1,25(OH)_2D_3调控内质网稳态改善自发性糖尿病大鼠心肌损伤

1,25(OH)_2D_3 AMELIORATES DIABETIC MYOCARDIAL INJURY BY REGULATING ENDOPLASMIC RETICULUM HOMEOSTASIS

目的探讨1, 25(OH)_2D_3补充改善ZDF大鼠心肌损伤的潜在机制。方法健康雄性5～6 w龄Zucker瘦型鼠为正常对照组(C),胖型鼠按照体质量随机分为模型组(DM)、1, 25(OH)_2D_3低(DM+VD(L))、VD中(DM+VD(M))、高(DM+VD(H))剂量干预共4组。各组大鼠喂养至12 w龄,检测血糖血脂、心脏损伤及心肌细胞内质网应激相关指标。结果 DM组血脂、血糖显著升高,心肌出现严重损伤,内质网应激/未折叠蛋白反应标志蛋白GPR78显著降低,IRE1α-XBP1通路受阻;不同剂量1, 25(OH)_2D_3干预对ZDF大鼠血脂血糖及心肌损伤均有改善,其中、高剂量改善作用更为显著。1,25(OH)_2D_3低剂量干预未能显著改善ZDF大鼠未折叠蛋白反应的失活,1,25(OH)_2D_3中高剂量干预激活IRE1α-XBP1通路恢复内质网的稳态调节,中剂量的改善作用优于高剂量。结论适量的1,25(OH)_2D_3可通过IRE1α-XBP1通路调节内质网稳态,从而减轻糖尿病心肌损伤。[营养学报,2019,41(1):58-62]

Objective To investigate the potential protection of 1,25(OH)2D3 on type 2 diabetes mellitus induced myocardial damage.Methods Male Zucker lean rats(5-6 weeks)were assigned to control group(C).Male Zucker fatty rats(5-6 weeks)were randomly divided into 4 groups according to their body weight:T2 DM group(DM),low dose 1,25(OH)2D3 group supplementation(DM+VD(L)),middle dose 1,25(OH)2D3 group(DM+VD(M)),high dose 1,25(OH)2D3 group(DM+VD(H));All the rats were fed to 12 weeks of age.Serum glucose,heart injury and endoplasmic reticulum stress/unfolded protein response were measured.Results Compared with the control,serum glucose and TC of DM group rats were increased,and the cardiomyocytes were damaged,GRP78 was decreased and the IRE1α-XBP1 pathway was blocked.1,25(OH)2D3 supplementations decreased serum glucose and alleviated myocardial injury,in which the middle and high doses of 1,25(OH)2D3 supplementation were more effective.The middle and high doses of 1,25(OH)2D3 intervention activated IRE1α-XBP1 pathway to restore endoplasmic reticulum homeostasis,and the improvement effect of middle dose was better than that of high dose.Conclusion Appropriate amount of 1,25(OH)2D3 supplementation may attenuate diabetic myocardial injury by regulating endoplasmic reticulum homeostasis through activating IRE1α-XBP1 pathway.[ACTA NUTRIMENTA SINICA,2019,41(1):58-62]