ABSTRACT
Celastrol, extracted from Tripterygium wilfordii, is a natural pentacyclic triterpene compound, which has an anti-pulmonary fibrosis effect. However, its effect, binding targets and regulatory mechanism in pulmonary fibroblasts remain unclear. In this study, we found that celastrol could prevent fibroblast-myofibroblast transformation (FMT) by significantly inhibiting transforming growth factor β1 (TGFβ1)-induced α-smooth muscle actin and type I collagen expression. Previous studies suggested that heat shock protein 60 (HSP60) may be the target of celastrol. This study confirmed the direct interaction between celastrol and HSP60 through cellular thermal shift assay and surface plasmon resonance experiment, and demonstrated that the KD value of celastrol binding to HSP60 was 8.59 μmol·L-1. Further studies showed that knockdown of HSP60 promoted TGFβ1-induced FMT, especially in the medium and low dose TGFβ1 treatment group, and that the anti-FMT effect of celastrol was significantly weakened after HSP60 knockdown. These results indicated that HSP60 was involved in maintaining the resting state of fibroblasts, and the anti-FMT effect of celastrol was dependent on HSP60. Furthermore, the autophagy promotion and antioxidant effects of celastrol were also weakened after HSP60 knockdown. In conclusion, celastrol inhibits FMT by targeting HSP60, thus exerting anti-pulmonary fibrosis function.
ABSTRACT
Objective: to compare the ventilatory effects of the three-way laryngeal mask airway [TLMA] and tracheal tube [TT] on hemodynamics, respiratory function, and stress responses in a canine model during bronchoalveolar lavage [BAL]
Study Design: experimental study
Place and Duration of Study: the 303rd Hospital of the Chinese People's Liberation Army in May 2013
Methodology: sixteen dogs were divided into two groups. MAP, SpO[2] and HR were recorded before anesthesia [T[0]], immediately before intubation [T[1]], during intubation [T[2]], at 3 [T[3]] and 10 [T4] minutes after mechanical ventilation, at 10 [T[5]], 20 [T[6]], and 30 [T[7]] minutes during the course of BAL, during extubation [T[8]], and 3 minutes after extubation [T[9]]. Tidal volume, peak inspiratory airway pressure, and expiratory CO[2] pressure were recorded at time points T[2], T[5], T[6], T[7], and T[8]. Stress responses variables, including epinephrine and norepinephrine levels, were examined at time points T[0], T[2], T[3], T[5], T[8], and T[9]
Results: BAL was successfully completed in all animals. In comparison to the TT, the TLMA was capable of maintaining hemodynamic stability and ventilation [p < 0.05], and producing less stress responses [p < 0.05]
Conclusion: in a canine model, ventilation with the TLMA was better than the TT during BAL in terms of maintaining effective ventilation and stable hemodynamics, and producing less stress responses