利格列汀和胰岛素联合治疗对1型糖尿病小鼠心脏未折叠蛋白反应的评价。

Züleyha Doğanyiğit, Aslı Okan, Serpil Taheri, Zeynep Yılmaz, Enes Akyüz, Necdet Demir
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摘要

本研究的目的是揭示利格列汀(一种DPP-4抑制剂,由于其有益的心血管作用)对内质网应激(ERS)信号传导的影响,该信号传导参与了与1型糖尿病相关的心血管并发症的发病机制。BALB/c雌性小鼠(n = 72)分为6组:对照组、糖尿病+胰岛素组、糖尿病+利格列汀组、糖尿病+TUDCA组和糖尿病+TUDCA+胰岛素组。免疫组织化学和蛋白质印迹法、qRT-PCR、ELISA法和丙二醛(MDA)测定。给予1型糖尿病小鼠心脏的利那列汀显著降低了ATF6、ATF4和p-JNK、胱天蛋白酶3的总形式和裂解形式的表达水平。免疫组织化学和蛋白质印迹分析显示,与其他组相比,糖尿病+胰岛素组中裂解的胱天蛋白酶3蛋白表达显著增加。根据ELISA结果,TUDCA在降低NOX1和MDA水平方面比利格列汀更有效。虽然利格列汀降低了Chop mRNA水平,但Grp78 mRNA水平没有变化。我们的研究结果表明,利格列汀单独给药或与胰岛素联合给药之间没有太大差异。我们的研究表明,利格列汀是治疗1型糖尿病心脏ERS和凋亡UPR的有效药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Evaluation of linagliptin and insulin combined therapy on unfolded protein response in type 1 diabetic mouse heart

Evaluation of linagliptin and insulin combined therapy on unfolded protein response in type 1 diabetic mouse heart

The aim of this study is to reveal the effects of the use of linagliptin, a DPP-4 inhibitor due to its beneficial cardiovascular effects, on endoplasmic reticulum stress (ERS) signaling, which is involved in the pathogenesis of cardiovascular complications related to type 1 diabetes. BALB/c female mice (n = 72) were divided into six groups: control, diabetes+insulin, diabetes+linagliptin, diabetes+linagliptin+insulin, diabetes+TUDCA, and diabetes+TUDCA+insulin. Immunohistochemistry and western blot method, qRT-PCR, ELISA method, and malondialdehyde (MDA) measurements were performed. Linagliptin administered to the type 1 diabetic mouse heart significantly reduced the expression levels of the total and cleaved forms of ATF6, ATF4, and p-JNK, caspase 3. Immunohistochemical and western blot analyses revealed that cleaved caspase 3 protein expression was significantly increased in the diabetes+insulin group compared to the other groups. According to ELISA findings, TUDCA was more effective in reducing NOX 1 and MDA levels than linagliptin. While linagliptin decreased the Chop mRNA level, no change was observed in the Grp78 mRNA level. Our findings showed that there was not much difference between the administration of linagliptin alone or in combination with insulin. Our study reveals that linagliptin is an effective therapeutic agent on ERS and apoptotic UPR in type 1 diabetic hearts.

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