运动和姜黄素对老年雄性大鼠心肌细胞与氧化应激和自噬相关的分子介质的影响。
Effect of exercise and curcumin on cardiomyocyte molecular mediators associated with oxidative stress and autophagy in aged male rats.
机构信息
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of anatomical sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
出版信息
Microvasc Res. 2022 Sep;143:104380. doi: 10.1016/j.mvr.2022.104380. Epub 2022 May 18.
AIM
Aging can origin changes in the heart that may increase risk of developing cardiovascular disease. This study aimed to characterize autophagy alterations and related molecular mediators in the heart tissue in the aging alone or in combination with exercise and curcumin treatment.
METHODS
Seven young and twenty-eight elderly male Wistar rats were assigned into five groups, namely: young control, age, exercise, curcumin, and curcumin+exercise. Aged rats in exercise group run on treadmill (17 m/min) and in the curcumin group received curcumin (50 mg/kg) by gavage daily for 8 weeks for 2 months. At the end, heart samples were collected and used for determination of autophagy by immunostaining for LC3-phosphatidylethanolamine conjugate (LC3-II), apoptosis by TUNEL assay, Malondialdehyde (MDA) level by enzymatic assay and determination of mediators' molecules by ELISA for NADPH Oxidase 4 (NOX4), sirtuin 1 (SIRT-1), phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-Ƙb) protein levels and Sequestosome-1 (P62). Also, histological changes such as fibrosis evaluated by Masson trichrome staining.
RESULTS
Our results showed that autophagy, SIRT-1 level were significantly decreased and MDA, NOX4, p-NF-Ƙb and P62 levels were significantly increased in heart of aged group compared to young group. Also, significant increased apoptosis and fibrosis levels in the heart of aged rats were observed compared with young rats, whereas, these undesirable changes were improved by exercise and curcumin. Also, combination therapy of aged rats with curcumin and exercise showed more significant prominent effect on molecular mediators and histological changes in the heart compared with monotherapy.
CONCLUSION
These findings indicate that stress oxidative increase and autophagy decrease in the heart tissue of aged rats. The age induced the mentioned changes in the heart may in part be associated with down-expression of SIRT-1 and overexpression of NOX4 proteins. It was also showed that these age induced effects can be alleviated by treatment with exercise and curcumin. Since NF-Ƙb increased in both the age and treatment groups, it seems the age heart increased NF-Ƙb to be due to a compensatory mechanism.
目的
衰老可引起心脏发生变化，从而增加患心血管疾病的风险。本研究旨在描述单纯衰老以及衰老合并运动和姜黄素治疗时心脏组织中自噬改变及其相关分子介质。
方法
将 7 只年轻雄性 Wistar 大鼠和 28 只老年雄性 Wistar 大鼠分为 5 组，即：年轻对照组、衰老组、运动组、姜黄素组和姜黄素+运动组。运动组的老年大鼠在跑步机上（17m/min）跑步，姜黄素组通过灌胃每天给予姜黄素（50mg/kg），持续 2 个月 8 周。最后，收集心脏样本，通过免疫组化检测 LC3 磷酸乙醇胺结合物（LC3-II）来检测自噬，通过 TUNEL 测定法检测凋亡，通过酶联免疫吸附试验测定丙二醛（MDA）水平，并通过酶联免疫吸附试验测定 NADPH 氧化酶 4（NOX4）、沉默调节蛋白 1（SIRT-1）、磷酸化核因子 kappa-轻链增强子的 B 细胞（p-NF-Ƙb）蛋白水平和自噬体相关蛋白 1（P62）等介质分子。此外，还通过 Masson 三色染色评估纤维化等组织学变化。
结果
与年轻组相比，衰老组心脏中的自噬和 SIRT-1 水平显著降低，MDA、NOX4、p-NF-Ƙb 和 P62 水平显著升高。与年轻大鼠相比，衰老大鼠心脏中的凋亡和纤维化水平显著升高，而运动和姜黄素治疗可改善这些不利变化。与单独治疗相比，衰老大鼠联合姜黄素和运动治疗对心脏中的分子介质和组织学变化显示出更显著的显著作用。
结论
这些发现表明，衰老大鼠心脏组织中的氧化应激增加和自噬减少。年龄引起的心脏变化可能部分与 SIRT-1 表达下调和 NOX4 蛋白表达上调有关。还表明，这些年龄引起的影响可以通过运动和姜黄素治疗来缓解。由于 NF-Ƙb 在年龄组和治疗组中均增加，因此衰老心脏中 NF-Ƙb 的增加似乎是由于代偿机制。
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