Astragaloside IV attenuates cardiac hypertrophy in rats born from mothers with intrauterine hypoxia through the PKC[beta]II/Egr-1 pathway

• Published in: Experimental and therapeutic medicine Vol. 26; no. 2
• Main Authors: Zhang, Ying, Wu, Mengqi, Deng, Yanbing, He, Baomei, Li, Hong
• Format: Journal Article
• Language: English
• Published: Spandidos Publications 01.08.2023
• Subjects: Astragalus (Plants); Care and treatment; Chemical properties; Complications and side effects; Development and progression; Diseases; Fetal anoxia; Health aspects; Heart enlargement; Infants (Newborn); Pediatric research; Physiological aspects; Phytochemicals; Protein kinases; Risk factors; Transcription factors; China
• ISSN: 1792-0981
• DOI: 10.3892/etm.2023.12064

Astragaloside IV (AS-IV) is a naturally occurring agent that confers several wide-ranging reported pharmacological effects, such as cardioprotective, antioxidative and pro-angiogenic activities. Although it was previously reported that AS-IV could attenuate neonatal rat myocardial ischemia-reperfusion injury, the possible effects of AS-IV on the development of cardiac hypertrophy associated with intrauterine hypoxia (IUH) remain unclear. The present study established a model of IHU by placing the pregnant rats in a plexiglass chamber with an oxygen supply of 10% before neonatal rat delivery. To investigate the in vivo effect of AS-IV on cardiac hypertrophy, neonatal rats with hypertension were randomly grouped to receive AS-IV (20 mg/kg), AS-IV (40 mg/kg), AS-IV (80 mg/kg) or vehicle for 12 weeks, followed by left ventricular (LV) hemodynamics and heart tissue histological analysis. Rats born from mothers with IHU displayed pathological features of cardiac hypertrophy. However, AS-IV 40 and 80 mg/kg significantly decreased the heart/body weight (BW), LV mass (LVM)/BW, heart mass/tibia length (TL) and LVM/TL ratios. H&E staining showed that 40 and 80 mg/kg AS-IV prevented the morphometric changes induced by IHU. According to data from LV hemodynamics measurements, AS-IV 80 mg/kg reversed the increased systolic blood pressure, diastolic blood pressure, LV systolic pressure, LV end-diastolic pressure, dP/dt maximum and heart rate induced by IHU. Mechanistically, ERK1/2 activation and early growth response 1 (Egr-1) protein expression were both upregulated by IHU induction, which was reversed by AS-IV treatment. In conclusion, these data suggested that AS-IV could attenuate cardiac hypertrophy in neonatal rats born from mothers with IHU through the protein kinase C [beta] type isoform 2/Egr-1 pathway, but the underlying mechanism requires further investigation. Key words: intrauterine hypoxia, cardiac hypertrophy, astragaloside IV, protein kinase C [beta] type isoform 2, early growth response 1