Abstract
ObjectiveTo investigate the ameliorative effect of Semaglutide-loaded PEG-nanoliposomes (Sem-PEG-lips) combined with ultrasound-targeted microbubble destruction (UTMD) on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM) in rodents and its potential mechanisms. MethodsSem-PEG-lips were prepared by the reverse phase evaporation method. Fifty STZ-induced diabetic rats were randomly divided into DCM model group, Sem or Sem-PEG-lips alone treatment group, UTMD + Sem group and UTMD + Sem-PEG-lips group (n = 10), respectively, and used the healthy rats as normal control. During the 12-week intervention, the weight and blood glucose levels of all rats were recorded. Myocardial injury and fibrosis were observed by using H&E and Masson staining. The activity of antioxidant enzymes and the expression levels of oxidative stress-related signaling pathway markers in myocardial tissues were measured by ELISA and western blotting method, respectively. ResultsCompared with DCM rats, the body weight and blood glucose levels of those in the UTMD + Sem-PEG-lips group were significantly increased and decreased, respectively (both p < 0.05). The results of H&E and Masson staining showed that myocardial fibrosis and apoptosis were both significantly improved in combination group (both p < 0.001). Further results of ELISA and Western blot analysis showed that the activity of antioxidant enzymes in ones received combination therapy were significantly higher than that in DCM model group (all p < 0.001), and the expression of PI3K/Akt/Nrf2 signaling pathway related proteins were significantly up-regulated (all p < 0.001), and all these changes were reversed by the treatment of PI3K inhibitor. results ConclusionUTMD combined Sem-PEG-lips can reduce the oxidative stress of myocardial tissue in DCM rats by activating PI3K/Akt/Nrf2 signaling pathway, thereby improving diabetic myocardial injury.
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