【作者】 董硕；

【导师】 张春芳；

【作者基本信息】 中南大学 ， 外科学， 2012， 博士

【摘要】 目的检测开胸手术围术期患者血清标志物肺表面活性物质相关蛋白-A (surfactant-associated protein A, SP-A)、细胞间粘附因子1(intercellular adhesion molecule, ICAM-1)、丙二醛(malondialdehyde, MDA).超氧化物歧化酶(superoxide dismutase, SOD)与肺功能(pulmonary function)、动脉血气(arterial blood gas)等指标,研究不同剂量盐酸氨溴索对上述指标变化的影响。为开胸手术围术期盐酸氨溴索剂量的临床应用提供新的依据。方法(1)收集湘雅2011年5月-2012年2月胸外科行开胸手术的患者80例。(2)采用分组、双盲、空白对照的方法,以入选病人随机分为A、B、C、D四组,A组为空白对照组(不使用试验药物)；B组为小剂量组(3mg/(kg.d)组)；C组为中剂量组(9mg/(kg.d)剂量组)；D组为大剂量组(15mg/(kg.d)组)。试验组病人术前3天起采用相应剂量的盐酸氨溴索针(规格2m1：15mg)至术后3天。(3)在试验前(T1a)、术中(T1b)、试验第六天(T1c)进行动脉血气分析,记录其氧分压(PaO2,mmHg)水平；在入院即刻(T2a)、术前即试验第三天(T2b)、术后第三天(T2c)对患者进行肺功能试验,记录一秒钟用力呼气容积(FEV1)与用力肺活量(FVC)比值(FEV1/FVC)(?)勺水平；在试验前(T3a)、术前即试验第三天(T3b)、术后30min(T3c)、术后第三天(T3d)测量静脉血中肺表面活性物质相关蛋白A(SP-A)的水平；在试验前(T4a)、术前即试验第三天(T4b)、术后120min(T4c)、术后第三天(T4d)测量静脉血中超氧化物歧化酶(SOD)、细胞间粘附因子(ICAM-1)和丙二醛(MDA)的水平。(4)对所有血清标本用酶联免疫吸附试验法(enzyme-linked immunosorbent assay, ELISA)检测(?)SP-A、MDA、SOD、ICAM-1水平。(5)对试验结果、临床资料等应用SPSS17.0软件进行统计学分析,P<0.05为差异有统计学意义。结果(1)PaO2:T1a, T1b时刻PaO2水平,ABCD组间两两比较无统计学差异(P>0.05)；T3c时刻Pa02水平,A组与B组比较、C组与D组比较无统计学差异(P>0.05),A组与C、D组比较有统计学差异(P<0.05)；B组与C、D组比较有统计学差异(P<0.05)。(2) FEV1/FVC:T2a、T2b时刻FEV1/FVC水平,ABCD组间两两比较无统计学差异(P>0.05)；T3c时刻FEV1/FVC水平,B、C、D组高于A组(P>0.05),B组与C组比较无统计学差异(P>0.05)；D组高于B、C组(P<0.05)。(3)SP-A：BCD组T3b、T3c、T3d时刻SP-A含量较A组低(P<0.05)；T3b、T3c时刻,B组与C组、C组与D组、B组与D组的SP-A水平相比无统计学差异(P>0.05)；Y3d时刻,D组SP-A水平明显低于B组与C组(P<0.05),C组SP-A水平与B组相比无统计学差异(P>0.05)。(4) ICAM-1、SOD、MDA:BCD组T4b T4c T4d时刻ICAM-1、MDA含量与A组相比明显降低,SOD含量则相应明显升高(p<0.05)。D组T4b T4c T4d时刻ICAM-1、MDA含量与BC组相比明显降低,SOD含量则相应明显升高(P<0.05)。C组T4b T4c T4d时刻ICAM-1、 MDA、SOD含量与B组相比无统计学差异(P>0.05)。结论1.围术期小剂量盐酸氨溴索应用,对围术期患者动脉血氧分压水平无明显影响,应用中剂量与大剂量盐酸氨溴索可有效提高患者术后血氧分压水平,且效果相同。2.围术期应用盐酸氨溴索可有效提高患者术后FEV1/FVC水平,从而改善肺顺应性,大剂量应用盐酸氨溴索,其改善效果更为明显。3.围术期使用盐酸氨溴索可降低外周血中SP-A水平,大剂量盐酸氨溴索的应用对术前及术后30min降低SP-A水平的作用不明显,而在术后三天内,可显著降低SP-A水平,与其对炎性因子、抗炎因子的影响综合分析,炎性反应与外周血SP-A水平并非成正相关。4.盐酸氨溴索可有效调控MDA、SOD、ICAM-1因子的含量,从而发挥其抗炎、抗氧化作用,且药物起效时间小于三天,其抗炎、抗氧化作用在大剂量应用时效果更为明显。更多还原

