钙拮抗剂对大鼠腹部皮瓣抗氧化作用的研究

Objective　To observe the protective effect of calcium antagonist on the ischemia - reperfusion injury in rat abdominal skin flap.Methods　33 SD rats were randomized into three groups. The abdominal island flap based on the inferior epigastric vessels was used as the ischemia - reperfusion model. In the control group, normal saline was given intraperitoneally for 3 consecutive days preoperatively, while Verapamil (Ver) and Tetrandcin (Tet) were given in the other two groups respectively. Samples from the flap were harvested during ischemia and reperfusion periods to measure the changes of superoxide dismutase （SOD） activity,glutathione peroxidase （GSH - Px） activity and malonyl dialdehyde （MDA） content. Results　SOD activity and GSH - Px activity were much higher in the Ver and Tet groups than in the control group, while the MDA content was remarkably decreased in these two groups.Conclusions　Calcium antagonist, Verapamil and Tetrandcin, plays an important role in oxygen free radical scavenging and in reducing lipid peroxidation.     

Effect of superoxide dismutase for improvement of survival of ischemic reperfused island skin flap]

Using a rat model, we evaluated the effect of SOD on the survival of ischemic reperfused island skin flaps. In experiment 1, the oxygen free radical concentration in the flaps was measured by the technique of ESR. The results showed that the oxygen free radical concentration in ischemic reperfused flaps was significantly higher than in the corresponding control flaps (P less than 0.001). In experiment 2, the flaps were perfused with SOD (2000 U in 1 ml saline) before reperfusion after 8 hours of ischemia. Seven days after operation, the area of flap survived in the test group was significantly larger than in the control group (P less than 0.0005). The obtained data demonstrated that the generation of oxygen free radical increases with time during ischemia reperfusion in island skin flap and the role of oxygen free radical in tissue injury following ischemia and reperfusion. The use of SOD can enhance the survival of ischemic island skin flap.     

Prevention of reperfusion injury of an ischemic flap: an experimental study]

Oxygen-derived free radicals are important mediators of tissue injury in experimental island skin flaps that have been subjected to prolonged ischemia (vascular occlusion) followed by reperfusion. In this study, the role of oxygen free radical scavenger, SOD, and a herb, salvia miltiorrhiza, in the protection of cellular damages during total ischemia and reperfusion was study in the epigastric island skin flaps in experimental rats with electron microscopy and the assessment of survival of the flaps. Control flaps subjected to 10 hours of total vascular occlusion showed a high incidence of necrosis when followed for 7 days following release of the vascular occlusion. Treatment with superoxide dismutase and salvia miltiorrhiza prior to the onset of reperfusion significantly enhanced island flap survival to 72.5% (P < 0.001) and to 64.2% (P < 0.05), respectively. The conclusions are: 1. Reperfusion for 10 hours following ischemia for 8 hours in the epigastric island flaps of the rats greatly exaggerated the original injury. 2. SOD and salvia miltiorrhiza may protect the flaps from such injury considerably and enhanced flap survival.     

阻断CD18介导的白细胞粘附对岛状皮瓣成活的影响

研究白细胞白细胞粘附在缺血再灌注损伤中的作用。方法，应用大鼠腹部岛状皮瓣模型，检测了皮瓣过氧化酶和丙二醛含量，观察了皮瓣的成活情况。结论ＣＤ１８介导 白细胞粘附参与了皮瓣再灌注损伤过程，抗ＣＤ１８单抗阻断白细胞附能减轻白细胞介导的组织损伤，并对岛状皮瓣具有保护作用。     

Improved survival in free skin flap transfers in rats

We have demonstrated previously that oxygen-derived free radicals are important mediators of tissue injury in experimental island skin flaps that have been subjected to prolonged ischemia (vascular occlusion) followed by reperfusion. In this study the role of oxygen free radicals in ischemia/reperfusion injury has been investigated in free flap transfers. Groin skin flaps were harvested, stored at room temperature for 21 to 24 hours, and transplanted to the contralateral groin. These free flap transfers normally exhibit a high incidence of complete necrosis. Treatment before the onset of reperfusion with a single dose of superoxide dismutase (SOD), a scavenger of superoxide radicals, increased the survival rate of these skin flaps from 38% in the control group to 76% (p less than 0.025). Tissue levels of SOD were measured before ischemia, after ischemia but before reperfusion, and 30 minutes after reperfusion: untreated flap tissues, which were destined to undergo necrosis, exhibited a significant decrease in SOD activity after reperfusion, whereas SOD-treated flap tissues, destined to survive, demonstrated increased enzyme activity. High levels of tissue SOD activity thus appeared to be associated with improved flap survival. The results have significant clinical implications with regard to organ preservation and transplantation.     

