Jiang Longyuan, Yang Lianhong, Zhang Meng, Fang Xiangshao, Huang Zitong, Yang Zhengfei, Zhou Tianen
Department of Emergency Medicine, The Memorial Hospital of Sun Yat-sen, Sun Yat-sen University, Guangzhou, China.
Indian J Med Res. 2013 Dec;138(6):904-11.
BACKGROUND & OBJECTIVES: The gut contains some endogenous and exogenous microorganisms that can become potential pathogens of sepsis under certain circumstances. Therefore, the integrity and normal function of gut barrier is important for preventing the development of sepsis. The present study was designed to assess the effects of ulinastatin, a urinary trypsin inhibitor on gut barrier function and mortality in experimental sepsis.
Male Sprague-Dawley rats were subjected to ceacal ligation and puncture (CLP) or sham procedure. Rats were then treated with ulinastatin 50,000 U/kg/day or saline. The mortality rate was determined. Histology, apoptosis assays, and PCR were performed using ileum specimens at 3, 6, and 12 h following CLP. Serum levels of tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) were also measured at 0, 3, 6, and 12 h following CLP.
Compared with the saline-treated CLP rats, the ulinastatin CLP rats had significantly increased survival time (P<0.05), lower histopathological scores of intestinal injury (P<0.05), reduced apoptosis detected by terminal deoxynucleotidyl transferase dUTP nick end labelling assay and caspase 3 activity (P<0.01). Moreover, RD-5 mRNA expression was significantly higher in ulinastatin-treated CLP animals than saline controls (P<0.05). These results suggested a preserved integrity and function of the gut barrier. Significantly lower plasma TNFα and IL-6 levels were detected in CLP rats with ulinastatin treatment, which contributed to increased survival time.
INTERPRETATION & CONCLUSIONS: Our results suggest that ulinastatin has a therapeutic potential to prevent gut barrier dysfunction in the early stage of sepsis, thereby improving the outcome of sepsis. Further studies need to be done to understand the mechanism of action of ulinastatin.
肠道内存在一些内源性和外源性微生物，在某些情况下它们可能成为脓毒症的潜在病原体。因此，肠道屏障的完整性和正常功能对于预防脓毒症的发生至关重要。本研究旨在评估尿胰蛋白酶抑制剂乌司他丁对实验性脓毒症肠道屏障功能及死亡率的影响。
将雄性Sprague-Dawley大鼠行盲肠结扎穿孔术（CLP）或假手术。然后大鼠分别接受50000 U/kg/天的乌司他丁或生理盐水治疗。测定死亡率。在CLP术后3、6和12小时，使用回肠标本进行组织学、凋亡检测及PCR。在CLP术后0、3、6和12小时也检测血清肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）水平。
与生理盐水治疗的CLP大鼠相比，乌司他丁治疗的CLP大鼠存活时间显著延长（P<0.05），肠道损伤的组织病理学评分更低（P<0.05），末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测到的凋亡及半胱天冬酶3活性降低（P<0.01）。此外，乌司他丁治疗的CLP动物中RD-5 mRNA表达显著高于生理盐水对照组（P<0.05）。这些结果提示肠道屏障的完整性和功能得以保留。乌司他丁治疗的CLP大鼠血浆TNFα和IL-6水平显著降低，这有助于延长存活时间。
我们的结果表明，乌司他丁在脓毒症早期具有预防肠道屏障功能障碍的治疗潜力，从而改善脓毒症的预后。需要进一步研究以了解乌司他丁的作用机制。
