目的 探讨丙泊酚联合富氢液对脓毒症所致器官损伤及炎症反应的影响.方法 成年雄性C57BL/6小鼠140只,按随机数字表法分为假手术组、脓毒症组、丙泊酚组、富氢液组、联合治疗组,每组28只.采用盲肠结扎穿孔术(CLP)制备脓毒症动物模型;假手术组不进行盲肠结扎和穿孔,其余操作相同.术后1 h和6 h,丙泊酚组腹腔注射丙泊酚各50 mg/kg,富氢液组则注射含氢气生理盐水各5 mL/kg,联合治疗组注射丙泊酚后10 min再给予含氢气生理盐水.各组取20只小鼠观察术后7 d内存活情况.每组余8只小鼠于术后24 h取下腔静脉血及肺、肝和肾组织,采用酶联免疫吸附试验(ELISA)检测血清和各组织匀浆液中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及高迁移率族蛋白B1(HMGB1)含量,并观察各组织病理学改变及损伤评分.结果 脓毒症组术后1、2、3、5、7 d小鼠存活率分别为80%、40%、20%、10%、0%;给予丙泊酚或富氢液治疗后动物存活率明显提高,二者联合治疗可进一步将存活率提高至90%、75%、60%、55%、55%.与假手术组比较,脓毒症组血清和各组织中炎性因子水平明显增加,肺、肝、肾组织细胞可见变性、坏死、充血及炎性细胞浸润,各组织损伤评分也明显升高;给予丙泊酚或富氢液治疗后,血清和各组织中炎性因子水平明显下降,肺、肝、肾组织细胞变性、坏死、充血及炎性细胞浸润减少,各组织损伤评分也较脓毒症组明显降低,联合治疗组各指标较丙泊酚组、富氢液组进一步改善〔血TNF-α(ng/L):367±74比612±132、588±117,血IL-1β(ng/L):321±68比502±95、476±86,血HMGB1(μg/L):4.6±0.9比7.0±1.4、6.8±1.3;肺TNF-α(ng/g):307±70比512±132、488±102,肺IL-1β(ng/g):367±77比571±108、466±89,肺HMGB1(μg/g):5.1±1.0比7.8±1.7、7.1±1.5;肝TNF-α(ng/g):247±57比431±112、389±87,肝IL-1β(ng/g):267±58比417
Objective To investigate the effect of combining propofol with hydrogen on organ damage and inflammation of sepsis in cecal ligation and puncture (CLP) mice model.Methods One hundred and forty male C57BL/6 mice were randomly divided into groups (n = 28): sham group, CLP group, propofol group, H2 group, and propofol and H2 group. The sepsis was induced by CLP operation. Mice in sham group did the same operation with ligation and puncture. The mice of propofol group and propofol and H2 group were given 50 mg/kg propofol through tail vein at 1 hour and 6 hours after CLP and the mice of H2 group and propofol and H2 group were given 5 mL/kg H2-rich saline i.p. at 1 hour and 6 hours after CLP. The survival rates were observed during 7 days in twenty mice of each group. Inferior vena cava blood and part lung, liver and kidney tissue were collected for detection of the concentration of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and high mobility group box 1 (HMGB1) at 24 hours after CLP in the 40 animals left (eachn = 8). Then, the rest tissue of lung, liver and kidney tissue were harvested to test histopathology and histological score.Results The 1, 2, 3, 5, 7 days survival rate of septic mice were 80%, 40%, 20%, 10%, and 0%, respectively. The survival rate of animals increased significantly after propofol or hydrogen-rich treatment, and the combined treatment can further increase survival rate to 90%, 75%, 60%, 55%, and 55%, respectively. Compared with the sham group, inflammatory factors were significantly increased in blood and organ tissues, cell degeneration, necrosis, congestion and inflammatory cell infiltration in lung, liver and kidney, and tissues histological scores were significantly increased. The levels of inflammatory factors were reduced in blood and tissues, cell degeneration, necrosis, congestion and inflammatory cell infiltration were alleviated in lung, liver and kidney, and tissues histological scores were decreased after propofol or hydrogen-rich treatment