Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310007, P.R. China.
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11854. Epub 2021 Jan 26.
Allisartan isoproxil is a new nonpeptide angiotensin II receptor blocker (ARB) precursor drug that is used to treat hypertension and reduce the risk of heart disease. The present study explored the effects of allisartan isoproxil on diabetic cardiomyopathy (DCM) and revealed the roles of hyperglycaemia‑induced oxidative stress and inflammation. A rat DCM model was established by high‑fat diet feeding in combination with intraperitoneal injection of streptozocin. Echocardiographs showed that diabetic rats exhibited significantly decreased cardiac function. Troponin T (cTnT) and B‑type natriuretic peptide (BNP) were significantly increased in DCM rats as obtained by ELISA. Allisartan isoproxil significantly improved the EF% and E'/A' ratio. Histopathologic staining showed that allisartan isoproxil prevented histological alterations, attenuated the accumulation of collagen, and ameliorated cTnT and BNP levels. Western blot and immunohistochemical results indicated that the expression levels of silent information regulator 2 homologue 1 (SIRT1) and nuclear factor erythroid 2‑related factor 2 (Nrf2) were decreased in the hearts of diabetic rats, and antioxidant defences were also decreased. In addition, allisartan isoproxil decreased the expression of NF‑κB p65 and the inflammatory cytokines TNF‑α and IL‑1β which were determined by reverse transcription‑quantitative PCR in the diabetic heart. Western blotting and TUNEL staining results also showed that cardiac Bax and cleaved caspase‑3 and the number of apoptotic myocardial cells were increased in the diabetic heart and decreased following treatment with allisartan isoproxil. In conclusion, the present results indicated that allisartan isoproxil alleviated DCM by attenuating diabetes‑induced oxidative stress and inflammation through the SIRT1/Nrf2/NF‑κB signalling pathway.
奥美沙坦异丙酯是一种新型的非肽类血管紧张素 II 受体阻断剂（ARB）前药，用于治疗高血压和降低心脏病风险。本研究探讨了奥美沙坦异丙酯对糖尿病心肌病（DCM）的作用，并揭示了高血糖诱导的氧化应激和炎症的作用。通过高脂肪饮食喂养结合腹腔注射链脲佐菌素建立大鼠 DCM 模型。超声心动图显示糖尿病大鼠心脏功能明显下降。ELISA 检测结果显示 DCM 大鼠肌钙蛋白 T（cTnT）和 B 型利钠肽（BNP）明显升高。奥美沙坦异丙酯显著改善 EF%和 E'/A'比值。组织病理学染色显示奥美沙坦异丙酯可预防组织学改变，减少胶原积累，并改善 cTnT 和 BNP 水平。Western blot 和免疫组化结果表明，糖尿病大鼠心脏中沉默信息调节因子 2 同源物 1（SIRT1）和核因子红细胞 2 相关因子 2（Nrf2）的表达水平降低，抗氧化防御能力也降低。此外，奥美沙坦异丙酯通过逆转录-定量 PCR 降低了 NF-κB p65 以及炎性细胞因子 TNF-α和 IL-1β在糖尿病心脏中的表达。Western blot 和 TUNEL 染色结果也表明，糖尿病心脏中心肌 Bax 和 cleaved caspase-3 的表达以及凋亡心肌细胞的数量增加，而奥美沙坦异丙酯治疗后则减少。综上所述，本研究结果表明，奥美沙坦异丙酯通过 SIRT1/Nrf2/NF-κB 信号通路减轻糖尿病诱导的氧化应激和炎症，从而缓解 DCM。
