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乌司他丁对盲肠结扎穿孔术诱导的大鼠脓毒症模型小肠损伤及肥大细胞脱颗粒的影响

The effect of ulinastatin on the small intestine injury and mast cell degranulation in a rat model of sepsis induced by CLP.

作者信息

Zhang Yi-Jing, Li Ming, Meng Mei, Feng Mei, Qin Cheng-Yong

机构信息

Department of Gastroenterology, Shandong Provincial Hospital of Shandong University, Jinan, PR China.

出版信息

Exp Toxicol Pathol. 2009 Sep;61(5):481-90. doi: 10.1016/j.etp.2008.07.007. Epub 2009 Jan 1.

Abstract

INTRODUCTION

Sepsis could be initiated by the gastrointestinal tract injury and subsequent bacterial translocation. In the present experiment, we aimed to investigate effect of ulinastatin (UTI) on the small intestinal injury and bacterial translocation in septic rats and role of mast cells degranulation in its action.

METHODS

Fifty-four male Wistar rats were randomly divided into three groups: sham laparatomy, cecal ligation and puncture (CLP), and CLP plus UTI. CLP was used to develop septic rat model and UTI was administered to rats intraperitoneally (50,000 U/kg) 30 min prior to CLP operation. After CLP or sham operation, variable parameters were investigated in three subsets of animals. One subset was used for measurements of nitrite and nitrate (NO(x)) concentration in plasma at 1, 6, 12, 18, and 24h and levels of NO(x) and iNOS mRNA in the small intestine, RMCP-II released into the small intestinal lumen, bacterial translocation and morphologic changes at 24h. The other subsets were used for the small intestinal motility and microvascular in vivo at 24h.

RESULTS

Bacterial translocation, barrier injury, impaired motility and blood flow, mast cells degranulation of the small intestine in the CLP group were found more severe than that in the sham group. Elevated RMCP-II, NO(x), and iNOS mRNA levels were also detected in the CLP group. Application of UTI not only protected the small intestine from sepsis but also diminished changes of intestinal mast cells.

CONCLUSION

UTI can significantly ameliorate the small intestinal injury and subsequent bacterial translocation by inhibiting mast cells degranulation in septic rats.

摘要

引言

脓毒症可能由胃肠道损伤及随后的细菌易位引发。在本实验中,我们旨在研究乌司他丁(UTI)对脓毒症大鼠小肠损伤和细菌易位的影响以及肥大细胞脱颗粒在其作用中的角色。

方法

54只雄性Wistar大鼠随机分为三组:假手术组、盲肠结扎穿孔(CLP)组和CLP加UTI组。采用CLP建立脓毒症大鼠模型,在CLP手术前30分钟给大鼠腹腔注射UTI(50,000 U/kg)。CLP或假手术后,在三组动物亚组中研究不同参数。一个亚组用于测量1、6、12、18和24小时血浆中亚硝酸盐和硝酸盐(NO(x))浓度以及24小时时小肠中NO(x)和iNOS mRNA水平、释放到小肠腔中的RMCP-II、细菌易位和形态学变化。其他亚组用于研究24小时时小肠的体内运动和微血管情况。

结果

发现CLP组小肠的细菌易位、屏障损伤、运动和血流受损、肥大细胞脱颗粒比假手术组更严重。CLP组还检测到RMCP-II、NO(x)和iNOS mRNA水平升高。应用UTI不仅保护小肠免受脓毒症影响,还减少了肠道肥大细胞的变化。

结论

UTI可通过抑制脓毒症大鼠肥大细胞脱颗粒显著改善小肠损伤及随后的细菌易位。

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