基于内质网应激-铁死亡途径探究甜茶素对妊娠期糖尿病大鼠心肌损伤的保护作用  

Rubusoside protects against myocardial injury in gestational diabetes mellitus rats via the endoplasmic reticulum stress-ferroptosis pathway

作　　者：袁银花 关琦 张珊珊 Yuan Yinhua;Guan Qi;Zhang Shanshan(Department of Obstetrics and Gynecology,Zhumadian Central Hospital,Zhumadian 463000,China)

机构地区：[1]驻马店市中心医院妇产科,驻马店463000

出　　处：《中华内分泌代谢杂志》2024年第11期956-965,共10页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的探究甜茶素(RS)对妊娠期糖尿病(GDM)大鼠心肌损伤的影响及可能作用机制。方法将SD孕鼠分为正常对照(Control)组、GDM模型(Model)组、胰岛素治疗(INS)组、RS组、内质网应激抑制剂4-苯基丁酸(4-PBA)组、RS+内质网应激诱导剂毒胡萝卜素(THA)组。干预后检测各组大鼠糖脂代谢水平及心功能指标;测定血清乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶MB(CK-MB)含量;观察心肌组织形态结构变化;检测心肌组织SOD、GSH、MDA、Fe^(2+)含量;DHE染色观察心肌组织ROS水平;普鲁士蓝染色观察心肌组织铁离子沉积情况;Western blot和免疫组化检测心肌组织内质网应激和铁死亡相关蛋白表达变化。结果与Control组相比, Model组大鼠体重、FBG、TC、TG升高, 心功能指标异常, 心肌出现明显的病理损伤, 血清LDH、cTnI、CK-MB水平增加, 心肌组织SOD、GSH活性降低, MDA、Fe^(2+)、ROS水平均增加, 可见明显的铁离子沉积, 心肌组织GRP78、CHOP、p-IRE1α、p-eIF2α和TFR1蛋白表达均升高, SLC7A11、GPX4蛋白表达均降低。与Model组相比, RS组和4-PBA组大鼠上述指标均得到显著性改变, 心肌损伤减轻。THA能够逆转RS对GDM大鼠内质网应激-铁死亡途径介导的心肌损伤保护作用。结论 RS能够有效改善GDM糖脂代谢功能, 减轻孕鼠心肌损伤, 其机制与抑制心肌内质网应激, 降低心肌细胞铁死亡有关。Objective To explore effect of rubusoside(RS)on myocardial injury in gestational diabetes mellitus(GDM)rats and its mechanism.Methods Pregnant SD rats were divided into control,GDM model,insulin treatment(INS),RS,endoplasmic reticulum stress inhibitor 4-phenylbutyric acid(4-PBA),and RS+endoplasmic reticulum stress inducer thapsigargin(THA)groups.Glycolipid metabolism,cardiac function,serum LDH,cTnI,and CK-MB levels,myocardial tissue morphology,SOD,GSH,MDA,Fe^(2+) content were assessed.ROS levels were assessed using DHE staining,and iron ion deposition was evaluated via Prussian blue staining.The expression of endoplasmic reticulum stress and ferroptosis related proteins in myocardial tissue after intervention was analyzed through Western blot and immunohistochemistry.Results Compared with control rats,GDM model rats showed increased body weight,FBG,TC,TG,abnormal cardiac function,significant myocardial damage,elevated serum LDH,cTnI,CK-MB,reduced SOD and CSH,increased MDA,Fe^(2+),ROS,and iron ions,along with altered protein expression indicating endoplasmic reticulum stress and ferroptosis.RS and 4-PBA mitigated these changes,reducing myocardial injury.THA reversed RS's protective effects via the endoplasmic reticulum stress-ferroptosis pathway.Conclusion RS improves glycolipid metabolism and alleviates myocardial injury in GDM rats by inhibiting endoplasmic reticulum stress and reducing ferroptosis.

关 键 词：妊娠期糖尿病 心肌损伤 甜茶素 内质网应激 铁死亡 

分 类 号：R714.256[医药卫生—妇产科学]