Effects of penehyclidine hydrochloride on myocardial ischaemia-reperfusion injury in rats by inhibiting TLR4/MyD88/NF-κB pathway via miR-199a-3p

Growth Factors. 2022 Nov;40(5-6):186-199. doi: 10.1080/08977194.2022.2109469. Epub 2022 Aug 19.

Abstract

This study was to probe the role of penehyclidine hydrochloride (PHC) mediating the impact of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signalling pathway on myocardial ischaemia-reperfusion injury (MI/RI) in rats through miR-199a-3p. The rat MI/RI model was established through ligating left anterior descending (LAD) coronary artery. PHC was injected preoperatively into the model rats, and injected with miR-199a-3p lentiviral vector or TLR4 antagonist (TAK-242). Next, cardiac function of rats was examined by echocardiography, and rat serum indicators, oxidative stress levels and inflammatory factors were detected. HE staining was applied to detect pathological tissue structure, TUNEL staining to detect apoptosis rate, qRCR and western blot to detect miR-199a-3p and TLR4/MyD88/NF-κB expressions in rat myocardial tissues. Dual luciferase reporter experiment was conducted to confirm the relationship between miR-199a-3p and TLR4. In conclusion, PHC suppresses TLR4/MyD88/NF-κB signalling pathway through miR-199a-3p, thereby improving MI/RI in rats.

Keywords: Penehyclidine; improving; miR-199a-3p; myocardial ischaemia-reperfusion.

MeSH terms

  • Animals
  • Disease Models, Animal
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardial Reperfusion Injury* / genetics
  • NF-kappa B / metabolism
  • Rats
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • NF-kappa B
  • Toll-Like Receptor 4
  • Myeloid Differentiation Factor 88
  • penehyclidine
  • MicroRNAs
  • Tlr4 protein, rat
  • Myd88 protein, rat