王春华, 岳晓, 武伟, 等. 血必净注射液减轻ECMO保存的离体空跳猪心脏的炎症反应[J]. 器官移植, 2024, 15(5): 772-779. DOI: 10.3969/j.issn.1674-7445.2024090
引用本文: 王春华, 岳晓, 武伟, 等. 血必净注射液减轻ECMO保存的离体空跳猪心脏的炎症反应[J]. 器官移植, 2024, 15(5): 772-779. DOI: 10.3969/j.issn.1674-7445.2024090
Wang Chunhua, Yue Xiao, Wu Wei, et al. Xuebijing injection alleviates inflammatory response in isolated empty beating pig hearts preserved by ECMO[J]. ORGAN TRANSPLANTATION, 2024, 15(5): 772-779. DOI: 10.3969/j.issn.1674-7445.2024090
Citation: Wang Chunhua, Yue Xiao, Wu Wei, et al. Xuebijing injection alleviates inflammatory response in isolated empty beating pig hearts preserved by ECMO[J]. ORGAN TRANSPLANTATION, 2024, 15(5): 772-779. DOI: 10.3969/j.issn.1674-7445.2024090

血必净注射液减轻ECMO保存的离体空跳猪心脏的炎症反应

Xuebijing injection alleviates inflammatory response in isolated empty beating pig hearts preserved by ECMO

  • 摘要:
    目的  探讨血必净注射液对体外膜肺氧合保存离体空跳猪心过程中炎症反应的调节作用。
    方法 12头健康广西巴马小型猪随机分为血必净组(n=6)和生理盐水组(n=6)。血必净组模型建立后,经膜式氧和器,微量泵泵注血必净注射液5 mL/h;生理盐水组则以等量的0.9%氯化钠注射液进行泵注,两组均持续泵入8 h。记录两组猪心脏的复跳时间以及8 h后灌注压、心率、灌注流量。观察保存8 h后停搏的心脏左心室壁心肌组织的病理学及超微结构改变。检测两组在模型建立初(T0)、2 h(T2)、4 h(T4)、6 h(T6)、8 h(T8)时血清中心肌损伤标志物及炎症因子水平。检测T0、T2、T4、T6、T8时刻心肌组织中NOD样受体蛋白3(NLRP3)、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)、凋亡相关斑点样蛋白(ASC)信使RNA(mRNA)的表达。
    结果 两组心脏复跳时间及保存8 h后的灌注压、心率、灌注流量比较差异均无统计学意义(均为P>0.05)。与生理盐水组比较,血必净组T4时乳酸脱氢酶(LDH),T6、T8时肌酸激酶(CK)、LDH、α-羟丁酸脱氢酶(α-HBDH)水平均较低,T4、T6、T8时肿瘤坏死因子(TNF)-α,T0、T2、T4、T6、T8时白细胞介素(IL)-6、IL-18、IL-1β水平均较低,T2、T4、T6时NLRP3、Caspase-1,T8时Caspase-1、ASC的mRNA相对表达水量较低(均为P<0.05)。苏木素-伊红染色及透射电镜结果显示血必净组心肌组织损伤程度较生理盐水组轻。
    结论 血必净注射液能有效减轻ECMO保存离体空跳猪心过程中的炎症反应,具有一定的心肌保护作用。

     

    Abstract:
    Objective  To investigate the regulatory effect of Xuebijing injection on inflammatory reaction during the preservation of isolated empty beating pig hearts with extracorporeal membrane oxygenation.
    Methods Twelve healthy Guangxi Bama miniature pigs were randomly divided into the Xuebijing group (n=6) and normal saline group (n=6). After the models were established in the Xuebijing group, Xuebijing injection was given at a dose of 5 mL/h through micropump in membrane oxygenator. In the normal saline group, an equivalent amount of 0.9% sodium chloride injection was pumped. Continuous pumping was performed for 8 h in both groups. The time of cardiac resuscitation and perfusion pressure, heart rate, perfusion flow rate after 8 h preservation were recorded in two groups. Pathological and ultrastructural changes of myocardial tissues in the left ventricular wall of hearts with cardiac arrest were observed after 8 h preservation. Serum levels of myocardial injury markers and inflammatory cytokines were detected in two groups at the beginning (T0), 2 h (T2), 4 h (T4), 6 h (T6) and 8 h (T8) after model establishment, respectively. The expression levels of NOD-like receptor protein 3(NLRP3), cysteinyl aspartate specific proteinase-1(Caspase-1), apoptosis-associated speck-like protein containing a CARD(ASC) messenger RNA (mRNA) in myocardial tissues were measured at T0, T2, T4, T6 and T8, respectively.
    Results There were no significant differences in the time of cardiac resuscitation and perfusion pressure, heart rate, perfusion flow rate after 8 h preservation between two groups (all P>0.05). Compared with the normal saline group, the levels of lactate dehydrogenase (LDH) at T4, creatine kinase (CK), LDH and α-hydroxybutyrate dehydrogenase (α-HBDH) at T6 and T8, tumor necrosis factor (TNF)-α at T4, T6 and T8, and interleukin (IL)-6, IL-18 and IL-1β at T0, T2, T4, T6 and T8 were lower, and the mRNA relative expression levels of NLRP3 and Caspase-1 at T2, T4 and T6, and Caspase-1 and ASC at T8 were lower in the Xuebijing group, respectively (all P<0.05). Hematoxylin-eosin staining and transmission electron microscopy showed that the degree of myocardial injury in the Xuebijing group was slighter than that in the normal saline group.
    Conclusions Xuebijing injection may effectively mitigate inflammatory response and exert certain myocardial protection effect during the ECMO preservation of isolated empty beating pig hearts.

     

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