| Background and Objective: Although lung transplantation has been established as the only valid therapeutic approach for end-stage pulmonary disease, several related problems remain to be solved. In addition to the serious problem of donor shortage, primary graft dysfunction, which is mostly caused by ischemia-reperfusion injury, represents one of the most frequent causes of early mortality. As an extract of red ginseng and monkshood, Shenfu injection is a mixture mainly composed of panaxoside and Aconitum carmichaelii (AC). Pharmacological evidences suggest that panaxoside and AC can eliminate oxygen free radicals and resist lipid peroxidation. Panaxoside can provid energy groundsubstance, increase substrate level prosphorylation, promote the synthesis of adenosine triphosphate or creatine phosphate, protect the activities of calcium pump in mitochondria, diminish the degradation of mitochondrial membrane phospholipids and maintain the integrity of membrane system. Monkshood can inhibit the gathering of platelet and improve the microcirculation of ischemic tissue simultaneously. Shenfu injection has the function of lessening ischemia-reperfusion injury based on the pharmacologic action of its active components. It was confirmed in the past few years that Shenfu injection can protect many organs such as heart, brain, liver, kidney, intestines against ischemia-reperfusion injury efficiently and improve their functions notably. But no investigations were found which applied Shenfu injection to lung transplantation. In this study, we investigated whether Shenfu injection can protect against the ischemia-reperfusion injury in the donor lung during lung transplantation in a rabbit model so that we can find a new method for lung preservation.Method: Twenty rabbits, weighing 2. 0-2. 5 kg, were randomized into two groups(Group NS vs Group SF ).In situ left lung ischemia-reperfusion model was established. Group SF received Shenfu injection 2.5ml/kg i.v. at 30 minute before clamping, Shenfu injection 5ml/kg + Ringer's solution 25ml/kg were infused through the pulmonary arterial catheter which was inserted through pulmonary trunk to the sinistral branch before clamping, Shenfu injection 5ml/kg was infused again through the same channel upon reperfusion; Group NS received equivalent volumes of 0.9% Sodium Chloride instead of ShenFu injection in the same methods as contrast. The sinistral pulmonary vein blood, 2ml, in two groups was harvested at preclamping, the 15th, 30th, 60th minute after reperfusion respectively. The left lung tissue sample was obtained at 60 minute after reperfusion. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity of pulmonary vein blood, dry/wet ratio (D/W) of lung tissues were measured. Pathological changes of lung tissue were observed under microscope. Results:(1) Content of MDA- Levels of MDA in group NS and group SF at points before blockage, the 15th ,30th, 60th minutes after reperfusion were 1.2577±0.3418, 1.47344±0.3526,1.5649±0.4120,1.6465±0.6361 vs 1.2852±0.2751,1.0646±0.325%1.1353±0.3071,1.1443±0.1782 respectively. There was no significant difference in the content of MDA between group NS and group SF before clamping (P＞0.05). Compared with the level before blockage, the content of MDA in group SF decreased at the 15th minute after reperfusion .With the extension of reperfusion time, the content of MDA in both groups NS showed a tendency of increasing. But the contents of MDA in group SF were significantly lower than those in group NS (P＜0.05).(2) SOD activity: The total SOD activities in group NS and group SF at points before blockage, the 15th ,30th, 60th minute after reperfusion were 98.7033±7.9979,97.64166±16.9688,88.5113±10.2482,89.6966±5.1720 vs 109.62014±14.6034,105.28854±7.3424,105.0111±15.3270,108.26114±11.4156 respectively. The level of SOD activity in group SF before blockage was significantly higher when compared to group NS (P＜0.05), while the levels of SOD activity in two groups were decreased at the 15th,30th,60th minute after reperfusion, which was obvious in group NS. But the levels of SOD activity were significantly higher in group SF than group NS at each point of reperfusion time (P＜0.01). There was no significant difference of the total SOD activities before ischemia and after reperfusion in group SF (P＞0.05).(3) The dry/wet ratio (D/W) of lung: The D/W was significantly lower in group NS (0.19494±0.0202) compared with that in group SF (0.2298±0.0071) (P＜0.01). (4) Pathological changes of lung- Pathological examination revealed different changes in two groups. There were marked pulmonary capillary congestion, interstitial edema, abound leucocyte infiltration and lamellar exudation in group NS, while tissues in group SF showed lighter pathologic changes.Conclusions:1. It as observed that Shenfu injection could protect the donor lung efficiently against ischemia-reperfusion injury in lung transplantation in rabbit model, reducing content of MDA while increasing SOD activities. The mechanism might be based on that Shenfu injection could prohibit the development of lipid peroxidation and strengthen the ability of removing oxygen free radical.2. Shenfu injection could lessen the pulmonary edema efficiently after ischemia-reperfusion injury, which was probably because of its "multitarget effect".3. The mimic lung transplantation animal model in this research is a modified in situ pulmonary ischemia-reperfusion model, it is worth being adopted in similar researches because of its simplicity and repeatability. |
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