ABSTRACT
The protective effects of cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPTP), on vascular permeability in sepsis rats were investigated. Cecal ligation and puncture (CLP)-induced sepsis rats were used for in vivo studies, and the effects of CsA (1 and 5 mg·kg-1) on vascular permeability of lung, kidney, and intestine, mitochondrial respiratory control ratio, and the survival of the sepsis rats were observed. Lipopolysaccharide (LPS) was used for stimulating vascular endothelial cells (VECs) in vitro, and the effects of CsA on leakage of microvascular, immunofluorescence of zonula occludes-1 (ZO-1), and transendothelial electrical resistance (TER) were observed. All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of the Army Medical University. Compared with sham-operated group, the vascular permeability of lung, kidney, and intestine in sepsis rats increased significantly (P<0.05). Compared with conventional treatment group, CsA could significantly decrease the vascular permeability of lung, kidney, and intestine (P<0.05 or P<0.01), and prolong the survival period. The results of microcirculation also showed that CsA could significantly reduce the permeability of mesenteric venules in sepsis rats. At the cellular level, LPS stimulation significantly increased the permeability of vascular endothelial cells, including the decrease of transmembrane resistance and protein expression of ZO-1 (P<0.05). CsA can significantly reduce the increase of permeability of vascular endothelial cells induced by LPS stimulation (P<0.01). The function of mitochondria in the kidneys and intestines of sepsis rats was obviously impaired, and the respiratory control ratio of mitochondria was decreased. LPS significantly increased MPTP opening of VECs, while CsA significantly inhibited MPTP opening and improved mitochondrial function. CsA may protect mitochondrial function by inhibiting the opening of MPTP and play a protective role in the vascular permeability of sepsis rats. This study will provide an insight for the treatment of sepsis vascular leakage.
ABSTRACT
Objective To compare the difference in cardiac injuries between asphyxia and ventricular fibrillation modes in different periods after cardiac arrest (CA).Methods The model was established in Cardiopulmonary Resuscitation Lab,Sun Yat-sen University.A total of 35 male SD rats were used to produce the asphyxia or ventricular fibrillation (VF) cardiac arrest models randomly.Both of the two modes were induced 8 minutes cardiac arrest.The myocardial HE stains,mitochondrial respiratory control ratio (RCR),and echocardiography were observed at 4 h,24 h and 72 h after ROSC (restoration of spontaneous circulation).The results were expressed as (-x ± s),t test was performed to compare between two groups,and one way analysis of variance was used to compare multiple groups.P ＜ 0.05 was considered as significant difference.Results HE stains showed damages were more serious in the VF mode than in asphyxia mode at 4 h,and both of them had a disorderly-arranged myocardium at 72 h.RCR in VF mode became worse at 4 h,and RCR resumed at 24 h in both modes without significant difference compared with the sham operated rats.The echocardiography showed VF mode had a lower left ventricular ejection fraction (LVEF) than asphyxia mode at 4 h (29.68％ vs.42.16％,P =0.03),and there was no difference in LVEF between VF mode and the sham operated rats at 24 h,however no difference in LVEF between the asphyxia and sham operated rats at 72 h.Both of them had a thicker left ventricular anterior wall than the sham operated rats at 72 h (2.41 mm vs.1.72 mm,P=0.013; 2.61 mmvs.1.72 mm,P=0.007),and there was no significant difference between them.Conclusions The ventricular fibrillation mode has a more severe injuries in early period,but it recovers sooner than asphyxia one.Both of two groups get compensatory left ventricular hypertrophy in later period of ROSC.
ABSTRACT
Using succinate as a substrate,the respiratory control ratio (RCR) of liver mito-chondria of 20 burned Sprague-Dawley rats (male, 20%of burned body surface area, III degree burn), and 32 burned Wistar rats (male), increased 30 minutes and 2 hours after burn, and ADP/O ratio increased 39 minutes after burn. But ADP/O ratio decreased and RCR was nearly normal 4 hours after burn.The observations suggest that there is an increasing mitochondria coupling during the early phase of burn injury, which has not been reported.