[Knockout of PTEN improves cardiac function and inhibits NLRP3-mediated cardiomyocyte pyroptosis in rats with myocardial ischemia-reperfusion].

Objective To investigate the effects of phosphate and tension homology deleted on chromsome ten (PTEN) knockout on rat heart function and pyroptosis of cardiomyocytes mediated by NLR family pyrin domain containing 3 (NLRP3). Methods Rat models of myocardial ischemia/reperfusion (I/R) injury were established. The rats were divided into sham operation group (wild-type healthy rats), wild-type I/R group (wild-type healthy rats treated with myocardial I/R), and I/R group (PTEN KO rats treated with myocardial I/R). PTEN mRNA level was detected by reverse transcription PCR, and myocardial pathological damage was observed by HE staining. Heart rate (HR) and left ventricular wall thickness (LVWT) were measured by echocardiography, and left ventricular systolic blood pressure (LVSP), left ventricular ejection fraction (LVEF), and fraction shortening (FS) were recorded by BL-420F bioassay system. Serum creatine kinase isoenzyme (CK-MB), myoglobin (Mb) and cardiac troponin I (cTnI) were detected by ELISA. Western blot analysis was used to detect the protein expression of NLRP3, embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1), caspase-1 (caspase-1), and IL-1β in heart tissues. Immunohistochemical staining was performed to detect the content of caspase-1 in cardiac tissues. Apoptosis of myocardial tissue was observed with TUNEL staining. Results Compared with the sham operation group, PTEN mRNA and protein levels in the wild-type I/R group significantly increased, HR, LVSP, LVEF, FS, and LVWT went down significantly, and serum CK-MB, Mb, and cTnI levels significantly increased, and NLRP3, ELAVL1, caspase-1, and IL-1β protein expression levels went up significantly. After PTEN was knocked out, PTEN mRNA and protein levels were significantly reduced, the pathological damage of cardiomyocytes was alleviated, and HR, LVSP, LVEF, FS, and LVWT were significantly elevated, and serum CK-MB, Mb, and cTnI levels were significantly inhibited. NLRP3, ELAVL1, caspase-1, and IL-1β protein levels and the number of apoptotic cardiomyocytes were significantly reduced after PTEN knockout. Conclusion Knockout of PTEN can alleviate the pathological damage of myocardium and inhibit nlrp3-mediated apoptosis of cardiomyocytes, indicating that knockout of PTEN can alleviate myocardial I/R damage.