| Hemoglobin-based oxygen carriers (HBOCs), one category of blood substitute, are synthesized from chemically modified human or bovine hemoglobin. HBOCs have similar function with red blood cell and are mainly used in the treatment of trauma and hemorrhagic shock. However, the effect of HBOCs on ischemia reperfusion injury is rarely investigated. Increasing oxygen transport is the main reason inducing ischemia reperfusion injury, because it can induce more superoxide anion free radicals and exacerbate tissue oxidation, resulting in cell death or apoptosis. Polymerized porcine hemoglobin (pPolyHb) can carry and release oxygen and its diameter is small enough to pass through the obstruction to provide oxygen and nutrient for the ischemic area. In this paper, we explore pPolyHb protective effect on cerebral ischemia reperfusion injury in vitro and in vivo.Cell model of oxygen and glucose deprivation (OGD) was prepared to simulate ischemia reperfusion injury, and the restoration effect of pPolyHb was estimated via detecting cell survival rate and activity of superoxide dimutase. Rat model of focal cerebral ischemia reperfusion was induced by middle cerebral artery occlusion method. After 90min ischemic stage, the nylon thread was withdrawn and reperfusion injury was induced. Once ischemia, 0.5g/Kg pPolyHb was injected via caudal vein. Apoptosis and inflammatory cytokines were detected to evaluate the effect of pPolyHb on focal cerebral ischemia reperfusion injury.Cell experimental results showed that pPolyHb was nontoxic to HT22 cell and could repair oxidative stress injury through increased cell survival rate. Therefore, pPolyHb could repair ischemia reperfusion injury of HT22 cell. Rat ischemia reperfusion results showed that pPolyHb group not only significantly lowered the infract volume and increased neurological scores than Control group at 24 hours after reperfusion, but aslo had obviously fewer apoptosis cells and higher apoptotic protein Bcl-2/Bax ratio expression. It suggested that pPolyHb could decrease cell death rate inducing by ischemia reperfusion injury. The expression trend of inflammatory cytokine suggested that pPolyHb could reduce the expression of TNF-αⅥIL-1β and the activity of MPO, and alleviate the concentration of oxidative stress markers MDA. At the same time, the expression of anti-inflammatory factor IL-10 was enhanced. Therefore, it was concluded that pPolyHb can attenuate the inflammtory response of cerebral ischemia reperfusion injury.In conclusion, pPolyHb could carry and release oxygen whenever necessary. The diameter of pPolyHb is only 20nm which is far smaller than that of red blood cells. It can transport oxygen and nutrient through narrowed vessels to ischemia region. Moreover, pPolyHb can reduce oxidative stress injury and lower the expression of inflammatory factors, therefore pPolyHb could attenuate ischemia reperfusion injury. New approach is provided for clinical application of pPolyHb. |
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