Experimental study on the role of IL-10 in improving donor lung function after ex vivo lung perfusion in rats of cardiac death
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摘要:
目的 探讨白细胞介素(IL)-10对心脏死亡大鼠离体肺灌注(EVLP)后供肺功能的影响。 方法 将20只成年雄性SD大鼠随机分成单纯灌注组(A组)和改良灌注组(B组)，每组10只。A组采用A灌注液(灌注液未添加IL-10)进行灌注，B组采用B灌注液(灌注液中添加IL-10)进行灌注，建立大鼠心脏死亡供肺EVLP模型。比较两组供肺外观及供肺组织干重/湿重(D/W)比值、供肺功能和代谢状态、供肺形态学表现和供肺炎症标志物水平。 结果 灌注结束后，A组供肺全肺明显水肿，顺应性差，气道内涌出大量水肿液，而B组未见明显水肿，顺应性较好。与A组比较，B组肺组织D/W比值较高(P < 0.05)。两组肺静脉血氧分压均在灌注2 h时达到最高，组间比较差异无统计学意义(P > 0.05)。与A组比较，B组肺动脉压升高速度较慢，灌注结束时肺动脉压较低; 且灌注液中乳酸水平下降(均为P < 0.05)。A组肺泡结构大量破坏，细胞数量稀少，B组肺泡结构相对正常，未见明显细胞水肿。A组供肺细胞凋亡较多，B组供肺未见明显细胞凋亡现象。两组灌注4 h后单核细胞趋化蛋白(MCP)-1、IL-6水平均升高，IL-4均降低(均为P < 0.05)，肿瘤坏死因子(TNF)-α、IL-1α和诱导型一氧化氮合酶(iNOS)变化无统计学意义(均为P > 0.05)。 结论 IL-10可通过减少细胞凋亡改善心脏死亡大鼠EVLP后供肺的功能。 -
关键词:
- 离体肺灌注(EVLP) /
- 肺移植 /
- 心脏死亡器官捐献(DCD) /
- 细胞凋亡 /
- 白细胞介素 /
- 诱导型一氧化氮合酶(iNOS) /
- 单核细胞趋化蛋白(MCP) /
- 肿瘤坏死因子 /
- 供肺
Abstract:Objective To evaluate the effect of interleukin (IL)-10 on donor lung function after ex vivo lung perfusion (EVLP) in rats of cardiac death. Methods Twenty adult male SD rats were randomly divided into the simple perfusion group (group A, n=10) and modified perfusion group (group B, n=10). Perfusate A (without IL-10) and perfusate B (supplemented with IL-10) was administered in group A and B, respectively. The EVLP rat models of cardiac death were established. The appearance of donor lung, dry-to-wet (D/W) ratio of donor lung tissues, the function and metabolism of donor lung, the morphology of donor lung and the levels of inflammatory markers of donor lung were statistically compared between two groups. Results After perfusion, evident edema of the whole donor lung, poor compliance and a large amount of edema fluid discharged from the airway were observed in group A, whereas no obvious edema and good compliance were found in group B. Compared with group A, the D/W ratio of lung tissues in group B was higher (P < 0.05). In both groups, the pulmonary vein partial pressure of oxygen reached the peak at 2 h after perfusion, which did not significantly differ between two groups (P > 0.05). In group B, the pulmonary artery pressure was increased at a lower speed and significantly lower after perfusion, and the lactic acid level in the perfusate was significantly lower than those in group A (all P < 0.05). In group A, the alveolar structure was largely destroyed and the cells was rare. In group B, the alveolar structure was relatively normal without evident cell edema. The incidence of cell apoptosis of donor lung was high in group A, whereas no obvious cell apoptosis of donor lung was noted in group B. After perfusion for 4 h, the levels of monocyte chemoattractant protein (MCP)-1 and IL-6 were significantly increased, the IL-4 levels were remarkably decreased (all P < 0.05), but the levels of tumor necrosis factor (TNF)-α, IL-1α and inducible nitric oxide synthase (iNOS) did not significantly change in both groups (all P > 0.05). Conclusions IL-10 may improve the function of donor lung after EVLP in rat of cardiac death by reducing cell apoptosis. -
图 2 两组供肺外观及供肺组织D/W比值比较
注：A、B图示A、B两组供肺外观; C图示两组供肺组织D/W比值比较，与A组比较，aP < 0.05。
Figure 2. Appearance of donor lung and comparison of D/W ratio of donor lung tissues between two groups
图 3 两组肺静脉血氧分压、肺动脉压及乳酸水平比较
注：A图示两组肺静脉血氧分压变化(10 mmHg=1.33 kPa); B图示两组肺动脉压变化，与A组比较，aP < 0.05;C图示两组乳酸水平变化，与A组比较，aP < 0.05。
Figure 3. Comparison of pulmonary vein partial pressure of oxygen, pulmonary artery pressure and lactic acid level between two groups
图 4 两组供肺的病理学表现及细胞凋亡情况
注：A、B图示供肺组织病理学表现(HE，×100);C、D图示供肺组织细胞凋亡情况(TUNEL，×200)。
Figure 4. Pathological findings and cell apoptosis of donor lung in two groups
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