Ginkgo biloba extract(EGb 761) attenuates lung injury induced by intestinal ischemia/reperfusion in rats:Roles of oxidative stress and nitric oxide

AIM： To investigate the effect of ginkgo biloba extract （EGb 761） on lung injury induced by intestinal ischemia/ reperfusion （ Ⅱ/R）. METHODS： The rat model of Ⅱ/R injury was produced by damping the superior mesenteric artery for 60 min followed by reperfusion for 180 min. The rats were randomly allocated into sham, Ⅱ/R, and EGb ＋Ⅱ/R groups. In EGb ＋Ⅱ/R group, EGb 761 （100 mg/kg per day） was given via a gastric tube for 7 consecutive days prior to surgery. Rats in Ⅱ/R and sham groups were treated with equal volumes of the vehicle of EGb 761. Lung injury was assessed by light microscopy, wet-todry lung weight ratio （W/D） and pulmonary permeability index （PPT）. The levels of malondialdehyde （MDA） and nitrite/nitrate （NO2/NO3）, as well as the activities of superoxide dismutase （SOD） and myeloperoxidase （MPO） were examined. Western blot was used to determine the expression of inducible nitric oxide synthase （iNOS）. RESULTS： EGb 761 markedly improved mean arterial pressure and attenuated lung injury, manifested by the improvement of histological changes and significant decreases of pulmonary W/D and PPT （P 〈 0.05 or 0.01）.Moreover, EGb 761 markedly increased SOD activity, reduced MDA levels and MPO activity, and suppressed NO generation accompanied by down-regulation of iNOS expression （P 〈 0.05 or 0.01）. CONCLUSION： The results indicate that EGb 761 has a protective effect on lung injury induced by Ⅱ /R, which may be related to its antioxidant property and suppressions of neutrophil accumulation and iNOS- induced NO generation. EGb 761 seems to be an effective therapeutic agent for critically ill patients with respiratory failure related to Ⅱ/R.

Dingxin Recipe(定心方) Prevents Ischemia/Reperfusion-Induced Arrhythmias via Up-regulating Prohibitin and Suppressing Inflammatory Responses

Objective： To identify the underlying mechanisms of the protective effects of Dingxin Recipe （定心方, DXR）, a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion （I/R）-induced arrhythmias in rat model. Methods： A total of 30 rats were randomly divided into three groups： sham group, I/R group, and DXR-pretreated I/R （DXR-I/R） group. Rats in the DXR- I/R group were intragastrically administrated with DXR （12.5 g/kg per day） for consecutive 7 days, while rats in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms （ECG） were recorded. Two-dimensional （2-D） polyacrylamide gel electrophoresis and matrix- assisted laser desorption ionization time-of-flight mass spectrometry （MALDI-TOF MS） were used to identify differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction （RQ- PCR）, Western blot, and enzyme-linked immunosorbent assay （ELISA） were performed to analyze proteins obtained in the above experiments. Results： DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin （PHB） and heart fatty acid binding protein （hFABP） were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione （GSH） was elevated accompanied by reduced expressions of interleukin-6 （IL-6） and neutrophil infiltration in I/R rats with DXR pretreatment. Conclusions： DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.