Lü Dong, Cui Pei-lin, Yang Zhao-xu
Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Zhonghua Yi Xue Za Zhi. 2009 Nov 3;89(40):2867-70.
To explore the protective effect of esomeprazole upon stress-related intestinal mucosal damage following traumatic brain injury (TBI) in rats.
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 rats 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 mucosal permeability to fluorescein isothiocyanate (FITC)-labeled dextran and diamine oxidase (DAO) activity were assessed. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the levels of malondialdehyde (MDA), reduced glutathione (GSH) and hydroxyl radical (OH(*)) were measured.
(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 mucosa 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 +/- 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 +/- 8), (7.7 +/- 0.9), (1.93 +/- 0.53) U/mgprot, demonstrated that there was a remarkable rise (P < 0.05).
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.
探讨埃索美拉唑对大鼠创伤性脑损伤（TBI）后应激相关肠黏膜损伤的保护作用。
雄性Wistar大鼠随机分为三组：A组和B组为TBI模型组，C组为正常对照组（假手术组）。B组大鼠在TBI前皮下注射埃索美拉唑，A组和C组大鼠注射等量生理盐水。观察期内，观察脑组织和肠黏膜的形态学变化。评估肠黏膜对异硫氰酸荧光素（FITC）标记右旋糖酐的通透性及二胺氧化酶（DAO）活性。检测超氧化物歧化酶（SOD）、髓过氧化物酶（MPO）活性及丙二醛（MDA）、还原型谷胱甘肽（GSH）、羟自由基（OH(·)）水平。
（1）TBI观察期内，肠黏膜受损，但质子泵抑制剂（PPI）组有改善。（2）TBI后FITC - 右旋糖酐渗漏增加，24 h达峰值（P < 0.01）；PPI组水平（3720 ± 401）ng/ml低于TBI组（5230 ± 489）ng/ml（P < 0.05）。（3）黏膜中DAO活性降低，24 h下降最明显（P < 0.05），PPI组24 h时水平（0.44 ± 0.11）ng/ml高于TBI组（0.31 ± 0.07）ng/ml（P < 0.05）；而血清中DAO活性显著增加。（4）肠黏膜中SOD活性和GSH水平在3 h开始下降，24 h下降最明显（P < 0.05），TBI组分别为（10.2 ± 2.8）U/mgprot和（140 ± 46）mg/gprot，与PPI组（13.0 ± 2.4）U/mgprot和（208 ± 48）U/gprot相比显著降低（P < 0.05）。（5）肠黏膜中OH(·)、MDA和MPO水平升高，24 h达峰值（P < 0.05），PPI组分别为（108 ± 8）、（6.2 ± 0.6）和（1.53 ± 0.52）U/mgprot，TBI组为（150 ± 8）、（7.7 ± 0.9）、（1.93 ± 0.53）U/mgprot，显示有显著升高（P < 0.05）。
创伤性脑损伤可导致应激相关肠黏膜损伤。氧自由基在肠黏膜屏障损伤中起重要作用。埃索美拉唑通过抗氧化作用和抑制中性粒细胞活性减轻肠黏膜屏障损伤。
