The Effects And Mechanisms Of Curcumin On Rat Ischemia-reperfusion Induced Lung Injury

Partâ… : The effects and mechanism of preischemic treatment with curcumin on lung warm ischemia-reperfusion injury in ratsObjective: Based on the known properties of curcumin (CUR) and dexamethasone (DXM) to inhibit inflammation and oxidative stress. The present study aims at investigating potential effects of CUR and DXM on ischemia-reperfusion (IR) induced lung injury in rats.Methods: Sham-operated rats were used as time-matched controls. Experimental rats were subjected to left lung hilus clamping with 90 minutes ischemia followed by 4 hours reperfusion. Animals were randomly pretreated with a single intraperitoneal dose of vehicle, CUR (50mg/kg or 200mg/kg) or DXM (5mg/kg) 2 h before anesthesia, respectively.Results: In vivo, IR induced lung injury was characterized by an increased microvascular permeability and myeloperoxidase (MPO) activity and decreased levels of arterial oxygen tension/inspired oxygen concentration ratio. Pretreatment with CUR (200 mg /kg) or DXM markedly attenuated IR induced barrier disruption, lung edema, tissue inflammation, and decreased PO₂ at 4 hours after reperfusion. Nuclear factor-κB (NF-kB) in reperfused lungs was activated, accompanied with increased levels of tumor necrosis factor (TNF)-αand interleukin (IL)-1β. Increased lipid peroxidation and xanthine oxidase (XO) activity and decreased total anti-oxidative capability (TAOC) were also observed in reperfused lungs.The increases in NF-kB, inflammatory cytokines, MPO and malondialdehyde (MDA) were significantly suppressed by administration of CUR (200 mg /kg) or DXM. The changes in XO activity and TAOC were only significantly prevented by pretreatment with CUR (200 mg /kg).Conclusions: Pretreatment with CUR has protevtive effects on IR induced lung injury, similar to steroid. CUR attenuates acute lung injury probably through improving oxidative stress and inhibiting NF-kB mediated expression of inflammatory cytokines. Thus, CUR may be an alternative therapeutic strategy for improving the outcome of IR induced lung injury. Partâ…¡: Curcumin improves matrix metalloproteinase correlated alveolar-capillary permeability alteration in rat models of warm ischemia reperfusion injuryObjective: Matrix metalloproteinases (MMPs) are able to degrade the endothelial basal lamina and increase vascular permeability.The present study aims at investigating the relationship of MMPs expression and alveolar capillary membrane permeability in rat models of warm ischemia reperfusion lung injury (IRI).Methods: Sham-operated rats were used as time-matched controls, experimental rats were randomly assigned to vehicle-untreated, curcumin (CUR)-treated groups. The left lungs of rats were rendered ischemic for 90 min by clamping the left pulmonary hilum and then reperfused for 1h or 4h. Histologic changes of the lung, wet/dry weight ratio, arterial oxygen tension/inspired oxygen concentration ratio, lung microvascular permeability, NF-kB activity, MMP9 and MMP2 mRNA expression and their activity in reperfused lungs were examined.Results: Compared to sham values, the alveolar capillary-membrane permeability evaluated by the Evans blue dye (EBD), was increased 2．3-fold and 3．8-fold after 1 h and 4 h of reperfusion, respectively. MMP9 mRNA levels and protein activity were activated 1 h after reperfusion, were further increased after 4 h of reperfusion. And this increase correlated with the EBD content. MMP2 mRNA levels were activated 4 h after reperfusion, no significant differences in the MMP2 activity were observed among either group. The increase in MMP9 mRNA expression and activity was significantly suppressed by CUR, and CUR pretreatment significantly reduced IR induced barrier disruption.Conclusions: MMP9, but not MMP2, mainly correlates with the alteration of alveolar-capillary permeability in the early stage of IR-induced lung injury. CUR attenuates lung barrier disruption from IRI by suppressing NF-KB-mediated expression of MMP9． 鈽匬art鈪? The effects and mechanism of preischemic treatment with curcumin on lung transplantation-associated lung Injury in rats鈽匫bjective: Curcumin (CUR) and dexamethasone (DXM) have been found to inhibit the development of inflammation and oxidative stress. The present study aims at investigating potential effects of curcumin or DXM on lung transplantation-associated lung injury.鈽匨ethods: Sham-operated rats were used as time-matched controls. Experimental rats were subjected to unilateral orthotopic lung transplantation with a 4h cold ischemia followed by a 2h or 24h reperfusion. Animals were randomly assigned to vehicle-treated, CUR or DXM-treated groups.鈽匯esults: In vivo, transplantation induced lung injury with profound increases in graft Evan's blue content, wet/dry weight ratio and myeloperoxidase levels, accompanied by a decrease in the arterial oxygen tension/inspired oxygen concentration ratio. Pretreatment with CUR and DXM significantly prevented from barrier disruption, lung edema, tissue inflammation, and decreased PaO₂ at the early stage of post-transplantation. Nuclear factor-魏B (NF-kB ) in transplanted lungs was activated, accompanied by an increase in mRNA levels of tumor necrosis factor (TNF)-伪, interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 and protein content in lung graft. Those changes were prevented by pretreatment with CUR and DXM.鈽匔onclusions: CUR can be a new therapy for protecting lung transplantation-associated injury in the early postoperative period after lung transplantation by suppressing NF-魏B-mediated expression of inflammatory genes.