Wang Hong-Wei, Chen Yi-He, Chen Yan-Yan, Huang Wei, Zhu Xian-Dong, Ni Fu-Biao, Wu Guo-Di, Xu Zi-Qiang, Huang Zhou-Qing, Chen Bi-Cheng, Xiao Fang-Yi
Department of Hepatobiliary and Pancreatic Surgery Laboratory, The First Affiliated Hospital of Wenzhou Medical University Nanbaixiang, Wenzhou 325000, Zhejiang, China.
Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University Nanbaixiang, Wenzhou 325000, Zhejiang, China.
Am J Transl Res. 2018 Aug 15;10(8):2445-2456. eCollection 2018.
Although islet transplantation has been identified as a promising endocrine replacement treatment for patient with diabetes mellitus (DM), it still remains unclear whether islet transplantation can inhibit the diabetic-induced myocardial injury and subsequent adverse ventricular remodeling. Here, we sought to explore the molecular mechanism underlying the cardioprotective effect of islet transplantation. We established the diabetic rat model by intraperitoneal injection of STZ, which was followed by either islet transplantation or conventional insulin treatment. Compared with insulin treatment, islet transplantation further reduced the elevated blood glucose which was nearly restored to normoglycaemia. In addition, islet transplantation attenuated the increased levels of cTn-I and CK-MB, cleaved-caspase-3 in response to DM, and ameliorated diabetic-induced cardiac hypertrophy and interstitial fibrosis, along with improved extracellular matrix (ECM) deposition. Moreover, diabetic rats that underwent islet transplantation had lower expression of TGF-β1 and lower phosphorylation levels of Smad3. Therefore, islet transplantation exerted protective effect against diabetic-induced myocardial injury and fibrotic remodeling through deactivation of TGF-β/Smad3 signaling pathway.
尽管胰岛移植已被确认为糖尿病患者一种有前景的内分泌替代治疗方法，但胰岛移植是否能够抑制糖尿病诱导的心肌损伤及随后的不良心室重构仍不清楚。在此，我们试图探究胰岛移植心脏保护作用的分子机制。我们通过腹腔注射链脲佐菌素建立糖尿病大鼠模型，随后进行胰岛移植或常规胰岛素治疗。与胰岛素治疗相比，胰岛移植进一步降低了升高的血糖，血糖几乎恢复到正常水平。此外，胰岛移植减轻了糖尿病引起的cTn-I和CK-MB水平升高、cleaved-caspase-3水平升高，并改善了糖尿病诱导的心脏肥大和间质纤维化，同时改善了细胞外基质（ECM）沉积。此外，接受胰岛移植的糖尿病大鼠TGF-β1表达较低，Smad3磷酸化水平较低。因此，胰岛移植通过使TGF-β/Smad3信号通路失活，对糖尿病诱导的心肌损伤和纤维化重构发挥保护作用。
