乌司他丁联合ghrelin对内毒素血症大鼠肠功能障碍的影响

目的观察乌司他丁(UTI)联合ghrelin(GHL)对内毒素血症大鼠肠功能障碍的影响,探讨UTI联合GHL改善内毒素血症大鼠肠功能的作用及其可能机制。方法以内毒素(LPS)15 mg/kg腹腔注射大鼠作为内毒素血症动物模型。将60只雄性SD大鼠随机等分为对照组(CON组)、LPS组、UTI组、GHL组、UTI+GHL组,采用HE染色、RealTime-PCR、小肠葡聚糖蓝-2000(BD-2000)推进率和ELISA等方法在12 h及24 h观察各组大鼠小肠屏障功能、小肠运动功能以及炎症介质TNF-α、IL-6、HMGB1等变化。结果 HE染色结果显示UTI+GHL组、UTI组与LPS组相比能不同程度减轻回肠结构损伤,且UTI+GHL组更明显(P0.05)。UTI组和UTI+GHL组在RD-5和TFF3 mRNA表达水平方面较LPS组有显著提高(P0.05),且UTI+GHL组升高明显(P0.05)。GHL组和UTI+GHL组较LPS组小肠运动功能均显著升高,且UTI+GHL组更为明显(P0.05)。UTI+GHL组、UTI组、GHL组与LPS组相比均能显著降低TNF-α、IL-6、HMGB1等炎症因子表达(P0.05),且在肠黏膜组织中发现了类似结果。结论 UTI联合GHL可通过抑制内毒素血症时全身炎症反应及肠组织局部炎症反应,明显改善肠屏障及提高肠运动功能。

Ulinastain with ghrelin improves small intestine dysfunction in endotoxemia rats

Objective To evaluate the antiinflammatory effect of ulinastain（UTI） with ghrelin （GHL）on amelioration of small intestine dysfunction and its possible mechanisms in endotoxemia rats. Methods Animals were received intraperitoneal injection with lipopolysaccha- ride（LPS,15 mg/kg） as a endotoxemia model. 60 male SD rats were randomly divided into control group（ CON group）,LPS group, UTI group, GHL group, and UTI ＋ GHL group. Microstructure of small intestinal submucosa was observed with HE staining. Dextran blue-2000 （ BD-2000 ） was drenched for calculation of propulsion rate of the small intestine. The level of tumor necrosis factorc~ （ TNF-a ）, IL-6 and HMGB1 in serum and small Intestinal mucosal tissue were determined by enzyme linked immunosorbent assay（ELISA）. RealTime-PCR was administrated for detection of rat defensin-5 mRNA（ RD-5 ）and trefoil factor family-3 （TFF-3）mRNA. All above measurement were taken re- spectively at 12 hours and 24 hours after LPS injection. Results HE staining shows that UTI ＋ GHL group significantly alleviate the damage of intestinal microtructure caused by LPS when compared with UTI group and GHL group. The UTI ＋ GHL group markedly increased expres- sion of RD-5 and TFF3 mRNA than those of UTI and GHL group in small Intestinal mucosal tissue （ P 〈 O. 05 ）. Both the GHL group and the UTI ＋ GHL group significantly enhanced the function of intestine motility, but the propulsion rate of UTI ＋ GHL group was significant higher than that of GHL group（P 〈 O. 05）. In LPS group,the level of TNF-a,IL-6 and HMGB1 both in serum and intestinal mucosa tissue were markedly increased （P 〈 O. 05 ）, but those of UTI group, GHL group and UTI ＋ GHL group were significantly decreased when compare to LPS group after the drugs administration at 12 and 24 hours. Conclusion UTI combined with GHL can significantly improve the intestinal func- tion of mucosal barrier and the motor through the inhibition of both systemic and intestinal mucosal inflammatory reaction in the process of en- dotoxemia.