Diabetic cardiomyopathy (DCM) is considered to be a critical contributor to the development of heart failure. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has been shown to prevent cardiovascular events and reduce the incidence of heart failure in randomized clinical trials. However, the mechanism of how EMPA prevents DCM is poorly understood. To study the potential mechanisms involved in the therapeutic effects of EMPA, we assessed the protective effects of EMPA on myocardial injury in type 2 diabetic db/db mice and H9C2 cardiomyocytes. 9–10-week-old male db/db mice were treated with EMPA (10 mg/kg) via oral gavage daily for 20 weeks. Afterward, cardiac function of treated mice was evaluated by echocardiography, and pathological changes in heart tissues were determined by histopathological examination and western blot assay. EMPA markedly reduced blood glucose levels, improved insulin tolerance, and enhanced insulin sensitivity of db/db mice. In addition, EMPA significantly prevented cardiac dysfunction, inhibited cardiac hypertrophy and fibrosis, and reduced glycogen deposition in heart tissues. Furthermore, EMPA improved diabetes-induced oxidative stress and mitochondrial dysfunction in both heart tissues of db/db mice and palmitate exposed H9C2 cells. EMPA significantly increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream genetic targets in cardiac tissue of type 2 diabetic db/db mice and H9C2 cells. EMPA also downregulated the expression of mitochondrial fission-related proteins and upregulated the expression of mitochondrial fusion-related proteins. Collectively, these findings indicate that EMPA may prevent DCM via attenuating oxidative stress and improving mitochondrial function in heart tissue.
Didn't understand or not fully understand" is the most common situation that students experience when they learn medical biochemistry and molecular biology (MBMB). Therefore, the primary task of teaching MBMB is to help students overcome the difficulties in "conceptual understanding." The core of the solution to these problems lies in the acquisition and application of cognitive skills. The key to applying Ausubel cognitive assimilation theory (A's CAT) is to expand the knowledge capacity of students' cognitive structure through the purposeful "production" and employment of advanced organizers, with which students can replace "rote learning" with "meaningful learning" and ultimately develop an interest in MBMB courses. The results showed that the application of A's CAT did not only encourage the students to use cognitive skills to learn and understand MBMB knowledge and overcome the barrier to learning that results from the characteristics of the MBMB course, but also expanded and deepened the MBMB course contents. As a branch of learning theory, A's CAT provides practical methods for the several hypotheses of learning theory. Among these, the advanced organizer strategy realizes the organization and reorganization of new knowledge; the progressive differentiation strategy reduces the difficulty of complex and abstract knowledge; the implementation of the advanced organizer strategy and integrative reconciliation strategy forms the concept map. Taken together, the application of A's CAT includes cognitive strategy and metacognitive strategy when the cognitive process is conducted in a meaningful way. More importantly, application of A's CAT guides students to participate in active learning and builds "scaffolding" for the teaching/learning MBMB of student-centered goals.
K E Y W O R D SA's CAT, active learning, development of cognitive skills, learning theory, student-centered goals, teaching/learning MBMB Zhijie Tian and Kun Zhang contributed equally to this study.
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