不同剂量盐酸胺溴索注射液对成人体外循环所致肺损伤的保护作用

Effects of ambroxoi hydrochloride on lung during cardiopulmonary bypass, analysis of 35 patients

目的探讨不同剂量盐酸胺溴索注射液对成人体外循环所致肺损伤的保护作用及机制。方法随机选择年龄20～70岁，心功能Ⅱ～Ⅲ级瓣膜置换患者36例，随机分为对照组（C组）、实验组：盐酸胺溴索注射液1组（M1组75mg）和盐酸胺溴索注射液2组（M2组150mg），每组各12例。实验组分别于麻醉后切皮前加入半量，另半量加入预充液中，对照组静脉注射等量生理盐水，分别于麻醉后切皮前（T1）、转流30min（T2）、开放升主动脉后30min（T3）、停机2h（T4）、停机6h（T51、术毕24h（T6），采集动脉血测定血浆肿瘤坏死因子-a（TNF—a）、丙二醛（MDA）浓度、IL—10含量和超氧化物歧化酶活力（SOD），并抽取动脉血进行血气分析，计算呼吸指数，做统计分析，比较3组的差别。并取肺组织，作组织学检查。结果3组TNF-α、MDA和SOD在CPB后均升高；M1组和M2组TNF—α于T2～T6时较C组低；M1组IL-10仅于T2时较C组升高；M2组则于T2～T5时较C组升高；M2组MDA于T2-T6时较C组和M1组低；C组SOD活性于T2～T5下降；M2组于T2～T5时较C组高。RI的变化：C组在T3～T6时较T1高，M1组和M2组在T3-T6时较C组低。组织学改变：CPB结束后30min：C组见部分肺泡结构破坏萎缩、上皮细胞脱落、肺泡腔内出血及大量白细胞聚集，液体渗出，间质水肿，毛细血管腔内炎性细胞浸润等现象，M1组和M2组见肺组织形态基本正常。结论体外循环可以导致肺功能的下降，一定剂量的盐酸胺溴索注射液可以在一定程度上抑制体外循环引起的炎性反应和氧化应激反应，发挥肺保护的作用，盐酸胺溴索注射液的肺保护作用在一定程度上呈剂量依赖性。

Objective To investigate the efficacy of ambroxol hydrochloride on lung during cardiopulmonary bypass. Methods Thirty-six ASA Ⅱ -Ⅲ patients, aged 20-70, scheduled for cardiac valve replacement were randomly divided into 3 equal groups： control group, ambroxol hydrochloride （mueosulvan） 1 group （M1 group） given mueosulvan 75 mg, and ambroxol hydrochloride （mucosulvan） 2 （M2 group） given mucosulvan 150 rag. Half dose of ambroxol hydrochloride was infused after skin incision and another half dose was added to the priming solution in M1 and M2 groups, and normal saline of the same volume was given instead of ambroxol hydrochloride in the control group. Blood samples were taken before skin incision （T1） , 30 min after start of CPB （T2） ,30 rain after aortic declamping （T3） ,2 h after termination of CPB （T4）, 6h after termination of CPB （TS）, and 24 h after operation （T6） to examine the plasma concentrations of tumor necrosis faetor-α（TNF-α）, interleukin-10 （IL-10）, and malondialdehyde （MDA）, and superoxide dismutase （SOD）activity. Arterial blood samples were collected for blood gas analysis. Respiratory index （RI） was calculated. Lung biopsy was performed to observe the histoligical change. Results The levels of TNF-α, MDA, and SOD all increased after CPB in these 3 groups （P 〈 0.05-0.01）. The levels of TNF-α at the time points T2-T6 in the M1 and M2 groups were lower than those in the control group （P〈 0.05-0.01）. The IL-10 level at the time point T2 was higher in M1 group than in the control group （P 〈 0.05）, whereas the IL-10 levels at the time points T2-T5 in the M2 group were higher than those in the contgrol group （all P 〈 0.05）; and the levels of MDA at the time points T2-T6 in the M2 group were all lower than those in the M1 and control groups （all P 〈 0.05）. The SOD activity at the time points T2-T5 during CPB decreased in the control group, and were higher in the M2 group than those in the control group （all P 〈 0.05）. The RI at the time points T3-T6 were higher than at the time point T1 in the contgrol group （all P 〈 0.05）, and the RI levels at T3-T6 in the M1 and M2 groups were lower than in the control group （all P 〈 0.05）. Lung biopsy showed that 30 minutes after CPB the pulmonary architectture was demolished and atrophiaed, alveolar cell defluxion, hemorrhage, inflammatory cell accumulation, liquid exosmosis in alveolar space, interstitial edema, engorgement and distension in capillary lumen were found in the control group. However, histological evaluation revealed normal pulmonary architeetture in the M1 and M2 groups. Conclusion CPB can lead to lung injury, ambroxol hydroehloride is effective in reducing CPB-induced inflammatory response and ischemic resperfusion injury in a dose-dependent manner.