戊二醛聚合猪血红蛋白在术中急性贫血状态下有效性研究
发布时间：2018-11-19 11:45
【摘要】：贫血是临床最常见的表现之一,症状的轻重与贫血发生的程度及进展速度有关,急性重度贫血可导致组织缺氧性损伤甚至死亡,输入血液或血液制品是临床治疗急性贫血的主要方法。但由于血液感染风险、血液短缺、血液误输以及保存方式等因素,寻求合适的血液替代品成为必然趋势。血红蛋白氧载体(Hemoglobin-based oxygen carriers,HBOCs)是以血红蛋白为基础的一类能够代替血液部分功能的化合物。戊二醛聚合猪血红蛋白(polymerized porcine hemoglobin, pPolyHb)是由戊二醛交联聚合猪血红蛋白制备的一种新型的HBOCs,其前期在失血性休克、100%换血等动物模型中,从血流动力学,酸碱代谢,氧供等多方面证明该产品具有良好的扩容及携氧释氧能力,可以保证实验动物正常组织灌注及血流动力学稳定,可有效替代红细胞发挥作用。本实验通过探讨pPolyHb在大鼠和犬急性贫血模型中的复苏效果及其对肝肾等组织的影响进一步证明pPolyHb的有效性。首先探讨pPolyHb在大鼠急性贫血/治疗中对机体血压及动脉血气指标、肝肾损伤因子以及不同液体复苏组织病理损伤情况。建立大鼠等容血液稀释模型,将大鼠血红蛋白含量稀释至4±0.5g/dl或5±0.5g/dl,模拟临床术中贫血,稀释后,通过静脉以0.3mL/min速率输入pPolyHb或红细胞(RBC),至血红蛋白含量大于7g/dl,control组不进行复苏;监控血压和动脉血气指标,术后7d检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸转移酶(AST)等肝肾损伤因子含量,处死解剖后通过肾组织HE染色检测病理变化;pPolyHb组和RBC组复苏后血压能够恢复到基础水平,同对照组相比,复苏后pPolyHb组无氧代谢得到显著性改善,有效的纠正了组织酸中毒现象,与红细胞组复苏效果类似,pPolyHb组肝肾损伤因子及肾脏病理组织HE染色结果与sham组没有显著性差异,并优于红细胞组;以上结果表明pPolyHb可以改善大鼠血流动力学参数,减轻代谢性酸中毒,并且可以降低肝肾损伤因子的活性,其治疗效果与RBC相当,显著地优于control组。在犬等容血液稀释模型中,用同样的方法模拟急性贫血状态,研究RBC不可获得的情况下pPolyHb的作用效果。血液稀释后犬随机分为两组,实验组输入3g/kg pPolyHb,对照组以肺动脉楔压(PAWP)为参照,输入生理盐水;监测实验过程中血流动力学参数、血气指标、氧供氧耗参数和凝血状态,术后7d检测血清中肝肾损伤因子含量,解剖后观察肝、肾组织HE染色结果;pPolyHb在无RBC制品情况下使用对血流动力学稳定的维持较晶体液有一定优势,对组织的氧供有一定改善,并且可以降低肝肾损伤因子的活性,在7天后未造成明显特异性的组织损伤。实验表明pPolyHb能够显著的改善犬由于等容血液稀释引起的急性贫血状态。
[Abstract]:Anemia is one of the most common clinical manifestations. The severity of symptoms is related to the degree of anemia and the rate of progression. Acute severe anemia can lead to tissue hypoxia injury or even death. Transfusion of blood or blood products is the main clinical treatment of acute anemia. However, due to the risk of blood infection, blood shortage, blood miscarriage and preservation, it is an inevitable trend to seek suitable blood substitutes. Hemoglobin oxygen carrier (Hemoglobin-based oxygen carriers,HBOCs) is a kind of hemoglobin-based compounds which can replace the partial function of blood. Glutaraldehyde polymerized porcine hemoglobin (polymerized porcine hemoglobin, pPolyHb) is a new type of HBOCs, prepared from glutaraldehyde crosslinked polymerized porcine hemoglobin. Oxygen supply and other aspects have proved that the product has a good capacity to expand and carry oxygen, which can ensure the normal tissue perfusion and hemodynamic stability of experimental animals, and can effectively replace the role of red blood cells. The effect of pPolyHb on liver and kidney tissues in acute anemia model of rats and dogs was studied to further prove the effectiveness of pPolyHb. To investigate the effects of pPolyHb on blood pressure, arterial blood gas, liver and kidney injury factors and pathological injury of different fluid resuscitation tissues in acute anemia / treatment of rats. An isovolumetric hemodilution model was established in rats. The hemoglobin content was diluted to 4 卤0.5g/dl or 5 卤0.5 g / dl. after hemodilution, the hemoglobin content was injected into pPolyHb or erythrocyte (RBC), via vein at 0.3mL/min rate. When the hemoglobin content was more than 7 g / dll control group, no resuscitation was carried out. Blood pressure and arterial blood gas were monitored. Serum alanine aminotransferase (ALT), aspartate transferase (AST) and other liver and kidney injury factors were detected 7 days after operation. Pathological changes were detected by HE staining in renal tissue after death. The blood pressure of pPolyHb group and RBC group could recover to the basic level after resuscitation. Compared with the control group, the anaerobic metabolism in pPolyHb group was significantly improved after resuscitation, which effectively corrected the phenomenon of tissue acidosis, which was similar to that in the erythrocyte group. There was no significant difference in liver and kidney injury factor and HE staining between pPolyHb group and sham group, and it was superior to erythrocyte group. These results suggest that pPolyHb can improve hemodynamic parameters, alleviate metabolic acidosis and decrease the activity of liver and kidney injury factors in rats. The therapeutic effect of pPolyHb is similar to that of RBC and is significantly better than that of control group. In canine isovolumetric hemodilution model, the same method was used to simulate the acute anemia and to study the effect of pPolyHb on the condition that RBC was not available. The dogs were randomly divided into two groups after hemodilution. The experimental group was given 3g/kg pPolyHb, as the control group and the pulmonary artery wedge pressure (PAWP) as the reference. The hemodynamic parameters, blood gas index, oxygen supply oxygen consumption parameter and coagulation state were monitored. The serum levels of liver and kidney injury factors were measured 7 days after operation. The results of HE staining in liver and kidney tissues were observed after dissection. In the absence of RBC products, pPolyHb has some advantages over crystal liquid in maintaining hemodynamic stability, improving the oxygen supply of tissues, and reducing the activity of liver and kidney injury factors. No specific tissue damage was caused after 7 days. Experimental results show that pPolyHb can significantly improve the acute anemia caused by isovolumetric hemodilution in dogs.