阻断CD18介导的白细胞粘附对岛状皮瓣成活的影响

目的研究白细胞及白细胞粘附在缺血再灌注损伤中的作用。方法应用大鼠腹部岛状皮瓣模型，检测了皮瓣髓过氧化酶（ＭＰＯ）和丙二醛（ＭＤＡ）含量，观察了皮瓣的成活情况。结果与正常时相比，缺血８小时及再灌注１小时皮瓣ＭＰＯ和ＭＤＡ水平明显增高，而以抗ＣＤ１８单抗阻断白细胞粘附可明显减轻这种变化，并有效地提高皮瓣的存活面积。结论ＣＤ１８介导的白细胞粘附参与了皮瓣再灌注损伤过程，抗ＣＤ１８单抗阻断白细胞粘附能减轻白细胞介导的组织损伤，并对岛状皮瓣具有保护作用。     

Protective effects of vitamins A and E pretreatment in venous ischemia/reperfusion injury

It has been suggested that venous ischemia is more injurious to tissue viability than is arterial ischemia of equivalent duration. The precise mechanism of tissue damage due to venous ischemia is still not well-determined. Current research has shown that it is multifactorial, and that lipid peroxides, prostanoid metabolism, and a free radical mechanism are the major contributors. Vitamins A and E are lipid-soluble vitamins that have been suggested to be successful in the treatment of arterial ischemia/reperfusion injury due to their antioxidant properties. In the present study, the authors examined the protective effects of vitamins A and E pretreatment on reperfusion injury induced by venous occlusion of rat epigastric island flaps based on an epigastric artery and vein pedicle. In the first part of the study, to determine critical ischemia time, epigastric island skin flaps (3 x 6 cm) were elevated on their vascular pedicles in 40 male Sprague Dawley rats. Total venous occlusion of the skin flap was produced by ligating all draining veins and clamping the epigastric vein. Arterial inflow was left intact. Rats were randomly assigned to five groups (n=8) for 2, 5, 7, 9, and 10 hr of venous ischemia. Despite the occurrence of widespread reperfusion injury, reflow was established (p<0.005) at 9 hr. In the second part of the study, 20 rats were randomly divided into four groups (n=5). The effects of vitamins A and E following 9 hr ischemia/reperfusion injury were examined. Rats were pretreated with vitamin E, vitamin A and vitamins A+E for 5 days. At the end of the fifth day, each rat had undergone an epigastric island skin flap and venous occlusion, as described above. Mean surviving flap area (percent) and plasma lipid peroxides (TBARs), total thiol content (t-SH), glutathione peroxidase (Gpx), and superoxide dismutase (SOD) were determined for each rat. Results suggest that, in the prevention of venous ischemia/reperfusion injury, vitamin A and vitamin E are not effective when used as single agents; however, when used in combination, they significantly increase surviving flap area by a synergistic effect.     

阻断CD_(18)介导的白细胞粘附对岛状皮瓣成活的影响

目的研究白细胞及白细胞粘附在缺血再灌注损伤中的作用。方法应用大鼠腹部岛状皮瓣模型,检测了皮瓣髓过氰化酶(MPO)和丙二醛(MDA)含量,观察了皮瓣的成活情况。结果与正常时相比,缺血8小时及再灌注1小时皮瓣 MPO 和 MDA 水平明显增高,而以抗 CD_(18)单抗阴断白细胞粘附可明显减轻这种变化,并有效地提高皮瓣的存活面积。结论 CD_(18)介导的白细胞粘附参与了皮瓣再灌注损伤过程,抗 CD_(18)单抗阻断白细胞粘附能减轻白细胞介导的组织损伤,并对岛状皮瓣具有保护作用。     

Effect of scavengers of superoxide radicals in reducing ischemic injury of skin flaps

In recent years, an extensive attention has been paid to the effects of oxygen free radicals on tissue injury. Although some studies have been demonstrated that the oxygen free radicals are implicated in the pathogenesis of ischemic injury in island skin flaps, none of the experimental study has been domestically reported. The authors used the island flap of the rats as an animal model to investigate the effectiveness of free radical scavengers in preventing reperfusion injury after ischemia in island skin flap. The results suggest that the scavenger of superoxide radical--superoxide dismutase (SOD) which was directly injected into the flap before and after reperfusion increases the survival rate of the flap obviously (93.6% v.s. control 63.7%). This findings are consistent with the theory that the ischemic tissue injury is caused by the oxygen free radicals produced at the time of tissue reperfusion.     

Protective effects of pretreatment with Radix Paeoniae Rubra on acute lung injury induced by intestinal ischemia/reperfusion in rats

Objective： To investigate the effect of pretreatment with Radix Paeoniae Rubra （RPR） on acute lung injury induced by intestinal ischemia/reperfusion in rats and its protective mechanism.
Methods： Thirty-two Wistar rats were randomly divided into four groups： Sham-operation group, ischemla/ reperfusion group （I/R group ）, RPR-pretreatment group and hemin group. The model of intestinal ischemia/ reperfusion was established by clamping the superior mesenteric artery for 1 hour followed by 2-hour reperfusion. The effect of RPR on the expression of heme oxygenase-1 （HO-1） in lung tissues was detected by immunohistochemistry and morphometry computer image analysis. Arterial blood gas analysis, lung permeability index, malondialdehyde （MDA） and superoxide dismutase （SOD） contents in lungs were measured. The histological changes of lung tissue were observed under light microscope.
Resalts： The expression of HO-1 in RPR-pretreatment group and hemin group was obviously higher than that in sham-operation group and I/R group （ P 〈 0.01 ）. The level of MDA and lung permeability index in RPR-pretreatment and hemin group were significantly lower than those in I/R group （P〈0.01 or P〈0.05）, while the activity of SOD in RPR-pretreatment and hemin group was obviously higher than that in I/R group （P〈0.01）. Under light microscope, the pathologic changes induced by I/R were significantly attenuated by RPR.
Conclusion： Intestinal ischemia/reperfusion may result in acute lung injury and pretreatment with RPR injection can attenuate the injury. The protective effect of RPR on the acute lung injury is related to its property of inducing HO-1 expression and inhibiting lipid peroxidation.