计学差异(t=0.84,P>0.05)。 Western blot检测结果相对表达量分析显示, GLN组和GLU组子宫内膜组织内β-catenin、O-GlcNAc表达量均明显高于FASTING组( t值3.44~5.08,均P<0.05),而GLN组和GLU组之间β-catenin、O-GlcNAc表达量均无统计学差异(t值分别为0.75、0.66,均P>0.05)。 RT-PCR检测HSHF组Ctnnb1表达水平与NC组相比无统计学差异(t =0.43,P>0.05),而β-catenin特异性靶基因CyclinD1和Axin2表达水平HSHF组明显高于NC组(t值分别为4.48、5.26,均P<0.05)。结论高血糖能够通过HBP途径,使β-catenin的O-GlcNAc化增加,从而增加其稳定性,使进入细胞核内的β-catenin增多,持续作用于下游靶基因引起细胞异常增殖分化。 Objective To investigate the mechanism of hyperglycemia enhancing the stability of β-catenin in endometrial cells via hexosamin biosynthetic pathyway (HBP).Methods Female SD rats were randomly divided into 5 groups: normal control (NC) group, fasting ( FASTING) group, high sugar and high fat ( HSHF) group, glucosamine ( GLN) group and glucose ( GLU) group.Rats in the HSHF group were given high glucose and high fat diet , while the other groups were given normal diet .After 8 weeks’ feeding rats in HSHF group and NC group were executed and endometrium of them were collected .Rats in FASTING group were executed after 24h.GLN group and GLU group was lavaged with glucosamine (2.50g/kg) and glucose (5g/kg) after fasting for 24 hours.Three hours later the rats were executed.Then endometrium of rats in each gorup was collected to detect expressions of protein and genes .Results Compared with NC group, fasting blood glucose level increased remarkably in HSHF group (t value ranged 2.34 -2.78, both P〈0.05).Compared with FASTING group, glucose level of GLU group enhanced significantly (t=3.46,P〈0.05), but GLN group was not significantly different (t=0.84,P〉0.05).Western blot detection results showed that the expressions of β-catenin and O-GlcNAc in GLN group and GLU group were remarkably higher than those in FASTING group (t value ranged 3.44-5.08, respectively, all P〈0.05), but the differences in GLN group and GLU group were not significant (t value was 0.75 and 0.66, respectively, both P〉0.05).RT-PCR detetion revealed that the difference in Ctnnb1 expression was not significant between HSHF group and NC group (t=0.43, P〉0.05), but the expressions of CyclinD1 and Axin2 were remarkably higher in HSHF group than in NC group (t value was 4.48 and 5.26, respectively, both P〈0.05). Conclusion Hyperglycemia can enhance O-GlcNAc level of β-catenin via HBP , and thus elevate its stability to help the accululation of β-catenin, which causes abnormal proliferation by consitent action on downstream target genes .
出处 《中国妇幼健康研究》 2016年第1期14-17,共4页 Chinese Journal of Woman and Child Health Research
关键词 高血糖 内膜癌 WNT/Β-CATENIN O-GLCNAC hyperglycemia endometrial cancer WNT/β-catenin O-GlcNAc
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