肺缺血-再灌注损伤时HO-1/CO系统的变化及葛根素对其的影响

目的：探讨兔肺缺血-再灌注损伤时血红素加氧酶－1（HO-1）/一氧化碳（CO）的变化及葛根素对其的影响。方法:复制在体兔原位单肺缺血－再灌注模型，随机分：假手术对照（control）组、肺缺血－再灌注（I-R）组与肺缺血－再灌注加葛根素（puerarin）组，每组10只。各组在缺血前、缺血1h、再灌注1 h、3 h和5 h分别抽血，检测一氧化碳血红蛋白(COHb)浓度、环磷酸鸟苷(cGMP)含量。实验结束时取肺组织检测湿干重比(W/D)、 肺泡损伤率(IAR)，观察肺组织超微结构的改变、HO-1的活力、表达部位及强度。结果:血浆COHb浓度、cGMP 含量I-R组、puerarin组明显高于control组，以puerarin组为著（P<0.01）。肺组织HO-1活性，I-R组较control组明显增加，puerarin组增加更加显著（P<0.01）。I-R组、puerarin组HO-1在肺血管内皮、部分血管平滑肌、外膜层及部分气道上皮呈阳性表达，明显高于control组，尤以puerarin组最为明显（P<0.01）。W/D、IAR，I-R组明显高于control组（P<0.01），puerarin组虽较control组为高，但显著低于I-R组（P< 0.01）。I-R组有明显的肺超微结构损伤，而puerarin组损伤较轻。结论:葛根素可通过上调HO-1表达，增加HO-1活性，对缺血再灌注肺发挥明显的保护作用。

Effects of puerarin on heme oxygenase-1/carbon monoxide system in lung ischemia-reperfusion injury

AIM:To investigate the variations of heme oxygenase-1/carbon monoxide system in lung ischemia-reperfusion injury and effects of puerarin on the system.METHODS:The unilateral lung ischemia-reperfusion model was replicated in vivo. Rabbits were randomly divided into three groups (n=10 in each): control group, ischemia-reperfusion (I-R) group and puerarin group. The blood specimens collected at times before ischemia, ischemia 1 h, reperfusion 1 h, 3 h and 5 h were tested for the contents of carboxyhemoglobin (COHb) and cyclic guanosine monophosphate (cGMP). The lung tissues sampled at 5 h after reperfusion were assayed for wet/dry weight ratio (W/T), the injured alveoli rate (IAR) and the activity of HO-1. The changes of ultrastructure were observed under electron microscope. The tissue slides were also stained by immunohistochemistry (IHC) and in situ hybridization (ISH) to detect the expression of HO-1.RESULTS:The plasma content of COHb and cGMP in I-R and puerarin group increased in a time-dependent manner after I-R compared with control group, but the increment in puerarin group was higher than that in I-R group (P<0.01). The activity of HO-1 was much higher in I-R group than that in control group, and the indexes in puerarin group increased more significantly (P<0.01). Expression of HO-1 was up-regulated in I-R and puerarin group than that in control group in the pulmonary vascular endothelial cells, part of pulmonary vascular smooth muscle cells, extima of vessels and epithelial cells of airway. The highest average optical density value was observed in puerarin group (P<0.01 or P<0.05). Serious ultrastructural morphological damages were observed in I-R group under electron microscope, only slightly injury was found in puerarin group.CONCLUSION:Puerarin up-regulates the expression of HO-1, improves the activity of HO-1, provides significant protective effects on lung during ischemia-reperfusion injury.