| 敲除诱导性一氧化氮合成酶治疗骨骼肌缺血再灌注损伤的实验研究 |
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Received:November 06, 2001
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| 期刊信息：《中国骨伤》2002年15卷，第3期，第148-151页 |
| DOI：doi:10.3969/j.issn.1003-0034.yyyy.nn.zzz |
| 基金项目:美国NIH基金 (HL360 4 6)资助 |
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目的:研究敲除诱导性一氧化氮合成酶治疗骨骼肌缺血再灌注损伤的机制和作用。
方法:本实验采用敲除一氧化氮合成酶的小鼠(治疗组)及正常小鼠(对照组)各21只,造成去神经游离提睾肌皮瓣完全缺血3小时,在荧光显微镜下,活体动态观察该肌肉在恢复血液灌注前后90分钟过程中平均微动脉管径的一系列变化,测量灌注前后肌肉的血恢复率,重量比率,并观察其病理变化。
结果:(1)在灌注后10和90分钟,对照组小鼠肌肉的再灌注率分别为(38..7±18)%和(63.8±50.3)%;而治疗组已达(92.9±17.2)%和(108.7±25.0)%(P<0.001)。(2)再灌注10分钟时,对照组的平均微动脉管径始终维持在未缺血时的515%至575%之间,90分钟后分别达到(71.6±10.9)%(10～20um),(71.2±15.1)%(21～40um),(63.4±11.2)%(41～70um)。而治疗组再灌注10分钟时的平均微动脉的管径即为缺血前的72%,90分钟以后,分别达到(91.8±7.8)%(10～20um),(88.2±7.6)%(21～40um),(85.4±6.6)%(41～70um)(P<0.001)。(3)缺血3小时再灌注90分钟后,左、右两侧提睾肌的重量比,对照组为(173.3±44.5)%,而治疗组为(116.2±7.7)%(P<0.01)。
结论:诱导型一氧化氮合成酶的敲除能有效地改善骨骼肌的缺血再灌注损伤,其作用机理可能主要是通过调节血管张力,骨骼肌的血流量,抑制白细胞粘附于内皮细胞表面从而抑制血管壁内皮下细胞增殖及调控缺血后的代谢产物。 |
| [关键词]:一氧化氮 酶诱导 再灌注损伤 |
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| NOS-2 knockout attenuates ischemia reperfusion injury in mice model |
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Abstract:
Objective:To evaluate the function of NOS-2 knockout in ischemia/reperfusion(I/R) injury
Methods:The left cremaster muscles of male mice weighting 20g were isolated and opened on the ventral side via an incision of the scrotum.Three hours of ischemia was achieved by clamping the main vascular pedicle of the isolated muscle and denervation by resecting a 3mm segment of the genitofemoral nerve.Vessel diameter changes in a selected arterial tree containing vessel sizes of 10 70um during reperfusion were measured by using an intravital microscope that connected to a recording and measuring system.Overall blood flow of the muscle was measured by using a laser Doppler flowmetry.Measurements were recorded at 10min intervals a 90min reperfusion period.Weight ratio(% of normal),pathologic features of the cremaster muscle and analysis the difference of the protein components by SDS PAGE were documented as indexes.
Results:1)At 10min of reperfusion,the mean blood flow was (38.7±18)% of baseline in the control group and (92.9±17.2)% in the NOS-2 knockout group (P<0.001).The blood flow increased to (63.8±50.3)% in the control group at 90min.In the NOS-2 knockout group,it increased to(108.7±25.0)% at 90min of reperfusion (P<0.001). 2)The average diameters of three vessel diameter categories(10-20,21-40,and 41-70um)in the controls were between 51.5% to 57.5% of baseline at 10min of reperfusion(P<0.001) and gradually increased to the maximum level of 71.6% in 10 20um,71.2% in 21-40um,63 4% in 41-70um vessles at 90min of reperfusion.In contrast,the diameter in the iNOS gene group sharply increased to 72% of baseline level at 10min of reperfusion and reached their maximum level to 91.8%,88.2%,85.4%(10-20,21-40 and 41-70um) throughout 90min of observation(P<0.001). 3)The weigh ratio of the muscles differed significantly between these two groups (P<0 001). 4)Pathology slides show that NOS-2 knockout can signifi cantly reduce inflammation and neutrophil extravasation.
Conclusion:The data from this study suggest that 1)Ischemia/reperfusion results in an increase of NOS-2 activity and/or production in the reperfused tissues. 2)iNOS gene knockout improved microcirculation in the reperfused tissue,thereby reducing reperfusion injury and improving the "no reflow"phenomenon. |
| KEYWORDS:Nitric oxide Enzyme induction Reperfusion injury |
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| 引用本文，请按以下格式著录参考文献： |
| 中文格式: | 张俐,Anthony V.Seaber,James R.Urbaniak.敲除诱导性一氧化氮合成酶治疗骨骼肌缺血再灌注损伤的实验研究[J].中国骨伤,2002,15(3):148~151 |
| 英文格式: | ZHANG Li,Anthony VSeaber.NOS-2 knockout attenuates ischemia reperfusion injury in mice model[J].zhongguo gu shang / China J Orthop Trauma ,2002,15(3):148~151 |
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