Xu Qian, Ding Huanxin, Li Songhan, Dong Shuohui, Li Linchuan, Shi Bowen, Zhong Mingwei, Zhang Guangyong
Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
Front Physiol. 2021 Nov 11;12:785799. doi: 10.3389/fphys.2021.785799. eCollection 2021.
Cardiac hypertrophy as a main pathological manifestation of diabetic cardiomyopathy (DCM), is a significant complication of diabetes. Bariatric surgery has been proven to relieve DCM; however, whether it can alleviate diabetes-induced cardiac hypertrophy is undefined. Diabetic and obese rats were performed sleeve gastrectomy (SG) after having diabetes for 16weeks. The rats were euthanized 8weeks after SG. Metabolic parameters, heart function parameters, myocardial glucose uptake, morphometric and histological changes, and the expression level of mitogen-activated protein kinases (MAPKs) were determined and compared among the control group (CON group), diabetes mellitus group (DM group), sham operation group (SHAM group), and SG group. Compared with the SHAM group, the blood glucose, body weight, insulin resistance, and other metabolic parameters were significantly improved in the SG group. There was also a marked improvement in myocardial morphometric and histological parameters after SG. Furthermore, the myocardial glucose uptake and heart function were reversed after SG. Additionally, the phosphorylation of MAPKs was inhibited after SG, including p38 MAPKs, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases 1/2 (ERK1/2). The expression of DUSP6, which dephosphorylates ERK1/2, was upregulated after SG. These findings suggest that SG ameliorated diabetes-induced cardiac hypertrophy correlates with the MAPK signaling pathway. These results showed that diabetes-induced cardiac hypertrophy was ameliorated after SG was closely related to the inhibition of the MAPK signaling pathway and upregulation of DUSP6. Therefore, this study provides a novel strategy for treating diabetes-induced cardiac hypertrophy.
心脏肥大作为糖尿病性心肌病（DCM）的主要病理表现，是糖尿病的一种重要并发症。减重手术已被证明可缓解DCM；然而，其是否能减轻糖尿病诱导的心脏肥大尚不清楚。糖尿病和肥胖大鼠在患糖尿病16周后进行袖状胃切除术（SG）。SG术后8周对大鼠实施安乐死。测定并比较了对照组（CON组）、糖尿病组（DM组）、假手术组（SHAM组）和SG组的代谢参数、心功能参数、心肌葡萄糖摄取、形态学和组织学变化以及丝裂原活化蛋白激酶（MAPK）的表达水平。与SHAM组相比，SG组的血糖、体重、胰岛素抵抗和其他代谢参数均有显著改善。SG术后心肌形态学和组织学参数也有明显改善。此外，SG术后心肌葡萄糖摄取和心功能得到逆转。另外，SG术后MAPK的磷酸化受到抑制，包括p38 MAPK、c-Jun氨基末端激酶（JNK）和细胞外信号调节激酶1/2（ERK1/2）。使ERK1/2去磷酸化的双特异性磷酸酶6（DUSP6）的表达在SG术后上调。这些发现表明，SG改善糖尿病诱导的心脏肥大与MAPK信号通路相关。这些结果表明，SG术后糖尿病诱导的心脏肥大得到改善与MAPK信号通路的抑制和DUSP6的上调密切相关。因此，本研究为治疗糖尿病诱导的心脏肥大提供了一种新策略。
