埃索美拉唑对大鼠创伤性脑损伤后肠黏膜屏障损伤的作用

目的 探讨埃索美拉唑对大鼠创伤性脑损伤(TBI)后应激性肠黏膜损伤的保护作用.方法 雄性Wistar大鼠54只,随机分为3组,各18只:TBI组埃索美拉唑预处理组质子泵抑制(PPI)组],假手术组(对照组).TBI组动物制模前1 h皮下注射埃索美拉唑0.1 mg(0.25 mi/100 g),TBI组和对照组术前1 h注射等量的生理盐水(0.25 ml/100 g).各组动物分别在术后3、12、24 h心脏取血后处死(各时间点6只),处死后取脑组织和肠黏膜组织观察形态学改变,测定肠黏膜组织二胺氧化酶(DAO)、超氧化物歧化酶(SOD)、丙二醛、羟自由基、髓过氧化物酶(MPO)的含量,同时检测血清中DAO活性及异硫氰酸荧光素(FITC)浓度.结果 (1)PPI组肠黏膜损伤程度较TBI组轻.(2)TBI组损伤后随时间延长血清FITC-右旋糖苷外渗逐渐增加,以24 h时间点最为明显(P＜0.01),PPI组较TBI组轻(3720±401)ng/ml比(5230±489)ng/ml P＜0.05].(3)肠黏膜组织中DAO的活性随时间增加逐渐下降,以24 h点最为明显,PPI组下降幅度高于TBI组,血清变化与之相反.(4)TBI组肠黏膜组织中SOD、GSH随时间延长逐渐下降,以24 h点最为明显(P＜0.05),PPI组SOD和GSH分别高于TBI组(U/mgprot:13.0±2.4和208±48比10.2±2.8和140±46,均P＜0.05).(5)TBI组肠黏膜组织中羟自由基、丙二醛、MPO随时间延长逐渐升高,以24 h点最为明显(P＜0.05),PPI组羟自由基、丙二醛和MPO均低于TBI组(U/mgprot:108±8、6.2±0.6、1.53±0.52比150±8、7.7±0.9、1.93±0.53,均P＜0.05).结论 创伤性脑损伤可能导致应激性肠黏膜损伤,氧自由基在致肠黏膜损伤中起重要作用,埃索美拉唑通过抗氧化和抑制中性粒细胞活性可以减轻应激性肠黏膜损伤.

Effect of esomeprazole upon intestinal mucosal damage following traumatic brain injury in rats

Objective To explore the protective effect of esomeprazole upon stress-related intestinal mucosal damage following traumatic brain injury (TBI) in rats.Methods Male Wistar rats were randomly divided into three groups:groups A and B served as TBI models and group C was designated as a normal control (shame operation).In group B rats were treated subcutaneously with esomeprazole prior to TBI while groups A and C rots were treated with an equivalent amount of normal saline.During the observation period,the morphological changes of brain tissue and intestinal mucosa were observed.And the intestinal mueosal permeability to flnoreseein isothiocyanate (FITC)-labeled dextran and diamine oxidase (DAO) activity were assessed.The activities of superoxide dismutase (SOD),myeloperoxidase (MPO) and the levels of malondiatdehyde (MDA),reduced glutathione(GSH) and hydroxyl radical (OH·) were measured.Results (1)During the observation period of TBI,the intestinal mucosal was damaged,but there was improvement in group PPI.(2) FITC-dextran leakage increased after TBI and peaked at 24 h (P＜0.01);its level of (3720±401) ng/ml in group PPI was lower than that in group TBI (5230±489) ng/ml (P＜0.05).(3)The DAO activity in mucesa decreased and the decline was the greatest at 24 h (P＜0.05),its level of (0.44±0.11) ng/ml in group PPI at 24 h was higher than that in group TBI (0.31±0.07) ng/ml (P＜0.05);while the DAO activity in serum increased significantly.(4) The activity of SOD and the level of GSH in intestinal mucosal started to decrease at 3 h and the decline was the greatest at 24 h (P＜0.05),their levels were (10.2±2.8)U/mgprot and (140±46) mg/gprot respectively in group TBI,a remarkable drop in comparison with those of PPI group (13.0 s 2.4) U/mgprot and (208±48) U/gprot (P＜0.05).(5) The levels of OH',MDA and MPO in intestinal mucosal increased and peaked at 24 h (P＜0.05),the respective levels in group PPI(108±8),(6.2±0.6) and (1.53±0.52) U/mgprot and those in the TBI group(150 s 8),(7.7±0.9),(1.93±0.53) U/mgprot,demonstrated that there was a remarkable rise (P＜0.05).Conclusion Traumatic brain injury may lead to stress-related intestinal mucosal damage.Oxygen free radicals play an important role in intestinal mucosal barrier damage.Esomeprazole attenuates the damage of intestinal mucosal barrier by antioxidant effect and inhibiting the activity of neutrophil.