左旋精氨酸对兔肺缺血-再灌注损伤时蛋白激酶C基因表达的影响

Effect of L-arginine on expression of PKC mRNA in pulmonary injury induced by ischemia-reperfusion in rabbits

目的探讨左旋精氨酸对肺缺血-再灌注损伤(PIRI)时蛋白激酶C基因表达的影响。方法采用在体兔单肺原位缺血-再灌注模型。实验兔27只,随机均分为假手术对照组(sham)、肺缺血-再灌注组(I-R)和肺缺血-再灌注加左旋精氨酸治疗组(L-Arg)。再灌注60 min时点取肺组织,观察蛋白激酶C (PKC)mRNA定位表达、超氧化物歧化酶(SOD)活性、丙二醛(MDA)浓度、一氧化氮(NO)含量、肺组织湿干重比(W/D)、肺损伤组织学定量评价指标(IQA)及光镜、电镜下的组织形态学改变。结果肺再灌注60 min,L-Arg组PKC mRNA在肺小动脉内膜、外膜及薄壁小血管(主要是肺小静脉)强阳性表达,其吸光度值与sham组及I-R组比较,差异有显著性(P＜0．05和P＜0．01)；SOD活性明显高于I-R组(均P＜0．01)；MDA浓度、W/D和IQA值显著低于I-R组(P＜0．01和P＜0．05)；肺组织形态学异常改变不同程度减轻。结论L-精氨酸可上调肺组织PKC-α、δ、θmRNA的表达,而提高体内NO水平、降低氧自由基水平、减轻脂质过氧化反应,对PIRI发挥积极的防护作用。

Objective To investigate the effect of L-arginine on expression of protein kinase C （PKC） mRNA during pulmonary ischemia and reperfusion injury （PIRI） in the rabbits. Methods Single lung ischemia and reperfusion animal model was used in vivo. The rabbits were randomly divided into three groups （ n = 9, in each）, sham operated group （Sham）, PIR group （I-R） and PIR＋ L-arginine group （L-Arg）. Changes of several rariables including malondialdehyde （MDA） , superoxide dismutase （SOD）, malondialde hyde （MDA）, nitril oxide （NO）, wet to dry ratio of lung tissue weight （W/D） and index of quantitative assessment （IQA） of histologic lung injury were recorded at 60 minutes after reperfusion in lung tissue. Meanwhile the location and expression of PKC mRNA were observed. Lung tissue was prepared for light microscopic and electron microscopic observation at 60 minutes after reperfusion. Results In comparison with group I-R, PKC mRNA strongly expressed in intima and extima of small pulmonary artery as well as thin-wall vessels （mostly small pulmonary veins）. The average optical density values of PKC-α、δ and θ mRNA in small pulmonary veins in L-Arg group had significance （all P 〈 0.01） ; SOD increased while MDA, W/D and IQA decreased at 60 minutes after reperfusion in lung tissue （ P 〈 0.01 and P 〈 0.05）. A morphologically abnormal changes of the lung tissue, were lessen markedly in L-Arg group. Conclusion L-arginine possess notably protective effects on PIRI in rabbits by activating PKC-α、δand θ mRNA expression in lung tissue, raising NO level, dropping oxygen free radical level and decreasing lipid peroxidation.