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口服减毒沙门氏菌介导的肝细胞生长因子基因对大鼠 2,4,6-三硝基苯磺酸诱导溃疡性结肠炎的影响。

Effect of oral hepatocyte growth factor gene mediated by attenuated salmonella on 2-, 4-, 6-trinitro-benzene-sulfonic-acid-induced ulcerative colitis in rat.

机构信息

Medical Experiment Center, Lanzhou General Hospital of Lanzhou Military Region, People's Liberation Army, Key Laboratory of Stem Cell and Gene Drug in Gansu Province, Lanzhou, China.

出版信息

J Gastroenterol Hepatol. 2012 Mar;27(3):609-15. doi: 10.1111/j.1440-1746.2011.06894.x.

DOI:10.1111/j.1440-1746.2011.06894.x
PMID:21880069
Abstract

BACKGROUND AND AIM

In order to explore a new therapeutic method, we investigated the effects of exogenously expressed hepatocyte growth factor mediated by attenuated salmonella (TPH) on rats with ulcerative colitis (UC) induced by 2-, 4-, 6-trinitro-benzene-sulfonic acid.

METHODS

The UC rats were treated with TPH, attenuated salmonella with a eukaryotic expression vector (TP) or sodium bicarbonate (model control [MC]) every other day. Cluster of differentiation (CD)4(+) and CD8(+) T cells and immunoglobulins in the blood were analyzed by flow cytometry. The HGF expression was determined by immunohistochemistry. A macroscopic-scale observation of the colon and a histological assessment were also carried out.

RESULTS

The CD4(+) T counts and the CD4(+) /CD8(+) ratio in the TPH group were significantly lower than that in the MC group. The immunoglobulin M and immunoglobulin G(1) levels in the TPH group were significantly lower than that in the MC group and TP group. After treatment with TPH, the symptoms of the ulcerative rats were significantly alleviated. The colonic lesion grades in the TPH group were lower than that in the TP group and MC group. Significant improvement occurred after the TPH treatment, as evidenced by alleviated mucosal inflammation. At 7 days post-treatment, the HGF expression in the colonic tissues that were treated with TPH was stronger than that in the samples treated with TP.

CONCLUSIONS

TPH inhibits the proliferation of T lymphocytes and the antibody production of B lymphocytes. Furthermore, it ameliorates mucosal inflammation and promotes the regeneration of mucosa and the healing of the colonic ulceration.

摘要

背景与目的

为了探索新的治疗方法,我们研究了经减毒鼠伤寒沙门氏菌(TPH)转染的肝细胞生长因子(HGF)对 2,4,6-三硝基苯磺酸诱导的溃疡性结肠炎(UC)大鼠的作用。

方法

用 TPH、携带真核表达载体的减毒鼠伤寒沙门氏菌(TP)或碳酸氢钠(模型对照组[MC])每隔一天治疗 UC 大鼠。采用流式细胞术分析血液中的 CD4+和 CD8+T 细胞和免疫球蛋白。用免疫组织化学法检测 HGF 表达。对结肠进行宏观观察和组织学评估。

结果

TPH 组 CD4+T 计数和 CD4+/CD8+比值明显低于 MC 组。TPH 组免疫球蛋白 M 和免疫球蛋白 G1 水平明显低于 MC 组和 TP 组。TPH 治疗后,溃疡性大鼠的症状明显缓解。TPH 组结肠病变程度低于 TP 组和 MC 组。TPH 治疗后明显改善,黏膜炎症减轻。治疗后 7 天,TPH 处理的结肠组织中 HGF 的表达强于 TP 处理的样本。

结论

TPH 抑制 T 淋巴细胞增殖和 B 淋巴细胞抗体产生。此外,它还可改善黏膜炎症,促进黏膜再生和结肠溃疡愈合。

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Effect of oral hepatocyte growth factor gene mediated by attenuated salmonella on 2-, 4-, 6-trinitro-benzene-sulfonic-acid-induced ulcerative colitis in rat.口服减毒沙门氏菌介导的肝细胞生长因子基因对大鼠 2,4,6-三硝基苯磺酸诱导溃疡性结肠炎的影响。
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