Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1-dependent mitochondrial oxidative damage.

BACKGROUND AND PURPOSE: Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin-1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin-1. EXPERIMENTAL APPROACH: I/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin-1 (sirtinol and SIRT1 siRNA). KEY RESULTS: In vivo and in vitro, icariin given before I/R significantly improved post-I/R heart contraction and limited the infarct size and leakage of creatine kinase-MB and LDH from the damaged myocardium. Icariin also attenuated I/R-induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn-superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin-1 was significantly up-regulated in hearts treated with icariin, whereas Ac-FOXO1 was simultaneously down-regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin-induced cardioprotection or disrupted icariin-mediated mitochondrial homeostasis. CONCLUSIONS AND IMPLICATIONS: Pretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.

[Experimental study on acute respiratory distress syndrome and analysis of relevant factors in rabbits subjected to thoracic blast trauma].

OBJECTIVE: To reproduce acute respiratory distress syndrome (ARDS) model in rabbit induced by chest blast injury and to analyze the pathogenesis and causes of early death in order to provide the basis for the early diagnosis of lung blast injury and its early warning system to facilitate an early treatment. METHODS: Sixty healthy New Zealand white rabbits were divided into six groups according to the different explosion distance with the random number table method. The survival rate and its resulting pathological changes were observed and patho physiological indexes and lung fluid content were determined at sequential time points post explosion. RESULTS: Shock wave pressure less than 1 210.5 mm Hg (1 mm Hg=0.133 kPa, group A, B) resulted in limited injury to the lung within grade 2 as assessed with the abbreviated injury scale (AIS). The rabbits in these groups recovered soon and survived without any complication. Shock pressure higher than 2 036.1 mm Hg (group D, E) caused severe injuries to the lung, including deep laceration , disruption of lung hilus and large hematoma in the lung, and the injury severity of lungs was assessed above grade 5 as assessed with AIS. All rabbits died within 1 hour post explosion. The groups described above failed to meet the demand of an ARDS model for the present study. Shock wave pressure at 1 917.3 mm Hg (group C) produced extensive contusion from grade 4 to grade 5 as assessed with AIS. The rabbits survived in poor general condition, and arterial partial pressure of oxygen (PaO(2)) lowered within 6 hours . Pathological examination showed extensive and constant multi focal bleeding involving more than four lobes. The alveolar wall was edematous, with partial rupture and alveolar fusion in lung tissues was observed in the group C. Alveoli were filled with inflammatory cells, and hyaline membrane was formed occasionally . Compared with control group, the wet to dry weight ratio (W/D) in lungs increased obviously (6.46±0.24 vs. 3.98±0.19, P<0.01) in group C within 6 hours postinjury. The contents of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in plasma and bronchoalveolar lavage fluid (BALF) were also increased distinctly compared with the control group [TNF-α (ng/L) in plasma: 328.89±6.26 vs. 62.12±2.98, TNF-α (ng/L) in BALF: 164.87±4.59 vs. 29.51±1.12; IL-6 (ng/L) in plasma: 128.51±4.13 vs. 19.32±1.53, IL-6 (ng/L) in BALF: 94.97±1.14 vs. 22.72±0.19, all P<0.05]. CONCLUSION: In an airtight environment, rabbit ARDS model can be reproduced successfully by blast injury with 1 917.3 mm Hg explosion pressure; TNF-α and IL-6 are involved in the pathogenesis and development of ARDS in blast injury. Pneumothorax as a result of lung rupture is the chief reason for early death and dysfunction of circulatory system is also an important reason in producing early death.