Role of long non-coding RNA Kcnqlotl in mice with diabetic cardiomyopathy / 中国药理学通报

ABSTRACT

Aim To investigate the role of long noncoding RNA Kcnqlotl in mice with diabetic cardiomyopathy (DCM) and its mechanism. Methods C57BL/6 mice were divided into control group and diabetic group (DM). DM model was established by intraperitoneal injection of streptozocin. The DCM model was established by feeding for eight weeks. Kcnqlotl - shRNA lentivirus was injected to inhibit Kcnqlotl. The expression levels of Kcnqlotl in the left ventricle of mice in each group were detected by qRT-PCR. The function and structure of the left ventricular were evaluated using echocardiography, HE and Masson staining. The expression levels of collagen I, collagen M and TGF-β1/Smads signaling pathway were detected by Western blot. The expression levels of NLRP3, caspase-1, IL-1β and GSDMD-N in the left ventricular tissue of mice were detected by immunohistochemistry, qRT-PCR and Western blot. Results qRT-PCR showed that the expression of Kcnqlotl in the left ventricular tissues of diabetic mice significantly increased compared with the control group, and was significantly inhibited by Kcnqlotl-shRNA. The systolic and diastolic functions of diabetic hearts significantly decreased, and cardiomyocyte hypertrophy and myocardial fibrosis appeared as well. The cardiac function and structure of the diabetic mice were significantly improved, collagen expression levels were down-regulated and the TGF-β1/Smads pathways were inhibited after silencing Kcnqlotl. The expression levels of the pyroptosis related factors were down-regulated in the DM + Kcnqlotl-shRNA group. Conclusions The expression levels of IncRNA Kcnqlotl increase in the STZ-induced diabetic mice. Silencing Kcnqlotl can alleviate the pyroptosis and inhibit the TGF-β1/Smads pathway, thus ameliorating myocardial fibrosis.