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谷氨酰胺通过靶向脓毒症大鼠的NF-κB信号通路对肠道组织起保护作用。

Glutamine has a protective role on intestinal tissues via targeting NF-κB pathway in rats with sepsis.

作者信息

Wu T-Y, Zhang H-B

机构信息

Department of Critical Care Medicine, Haijiya Hospital, Shanxian County, Heze, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):184-191. doi: 10.26355/eurrev_201908_18646.

DOI:10.26355/eurrev_201908_18646
PMID:31389590
Abstract

OBJECTIVE

To study the protective effect of glutamine on the intestinal tissues of septic rats by regulating the nuclear factor-κB (NF-κB) pathway.

MATERIALS AND METHODS

A total of 30 rats were divided into the Sham group, Model group, and Glutamine group using a random number table. The changes in the intestinal tissues in rats were observed via hematoxylin-eosin (HE) staining, and the difference in the content of serum inflammatory factor tumor necrosis factor-α (TNF-α) was detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the apoptosis of the intestinal tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the protein expression of NF-κB in intestinal tissues was detected via Western blotting.

RESULTS

In the Sham group, the rats had normal activity and good mental state, and there were no evident lesions in the abdominal cavity. Compared with the rats in the Sham group, the rats in the Model group had very poor mental state and erected hair, and they trembled and barely moved. After the abdomen was opened, there were bad smell and evident bleeding in the abdominal cavity, and the cecum became black with adhesion and swelling. In the Glutamine group, the symptoms were significantly alleviated compared with the Model group. The morphological observation of the intestinal tissues revealed that in the Sham group, the intestinal villi were regularly and clearly arranged, and there was no congestion in the capillaries. Compared with the Sham group, the intestinal villi were disorderly arranged with rupture in the Model group, and the severe capillary congestion was clearly visible and accompanied by ulcer. In the Glutamine group, the intestinal villi had normal morphology and regular arrangement after treatment, the subepithelial space was significantly dilated, the capillary dilation and the congestion could be seen and the lamina propria was intact. In the Sham group, the pathological score was 0 point, and the intestinal mucosa and villi had normal structure. Compared with that in the Sham group, the pathological score of the intestinal tissues were significantly increased in the Model group (p<0.05). In the Glutamine group, the pathological score significantly declined after treatment compared with that in the Model group (p<0.05). Besides, the content of the inflammatory factor TNF-α in the intestinal tissues was the highest in the Model group (p<0.05), and it was lower in the Glutamine group than that in the Sham group (p<0.05), indicating that glutamine can effectively reduce the content of the inflammatory factor TNF-α, exerting a certain protective effect on the intestinal tissues. The number of apoptotic intestinal epithelial cells was remarkably increased in the Model group compared with that in the Sham group (p<0.05), and it was remarkably decreased in the Glutamine group compared with that in the Model group (p<0.05). The Model group had a significantly higher protein expression of NF-κB in intestinal tissues than in the Sham group and Glutamine group (p<0.05), Sham group had the lowest protein expression of NF-κB in intestinal tissues (p<0.05), and the Glutamine group had a significantly lower protein expression of NF-κB in intestinal tissues than the Model group (p<0.05).

CONCLUSIONS

Glutamine inhibits the protein expression of NF-κB, thereby exerting a protective effect on intestinal tissues of sepsis rats.

摘要

目的

通过调节核因子-κB(NF-κB)通路,研究谷氨酰胺对脓毒症大鼠肠道组织的保护作用。

材料与方法

采用随机数字表法将30只大鼠分为假手术组、模型组和谷氨酰胺组。通过苏木精-伊红(HE)染色观察大鼠肠道组织的变化,采用酶联免疫吸附测定(ELISA)法检测血清炎症因子肿瘤坏死因子-α(TNF-α)含量的差异。此外,通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测肠道组织的凋亡情况,采用蛋白质印迹法检测肠道组织中NF-κB的蛋白表达。

结果

假手术组大鼠活动正常,精神状态良好,腹腔内无明显病变。与假手术组大鼠相比,模型组大鼠精神状态极差,毛发竖起,颤抖且几乎不动。打开腹腔后,腹腔内有恶臭和明显出血,盲肠变黑,伴有粘连和肿胀。谷氨酰胺组大鼠的症状与模型组相比明显减轻。肠道组织的形态学观察显示,假手术组肠道绒毛排列规则、清晰,毛细血管无充血。与假手术组相比,模型组肠道绒毛排列紊乱且有断裂,可见严重的毛细血管充血并伴有溃疡。谷氨酰胺组治疗后肠道绒毛形态正常,排列规则,上皮下间隙明显增宽,可见毛细血管扩张和充血,固有层完整。假手术组病理评分为0分,肠黏膜和绒毛结构正常。与假手术组相比,模型组肠道组织的病理评分显著升高(p<0.05)。谷氨酰胺组治疗后病理评分与模型组相比显著下降(p<0.05)。此外,肠道组织中炎症因子TNF-α的含量在模型组最高(p<0.05),在谷氨酰胺组低于假手术组(p<0.05),表明谷氨酰胺可有效降低炎症因子TNF-α的含量,对肠道组织发挥一定的保护作用。与假手术组相比,模型组凋亡肠上皮细胞数量显著增加(p<0.05),与模型组相比,谷氨酰胺组凋亡肠上皮细胞数量显著减少(p<0.05)。模型组肠道组织中NF-κB的蛋白表达显著高于假手术组和谷氨酰胺组(p<0.05),假手术组肠道组织中NF-κB的蛋白表达最低(p<0.05),谷氨酰胺组肠道组织中NF-κB的蛋白表达显著低于模型组(p<0.05)。

结论

谷氨酰胺抑制NF-κB的蛋白表达,从而对脓毒症大鼠的肠道组织发挥保护作用。

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