| Objective:The standardized extract of the leaves of Gingko biloba, EGb 761, a mixture mainly composed of flavanoid glycosides and terpene lactones, has been shown to exhibit a variety of pharmacological actions. It's the most commonly prescribed herbal remedy in France and Germany.Many studies have suggested that as a potent free radical scavenger and antagonist of platelet-activating factor (PAF) Gingko Biloba extract could ameliorate ischemia- reperfusion injury and provide protection in I/R injury of many organs such as brain, heart, liver and eyes etc .Through years of development lung transplantation has been accepted as the only effective therapy for patients with end-stage pulmonary diseases .But its successful application is still limited by donor shortage and suboptimal lung preservation technique. Therefore, optimal allograft protection is essential to reduce the organ dysfunction, especially in the early post-operative period. Ischemia-reperfusion injury is the main factor .This study is designed to explore the possible protective effect of the standardized extract of Ginkgo biloba (EGb761, Dr. Willmar Schwabe Gmbh flavonoid glycosides:3.5mg/ml;terpene:0.21mg/ml;Ginkgolic acid<5ppm) on lung ischemia-reperfusion injury following lung preservation in lung transplantation.Methods:Eighteen New Zealand white rabbits were randomly divided into three groups,which are referred to as I/R group,LPD group and E+L group(n=6 in each group).All rabbits were ventilated with the assistance of a manual mechanical ventilator at 30 breaths/min and 10 ml/kg tidal volume. In situ pulmonary I/R after flushing model was established. Lung protection solution was supplied to the left pulmonary artery via a 22G catheter, which was inserted through main pulmonary artery to the left branch. After applying the perfusion solution, ischemia was carried out for 120 min. At the end of this period, reperfusion was carried out for 90 min. In I/R group, pulmonary perfusion solution was not employed, whereas in LPD group LPD solution was employed, and in E+L group Egb761 (3.5mg/ml) was administered intravenously at doses of 20mg/kg before ischemia additionally. Blood gas analysis(PaO2),serum TNF-α level were measured before ischemia and at the 15th(30th) min,60th min,90th min of reperfusion .Lung tissue samples were obtained at theend of reperfusion. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in tissue and the dry/wet(D/W) ratio were determined. Morphological examinations were also performed.Results:(l)PaO2 :PaO2 significantly decreased after reperfusion in all groups. The I/R group showed the significantly lowest levels of oxygenation at the 15*, 60th and 90th minutes of reperfusion (122.50±20.71 ^ 64.50±5.65 and 100.00±8.58 mmHg) in comparison to the LPD (225.67±35.38, 227.67±65.73 and 240.67±41.87 mmHg) and E+L (212.17±53.85 ^ 240.50±52.48 and 236.50±51.06 mmHg) groups (?<0.01), while there were no difference between the LPD and E+L groups. (2)The TNF-a concentration in plasma: TNF-a level significantly increased after reperfusion in the three groups (.P<0.01).The E+L group displayed the lowest levels of TNF-a at the 30th ^ 60th and 90th minutes of reperfusion(48.61±6.5k 53.02±6.16and56.45±6.33 pg/ml) in comparison to the I/R (72.47±3.69^ 98.45±2.81 and 103.67±4.40pg/ml) and LPD (60.62±7.82^ 86.90±3.45 and 90.17±2.37pg/ml) groups (P<0.01).(3)MDA levels and MPO activities in lung tissue: MDA and MPO were significantly lower in the E+L group (6.59±0.73 nmol/mg and 10.38±1.07U/g ) when compared to the LPD (9.93±0.86 nmol/mg and 12.81±1.04U/g) and I/R (12.44±1.10 nmol /mg and 14.85±1.40U/g) groups (PO.01). (4)The ratio of D/W: The D/W was significantly higher in the E+L group (0.1775±0.0073) compared with the I/R group (0.1309±0.0012,i><0.01) or the LPD group(0.1550±0.0096rP<0.01).(5)Histological evaluation: Morphological examinations revealed pathological lesions at different levels in three groups .There was marked pulmonary capillary congestion, interstitial edema and intraalveolar hemorrhage, infiltration in the I/R group while E+L showed the lightest pathologic change.Conclusions:1) The production and release of oxygen free radicals and cytokines may play an important role in the lung ischemia reperfusion injury.2) Pretreatment of the donor with Egb761 could provide obvious protection against the I/R injury of the donor lung. Egb761 may decrease the formation of oxygen free radicals, inhibit aggregation and activation of neutrophils, suppress cytokines releasing.3) LPDS as lung preservation solution could ameliorate reperfusion injury of the lung.4) In situ pulmonary I/R after flushing mode] is close to the clinical operation and could be established with no difficulty. It is worth being adopted in similar researches.
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