【学位授予单位】：西北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R556
本文编号：2342218
[Abstract]:Anemia is one of the most common clinical manifestations. The severity of symptoms is related to the degree of anemia and the rate of progression. Acute severe anemia can lead to tissue hypoxia injury or even death. Transfusion of blood or blood products is the main clinical treatment of acute anemia. However, due to the risk of blood infection, blood shortage, blood miscarriage and preservation, it is an inevitable trend to seek suitable blood substitutes. Hemoglobin oxygen carrier (Hemoglobin-based oxygen carriers,HBOCs) is a kind of hemoglobin-based compounds which can replace the partial function of blood. Glutaraldehyde polymerized porcine hemoglobin (polymerized porcine hemoglobin, pPolyHb) is a new type of HBOCs, prepared from glutaraldehyde crosslinked polymerized porcine hemoglobin. Oxygen supply and other aspects have proved that the product has a good capacity to expand and carry oxygen, which can ensure the normal tissue perfusion and hemodynamic stability of experimental animals, and can effectively replace the role of red blood cells. The effect of pPolyHb on liver and kidney tissues in acute anemia model of rats and dogs was studied to further prove the effectiveness of pPolyHb. To investigate the effects of pPolyHb on blood pressure, arterial blood gas, liver and kidney injury factors and pathological injury of different fluid resuscitation tissues in acute anemia / treatment of rats. An isovolumetric hemodilution model was established in rats. The hemoglobin content was diluted to 4 卤0.5g/dl or 5 卤0.5 g / dl. after hemodilution, the hemoglobin content was injected into pPolyHb or erythrocyte (RBC), via vein at 0.3mL/min rate. When the hemoglobin content was more than 7 g / dll control group, no resuscitation was carried out. Blood pressure and arterial blood gas were monitored. Serum alanine aminotransferase (ALT), aspartate transferase (AST) and other liver and kidney injury factors were detected 7 days after operation. Pathological changes were detected by HE staining in renal tissue after death. The blood pressure of pPolyHb group and RBC group could recover to the basic level after resuscitation. Compared with the control group, the anaerobic metabolism in pPolyHb group was significantly improved after resuscitation, which effectively corrected the phenomenon of tissue acidosis, which was similar to that in the erythrocyte group. There was no significant difference in liver and kidney injury factor and HE staining between pPolyHb group and sham group, and it was superior to erythrocyte group. These results suggest that pPolyHb can improve hemodynamic parameters, alleviate metabolic acidosis and decrease the activity of liver and kidney injury factors in rats. The therapeutic effect of pPolyHb is similar to that of RBC and is significantly better than that of control group. In canine isovolumetric hemodilution model, the same method was used to simulate the acute anemia and to study the effect of pPolyHb on the condition that RBC was not available. The dogs were randomly divided into two groups after hemodilution. The experimental group was given 3g/kg pPolyHb, as the control group and the pulmonary artery wedge pressure (PAWP) as the reference. The hemodynamic parameters, blood gas index, oxygen supply oxygen consumption parameter and coagulation state were monitored. The serum levels of liver and kidney injury factors were measured 7 days after operation. The results of HE staining in liver and kidney tissues were observed after dissection. In the absence of RBC products, pPolyHb has some advantages over crystal liquid in maintaining hemodynamic stability, improving the oxygen supply of tissues, and reducing the activity of liver and kidney injury factors. No specific tissue damage was caused after 7 days. Experimental results show that pPolyHb can significantly improve the acute anemia caused by isovolumetric hemodilution in dogs.
【学位授予单位】：西北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R556
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相关期刊论文 前2条
1 李军;倪燕秀;张继娟;吴梧桐;;聚乙二醇修饰猪血红蛋白的抗原性研究[J];中国药学杂志;2008年02期
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，本文编号：2342218
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