羟乙基淀粉加多聚人胎盘血红蛋白对失血性休克大鼠肠缺血再灌注损伤的影响

Effects of addition of hydroxyethyl starch to polymerized human placenta hemoglobin during intestinal ischemia and reperfusion injury in a rat model with hemorrhagic shock

目的探讨应用羟乙基淀粉(HES)溶液中添加多聚人胎盘血红蛋白(Poly Hb)对重度失血性休克大鼠模型肠缺血再灌注的影响。方法将32只SD大鼠失血至全身血容量(大鼠体重的6.5%)的60%,分别将大鼠股动静脉插管后,从股动脉端开始放血直至放血量达到大鼠全身血容量的60%,然后随机均分为4组(8只/组),包括3个人工胶体液组,即HES组:6%HES130/0.4氯化钠注射液;红细胞+HES(RBC+HES)组:将大鼠自身血液反复离心洗涤3次,留取红细胞,加入到HES溶液中,使Hb浓度达到20 g/L;Poly Hb+HES组:将Poly PHb加入到HES溶液中,使Hb浓度为20 g/L;1个假手术组:只做常规手术,不放血不复苏。将大鼠行等容量液体复苏,分别在各组大鼠休克前、后,输液末、输液后1 h、2 h观测大鼠平均动脉压(MAP)、乳酸(Lac)、氧分压(Pa O2)、二氧化碳分压(Pa CO2),并在复苏2 h取各组大鼠肠组织制备成10%组织匀浆,测定丙二醛(MDA)、髓过氧化物酶(MPO)、肿瘤坏死因子(TNF-α)的含量。结果 HES、RBC+HES和Poly Hb+HES 3组大鼠输液后MAP(mm Hg)分别为88.00±9.90 vs 100.57±7.69vs 112.16±17.05(P"0.05);输液后2 h,乳酸(mmol/L)分别为3.71±0.91 vs 2.30±0.97 vs 2.50±0.65(P"0.05),Pa O2(mm Hg)分别为126.5±10.40 vs 111.16±9.64 vs 111.00±13.98(P"0.05),Pa CO2(mm Hg)分别为30.00±3.16 vs 42.66±5.31 vs 34.66±1.50(P"0.05);输液后2 h,RBC+HES、HES组MDA、MPO活性,分别为:0.47±0.34 vs 0.99±0.81,0.23±0.29 vs 0.57±0.32(P"0.05);Poly Hb+HES与HES组MPO活性、TNF-α分别为0.32±0.19 vs 0.57±0.32,89.42±21.03 vs 208.45±62.80(P"0.05)。结论 HES溶液添加多Poly Hb可以改善失血性休克大鼠组织氧供和酸中毒现象,减轻肠组织缺血再灌注损伤。

Objective To investigate the effect of adding hydroxyethyl starch to polymerized human placenta hemoglobin during intestinal injury in a rat model with severe hemorrhagic shock. Methods 32 rats subjected to severe hemorrhage （60% loss of the total blood volume） were randomly divided into hydroxyethyl starch （HES） group： 6% HES130/0.4 NaCl solutions; red blood ceil （RBC＋HES） group （the RBC of rats were added into 6%HES130/0.4 solutions until the concentration of hemoglobin was 20 g/L） ; the polymerized human placenta hemoglobin （PolyHb＋HES） group （PolyPHb was added into 6%HES130/0.4 solutions until the concentration of hemoglobin was 20 g/L）; control group underwent all instrument procedures without blood withdrawal and resuscitation. The volume of resuscitative fluid was identical to the removal of blood volume （ 60% of BV）. The mean arterial pressure （MAP） and blood gas were measured at baseline, shock, the end of the resuscitation and 2h after the resuscitation respectively. At the end of the study, intestinal tissue was excised to prepare 10% tissue homogenates, and the concentration of MDA, MPO, TNF-α were measured. Results The MAP （mmHg） of HES group, RBC group and PolyHb＋HES group were： 88. 00 ± 9. 90 vs 100. 57 ± 7.69 vs 112. 16 ＋ 17.05 （P〈0. 05）. At 2h ＇after resuscitation, the Lac of HES group, RBC＋HES group and PolyHb＋HES group were： 3.71 ± 0. 91 vs 2. 30 ± 0. 97 vs 2.50 ±0. 65 （P〈0. 05） ; the PaO2 were： 126. 5 ± 10. 40 vs 111.16 ± 9.64 vs 111.00 ± 13.98 （P〈0. 05） ; PaCO2 were increased： 30. 00 ± 3.16 vs 42. 66 ± 5.31 vs 34. 66± 1.50 （P 〈0. 05） , respectively. The concentration of MDA and MPO in RBC＋HES group and HES group were ： 0. 47 ± 0. 34 vs 0. 99 ± 0.81, 0.23 ± 0.29 vs 0.57 ± 0.32 （P〈0.05）. The levels of TNF-α and MPO in PolyHb＋HES and HES group were： 0. 32 ＋ 0. 19 vs 0. 57 ± 0. 32（P〈0. 05）, 89.42 ± 21.03 vs 208.45 ± 62. 80 （P〈0.05）. Conclusion The addition of hydroxyethyl starch to PolypHb could improve tissue oxygenation and acidosis, and attenuate the ischemia reperfusion injury of intestinal tissue in a rat model with hemorrhagic shock.