背景:心脏肥大(CH)是发病和死亡的原因之一。高同型半胱氨酸血症(HHcy)是可能导致高脂血症和CH的疾病之一。已知利格列汀(Linagliptin,利纳)和谢奥异瑞辛醇二葡糖苷(SDG)通过减少氧化应激和炎症来缓解多种疾病。目的:本研究旨在研究HHcy对心脏组织的影响,特别关注内质网(ER)应激作为主要病理生理途径。此外,我们的研究检查了莉娜的保护作用,SDG,以及它们的组合对抗HHcy诱导的大鼠高脂血症和CH。方法:雄性SD大鼠75只,随机分为5组,60天,给予以下方案:I组:大鼠接受蒸馏水;II组:大鼠接受蛋氨酸(MET)(2g/kg/天,p.o.);第III和IV组:大鼠接受了Lina(3mg/kg/天,p.o.)和SDG(20mg/kg/天,p.o.),分别,其次是MET(2g/kg/天,p.o.);第V组:大鼠接受莉娜和SDG,其次是MET(2g/kg/天,p.o.).结果:用丽娜预处理,SDG,与MET组相比,它们的组合显示血清HHcy水平显着降低,血脂状况改善。此外,两种药物都能改善心脏损伤,心电图参数的大幅改善证明了这一点,心肌的形态特征,和降低心脏标志物的血清水平。此外,莉娜和SDG显著减弱心脏氧化应激,炎症,和凋亡。此外,莉娜,SDG,它们的组合显著下调内质网(ER)应激标志物的表达增强,GRP78PERK,ATF-4,CHOP,NF-κB,和SREBP1c与MET组相比。结论:丽娜和SDG对HHcy诱导的大鼠心肌肥厚和高脂血症具有保护作用。
Background: Cardiac hypertrophy (CH) is one of the contributing causes of morbidity and mortality. Hyperhomocysteinemia (HHcy) is one of the diseases which may predispose hyperlipidemia and CH. Linagliptin (Lina) and secoisolariciresinol diglucoside (SDG) are known to alleviate a variety of illnesses by reducing oxidative stress and inflammation. Aim: This study aimed to study the effect of HHcy on cardiac tissues, with a special focus on endoplasmic reticulum (ER) stress as a mainstay pathophysiological pathway. In addition, our study examined the protective effect of Lina, SDG, and their combination against HHcy-induced hyperlipidemia and CH in rats. Methods: Seventy-five male Sprague-Dawley rats were randomly divided into five groups, and for 60 days, the following regimen was administered: Group I: rats received distilled water; Group II: rats received methionine (MET) (2 g/kg/day, p.o.); groups III and IV: rats received Lina (3 mg/kg/day, p.o.) and SDG (20 mg/kg/day, p.o.), respectively, followed by MET (2 g/kg/day, p.o.); Group V: rats received Lina and SDG, followed by MET (2 g/kg/day, p.o.). Results: Pretreatment with Lina, SDG, and their combination showed a significant decrease in serum levels of HHcy and an improved lipid profile compared to the MET group. Moreover, both drugs improved cardiac injury, as evidenced by the substantial improvement in ECG parameters, morphological features of the cardiac muscle, and reduced serum levels of cardiac markers. Additionally, Lina and SDG significantly attenuated cardiac oxidative stress, inflammation, and apoptosis. Furthermore, Lina, SDG, and their combination remarkably downregulated the enhanced expression of endoplasmic reticulum (ER) stress markers, GRP78, PERK, ATF-4, CHOP, NF-κB, and SREBP1c compared to the MET-group. Conclusion: Lina and SDG showed cardioprotective effects against HHcy-induced heart hypertrophy and hyperlipidemia in rats.