早期应用去甲肾上腺素的液体复苏方案对脓毒性休克大鼠肺脏的作用

The effect of fluid resuscitation with early use of norepinephrine on lung of septic shock rat inducedby LPS

目的研究早期与延迟应用去甲肾上腺素的两种液体复苏方案对脓毒性休克大鼠肺损伤的影响。方法60只Wistar大鼠随机（随机数字法）分成4组：健康对照组（A组，n=15），休克对照组（B组，n=15），传统液体复苏组（C组，n=15），早期应用去甲肾上腺素组（D组，n=15），所有大鼠给予经1：3气管插管机械通气，相同呼吸机模式及参数。LPS静脉注射建立脓毒性休克大鼠模型，C组于液体复苏0．5h后应用去甲肾上腺素，D组于液体复苏同时应用去甲肾上腺素，记录各组大鼠生命体征、补液量及去甲肾上腺素用量。2h后处死大鼠，进行血气分析，HE染色观察肺组织形态学变化，ELISA检测肺泡灌洗液及血清中炎性介质的表达，检测肺组织中髓过氧化物酶、超氧化物歧化酶及丙二醛表达。计量资料以均数±标准差（x-±s）表示，采用SPSS13．0统计软件分析，组问比较采用t检验，以P〈0．05为差异具有统计学意义。结果早期应用去甲肾上腺素与传统补液方案比较明显减少了达到目标血压所需的补液量，使氧合指数进一步改善，同时降低了血乳酸水平（P〈0．05）；HE染色结果显示早期应用去甲肾上腺素使肺水肿程度明显减轻，肺组织中炎性细胞侵润程度、肺泡充血情况得到明显改善；早期应用去甲肾上腺素和传统补液方案均使血清和肺泡灌洗液中的促炎介质白介素-6、白介素-8、肿瘤坏死因子一仪表达水平下调，但早期应用去甲肾上腺素使促炎介质表达下降更为明显，与传统补液比较差异具有统计学意义（P〈0．05）；早期应用去甲肾上腺素仅使髓过氧化物酶表达较传统补液组及休克对照组明显下降，两种补液方案对超氧化物歧化酶和丙二醛表达均无明显改善。结论早期应用去甲肾上腺素的液体复苏方案与传统补液方案比较从多层面改善了脓毒性休克大鼠肺损伤的程度。

Objective To explore the efficacy of different modes of fluid resuscitation （early or delayed use of norepinephrine） on lung injury of septic shock rat induced by LPS. Methods A total of 60 male Wistar rats were randomly （random number） divided into 4 groups： the normal control group （group A, n = 15）, septic shock control group （ group B, n = 15） , conventional fluid resuscitation group （group C, n = 15 ） , fluid resuscitation with early using of norepinephrine group （ group D, n = 15）. All rats were mechanically ventilated with the same parameters. In the group C, norepinephrine was used 30 min after fluid resuscitation. In the group D, norepinephrine was used at the beginning of fluid resuscitation. Vital signs, volume of fluid infused and dosage of norepinephrine were recorded. Rats were sacrificed 2 h later and blood samples were collected for blood gas analysis. The lung tissues and BALF were collected. Pathological changes of the lung tissues were observed under light microscope. The levels of MPO, SOD andMDA were detected. The levels of IL-6, IL-8 and TNF-ct in BALF and in serum were detected by using ELISA. Results Compared with group C, the mean volume of fluid infusion to achieve target blood pressure was decreased, oxygenation index was improved and the level of blood lactic acid were decreased in group D （P 〈 O. 05）. liE staining indicated that inflammatory cells were decreased, pulmonary edema and alveolar walls hyperemia were alleviated in group D in comparison with group C. Inflammatory cytokines （IL-6, IL-8 and TNF-α） in BALF and in serum were significantly decreased in group D compared with group C （ P 〈 0. 05）. Levels of MPO were decreased in group D compared with group B and group C. However, early using of norepinephrine had limited effect on the levels of SOD and MDA. Conclusions The current study demonstrated that fluid resuscitation with early use of norepinephrine exhibited a protective effect on lung injuries induced by LPS.