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松弛素-3 通过抑制内质网应激改善糖尿病心肌病。

Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress.

机构信息

Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

出版信息

Comput Math Methods Med. 2022 Sep 27;2022:9380283. doi: 10.1155/2022/9380283. eCollection 2022.

DOI:10.1155/2022/9380283
PMID:36203531
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9532149/
Abstract

BACKGROUND

This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS.

METHODS

Eighty male SD rats were randomly divided into two groups: controls ( = 20) and diabetes ( = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 g/kg/d), and high-dose relaxin-3 group (2 g/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1, and tumor necrosis factor (TNF)- were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis.

RESULTS

(1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls ( < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group ( < 0.05). (3) IL-17, IL-1, and TNF- levels in the DM rats at 4 weeks were higher than in the controls ( < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF- levels compared with the DM group at four and eight weeks ( < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls ( < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression.

CONCLUSIONS

Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.

摘要

背景

本研究旨在探讨松弛素-3 通过抑制 ERS 是否对糖尿病大鼠的心肌病具有保护作用。

方法

80 只雄性 SD 大鼠随机分为两组:对照组(n=20)和糖尿病组(n=60)。链脲佐菌素处理的大鼠随机分为三组:糖尿病组(DM)、低剂量松弛素-3 组(0.2g/kg/d)和高剂量松弛素-3 组(2g/kg/d)。通过苏木精和伊红(H&E)及 Masson 染色观察心肌组织和胶原纤维。通过 ELISA 测定血清脑钠肽(BNP)、肌钙蛋白(TNI)、肌红蛋白、白细胞介素(IL)-17、白细胞介素(IL)-1 和肿瘤坏死因子(TNF)-。通过 Western blot 分析检测各组心脏组织中葡萄糖调节蛋白 78(GRP78)和 C/EBP 同源蛋白(CHOP)的蛋白表达。

结果

(1)HE 和 Masson 染色表明松弛素-3 可减轻心肌病变和心肌胶原容积分数。(2)DM 组在四周和八周时的 BNP、TnI 和肌红蛋白均明显高于对照组(<0.01)。与 DM 组相比,松弛素-3 治疗组的血清 BNP、TnI 和肌红蛋白水平明显降低(<0.05)。(3)DM 大鼠在 4 周时的 IL-17、IL-1 和 TNF-水平高于对照组(<0.05)。低剂量或高剂量松弛素-3 治疗组在四周和八周时与 DM 组相比,血清 IL-17 和 TNF-水平降低(<0.05)。(4)DM 组在四周和八周时的 CHOP 和 GRP78 蛋白表达均高于对照组(<0.01),小剂量和大剂量松弛素-3 显著降低了 GRP78 和 CHOP 蛋白表达。

结论

外源性松弛素-3 通过抑制糖尿病大鼠的 ERS 改善糖尿病性心肌病。

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本文引用的文献

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Front Pharmacol. 2018 May 15;9:501. doi: 10.3389/fphar.2018.00501. eCollection 2018.
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Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy.诺米林可减轻链脲佐菌素诱导的糖尿病性心肌病中的心脏功能障碍、氧化应激和炎症反应。
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Valproate attenuates diabetic nephropathy through inhibition of endoplasmic reticulum stress‑induced apoptosis.
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Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses.线粒体功能与巨噬细胞甾醇代谢及炎症反应的调节
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H2 and H3 relaxin inhibit high glucose-induced apoptosis in neonatal rat ventricular myocytes.H2和H3松弛素抑制新生大鼠心室肌细胞中高糖诱导的细胞凋亡。
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Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy.糖尿病性心肌病中的内质网应激与蛋白质质量控制
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Reduced endoplasmic reticulum stress might alter the course of heart failure via caspase-12 and JNK pathways.内质网应激减少可能通过半胱天冬酶-12 和 JNK 途径改变心力衰竭的进程。
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