Objective To study the protective effects of propofol against ischemia/reperfusion injury in rat lung. Methods Rat model of pulmonary ischemia/reperfusion injury was used in this study. Rats were randomly divided into three groups, including sham opera-tion group (group A), iachemia/reperfusion group (group B) and propofol group (group C), 15 rats in each group. The concentration of tumor necrosis factor -α and interleukin-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). Then blood gas analysis, lung wet/dry (W/D) weight ratio were detected in each group. Results Propofol could significantly improve PaO2, reduce the W/D value and the contents of TNF-α and IL-6 in BALF. Conclusion Propofol effectively suppressed the pro-duction and release of inflammatory cytokine, therefore it can protect the lung from isehemia/reperfusion injury.

OBJECTIVE: To elucidate the effects of mammalian sterile 20-like kinase 1 (MST1) gene on tumor necrosis factor (TNF)-α-mediated human umbilical vein endothelial cell (HUVEC) apoptosis. METHODS: Cultured HUVECs were treated with either vehicle or TNF-α (1-100 ng/mL) for 24 hours. Cell apoptosis was measured by TUNEL staining, and MST1 activity was analyzed by Western blot. In order to knock down MST1 expression in HUVECs, cells were transfected with 100 nmol/L MST1 small interference RNA (siRNA) using Lipofectamine 2000 for 24 hours, and the transfection efficiency was analyzed by Western blot. MST1 siRNA-transfected cells were treated with 10 ng/mL TNF-α for an additional 24 hours. Cell apoptosis was measured by TUNEL staining and caspase-3 activity was detected by Western blot. RESULTS: MST1 activity was stimulated in a dose-dependent manner after TNF-α treatment (10, 40, 100 ng/mL) and reached the maximal effect at 100 ng/mL. MST1 activity also paralleled the onset of apoptosis as determined by TUNEL staining (P<0.001). Transfection with MST1 siRNA markedly diminished MST1 gene expression in a dose-dependent manner. MST1 siRNA (100 nmol/L) significantly silenced MST1 gene (P<0.05) and reduced TNF-α-induced endothelial cells apoptosis (P<0.05) by way of inhibiting MST1 gene activation and, accordingly, suppressing caspase-3 activity. CONCLUSION Silencing of MST1 expression by siRNA diminishes TNF-α-mediated human umbilical vein endothelial cell apoptosis by inhibiting the cascade effect of caspase-3.
Apoptosis ; genetics ; Cells, Cultured ; Hepatocyte Growth Factor ; genetics ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Proto-Oncogene Proteins ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVE: To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms.
 METHODS: Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min-
reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC.
 RESULTS: At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ.
 CONCLUSION RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.
Animals ; Autophagy ; drug effects ; genetics ; physiology ; Extremities ; Interleukin-10 ; metabolism ; Interleukin-6 ; metabolism ; Ischemia ; Ischemic Preconditioning ; methods ; Liver ; injuries ; Liver Diseases ; prevention & control ; Oxidative Stress ; drug effects ; PPAR gamma ; antagonists & inhibitors ; Rats ; Reperfusion Injury ; prevention & control ; Tumor Necrosis Factor-alpha ; metabolism