【Abstract】 Objective Detect the serum markers (surfactant-associated protein A, intercellular adhesion molecule, malondialdehyde, superoxide dismutase) and clinical examination indexes (pulmonary function, arterial blood gas) of the postoperative thoracotomy patients, in order to research the relation between the markers above and the usage of mucosolvan with different dosage. So as to provide new evidence for the clinical usage of ambroxol in the patients undergoing thoracotomy.Methods (1) Collected80cases of thoracotomy patients of XiangYahospital during2011.05-2012.02.(2) Based on the method of randomized grouping double-blind,blank control.Divided the patients sellected into four groups (A、B、C、D). group A is blank controled group (without using drugs); group B is small dosage group (3mg/(kg.d)); group C is middle dosage group (9mg/(kg.d)); group D is large dosage group (15mg/(kg.d)).To use corresponding dosage of ambroxol (2ml:15ml) on three days before the surgery to three days after the surgery, altogether six days.(3) Testing the arterial blood gas on pre-test (T1a),intraopration (T1b),the sixth days of the test (T1c), and record the level of oxygen partial pressure (PaO2, mmHg); Testing the pulmonary function on pre-test (T2a),intraopration (T2b),the sixth days of the test (T2c), and record the level of FEV1/FVC; Testing the SP-A on pre-test (T3a)、 intraopration (T3b)、30minutes after the surgery (T3c), the sixth days of the test (T3d); Testing the level of MDA,SOD,ICAM-1on pre-test (T4a),intraopration (T4b),two hours after surgery (T4c),the sixth days of the test (T4d)(4) Test the level of SP-A,MDA,SOD by the mean of Enzyme-linked Immunosorbent Assay.(5) Stafistical analysis was performed using SPSS statistical software package (17.0). P values≤0.05indicated statistically significant difference.Results (1) PaO2:At the moment of T1a and T1b, the level of PaO2in ABCD group is no significant difference with each other(P>0.05); at T3c, there is no significant difference (P>0.05) at the level of PaO2in group A compared with group B and group C compared with group D, group A compared with group C and group D had statistical differences (P<0.05); group B compared with group C and D had statistical differences (P<0.05).(2) FEV1/FVC:Between any two of the T2a, T2b time the FEV1/FVC level, group ABCD had no significant difference with each other (P>0.05); the FEV1/FVC level at T3c time, Group BCD was higher than that in group A (P>0.05), Group B had no significant difference compared with group C (P>0.05); group D was higher than group BC(P <0.05).(3) SP-A:At T3b T3c and T3d, the SP-A of group BCD was lower compared with group A (P<0.05); at T3b and T3c, the level of SP-A in group B and group C, group C and group D, group B and group D had no significant difference (P>0.05); at T3d, the level of SP-A in group D was significantly lower than group B and group C (P<0.05), there was no significant difference between group C and group B (P>0.05).(4) ICAM-1、SOD. MDA:At T4b T4c T4d, the content of MDA and ICAM-1in group A was significantly higher than that of group BCD,and the level of SOD was significantly higher (P<0.05). At T4b T4c T4d,the content of MDA and ICAM-1in group D was lower than that of group BC, and the level of SOD was significantly higher (P<0.05). At T4b T4c T4d moment,there was no significant difference of ICAM-1、 MDA. SOD between group C and group B (P>0.05).Conclusion (1) Small dose ambroxol application in perioperation had no significant effect on the perioperative period in patients with arterial oxygen tension levels, while medium dose and high-dose application of ambroxol can improve the postoperative blood oxygen levels, and has the same effect both.(2) Perioperative application of ambroxol can effectively improve the level of FEV1/FVC postoperative, thereby improving lung compliance, the improvement is more obvious while use large dose of ambroxol.(3) The perioperative ambroxol may reduce the level of SP-A in peripheral blood, large doses of ambroxol application preoperative and postoperative30min to reduce the role of SP-A levels is not obvious, and within three days after surgery, can significantly reduce SP-A level, and the analysis of the inflammatory factors, anti-inflammatory factors and peripheral blood SP-A levels indicates that the Inflammatory response and SP-A in peripheral blood are not positively correlated.(4) Ambroxol can regulate the content of MDA,SOD and ICAM-1effectively, thus play the role of anti-inflammatory and antioxidant, its onset time is less than three days, the anti-inflammatory, anti-oxidation effect is more obvious while large dose application.更多还原