Lieberthal W, Fuhro R, Andry C, Valeri C R
Renal and Pathology Divisions, and the Naval Blood Research Laboratory, Boston University Medical Center, Massachusetts, USA.
J Lab Clin Med. 2000 Jan;135(1):73-81. doi: 10.1016/s0022-2143(00)70023-0.
The effects of three hemoglobin solutions were compared with those of iso-oncotic human serum albumin in rats with ischemic renal failure and sham-operated controls. Unmodified and alpha-alpha cross-linked hemoglobins both increase mean arterial pressure and systemic vascular resistance and reduce cardiac output substantially and to a comparable extent. In contrast, omicron-raffinose cross-linked hemoglobin has no deleterious effect on any of these parameters. In sham-operated rats unmodified hemoglobin reduces the glomerular filtration rate (GFR) by approximately 30%, whereas neither of the two cross-linked hemoglobins has any adverse effect on GFR in this group. None of the three hemoglobin solutions exacerbated the degree to which GFR was reduced by ischemia-reperfusion injury. Also, the degree of tubular necrosis induced by ischemia-reperfusion injury was also comparable in all groups. We conclude the following: (1) omicron-raffinose cross-linking, but not alpha-alpha cross-linking, ameliorates the effects of unmodified hemoglobin on vascular resistance and cardiac output; (2) both forms of cross-linking reduce the nephrotoxicity exhibited by unmodified hemoglobin in sham-operated rats; and (3) none of the hemoglobin solutions exacerbate renal injury induced by ischemia-reperfusion.
在缺血性肾衰竭大鼠和假手术对照组中,比较了三种血红蛋白溶液与等渗人血清白蛋白的效果。未修饰的血红蛋白和α-α交联血红蛋白均会升高平均动脉压和全身血管阻力,并大幅降低心输出量,且降低程度相当。相比之下,O-棉子糖交联血红蛋白对这些参数均无有害影响。在假手术大鼠中,未修饰的血红蛋白使肾小球滤过率(GFR)降低约30%,而两种交联血红蛋白在该组中对GFR均无不良影响。三种血红蛋白溶液均未加剧缺血再灌注损伤导致的GFR降低程度。此外,缺血再灌注损伤诱导的肾小管坏死程度在所有组中也相当。我们得出以下结论:(1)O-棉子糖交联而非α-α交联可改善未修饰血红蛋白对血管阻力和心输出量的影响;(2)两种交联形式均降低了未修饰血红蛋白在假手术大鼠中表现出的肾毒性;(3)所有血红蛋白溶液均未加剧缺血再灌注诱导的肾损伤。