Pang Qing-feng, Ji Yong, Bermúdez-Humarán Luis G, Zhou Qiao-mei, Hu Gang, Zeng Yinming
Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.
J Surg Res. 2009 May 1;153(1):39-45. doi: 10.1016/j.jss.2008.03.042. Epub 2008 Apr 28.
To investigate the protective effects of a heme oxygenase-1 (HO-1)-secreting Lactococcus lactis (LL-HO-1) on mucosal injury induced by hemorrhagic shock in rats.
The ability of recombinant LL-HO-1 to secrete biological active HO-1 in the rat intestine was determined in situ after 3 d of daily intragastric administration. The therapeutic potential of LL-HO-1 strain was then evaluated on mucosal injury induced by hemorrhagic shock in rats. After successful resuscitation, mean arterial blood pressure was recorded at 5, 10, 20, and 30 min. One hour after resuscitation, the ileum was harvested for evaluation of mucosal injury by blinded microscopic inflammatory score (Chiu's grade 0-5), myeloperoxidase activity, bacterial translocation, and by the secretion of pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-10, respectively).
Intragastric administration of HO-1-secreting L. lactis strain led to bioactive delivery of HO-1 at intestinal mucosa and significantly enhanced mean arterial blood pressure and interleukin-10 levels. Moreover, intragastric administration of LL-HO-1 significantly decreased Chiu's score, myeloperoxidase activity, bacterial translocation, and tumor necrosis factor-alpha levels when compared with rats treated with the wild-type strain. The protective effect of recombinant LL-HO-1 could be abolished by co-administration of a HO-1 inhibitor, the zinc protoporphyrin-IX.
These results suggest that intragastric administration with HO-1-secreting L. lactis reduces mucosal injury induced by hemorrhagic shock.
研究分泌血红素加氧酶-1(HO-1)的乳酸乳球菌(LL-HO-1)对大鼠失血性休克所致黏膜损伤的保护作用。
每日灌胃给药3天后,原位测定重组LL-HO-1在大鼠肠道中分泌生物活性HO-1的能力。然后评估LL-HO-1菌株对大鼠失血性休克所致黏膜损伤的治疗潜力。成功复苏后,在5、10、20和30分钟记录平均动脉血压。复苏1小时后,采集回肠,通过盲法显微镜炎症评分(Chiu分级0-5)、髓过氧化物酶活性、细菌移位以及促炎和抗炎细胞因子(分别为肿瘤坏死因子-α和白细胞介素-10)的分泌来评估黏膜损伤。
灌胃分泌HO-1的乳酸乳球菌菌株导致HO-1在肠黏膜处实现生物活性递送,并显著提高平均动脉血压和白细胞介素-10水平。此外,与野生型菌株处理的大鼠相比,灌胃LL-HO-1可显著降低Chiu评分、髓过氧化物酶活性、细菌移位和肿瘤坏死因子-α水平。重组LL-HO-1的保护作用可通过共同给予HO-1抑制剂原卟啉锌-IX而消除。
这些结果表明,灌胃分泌HO-1的乳酸乳球菌可减轻失血性休克所致的黏膜损伤。