科研之友
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摘要
Stress-induced gastric ulcer is an important life-threatening condition, while the molecular basis of its development is incompletely understood. Toll-like receptor 4 (TLR4), an innate immune pattern recognition receptor, can induce pro-inflammatory transcription, aggravating a stress ulcer. The present study found that TLR4 played a protective role in a mouse model of water immersion (23 degrees C) restraint stress. Wild-type (WT) and TLR4(-/-) male mice were respectively divided into five groups (5 per group), and exposed to the stressor for 0, 0.5, 1, 2, or 4hours. Gastric ulcer index, determined post mortem, increased with time in both types of mice but was greater in TLR4(-/-) mice. Furthermore, increased serum cortisol and corticosterone concentrations were observed in WT mice only, and such increases were detected only in WT mice 4h after lipopolysaccharide (LPS) treatment (2mg/kg, intraperitoneal injection). Moreover, the administration of cortisol alleviated the gastric injury in TLR4(-/-) mice. Western blotting showed expression in the adrenal of P450scc (CYP11A1), the first rate-limiting enzyme in the synthesis of steroids, was increased 4h after water immersion restraint stress or LPS treatment in WT mice, but was conversely decreased in TLR4(-/-) mice after either stressor. Furthermore, in adrenal glands of TLR4(-/-) mice, structural distortion of mitochondria (which contain CYP11A1) was found with electron microscopy, and lack of lipid-storing droplets was found using light microscopy on adrenal cryosections stained with Oil red O. These data indicate that TLR4 plays a protective role in stress-induced gastric ulcer that is exerted via impacting synthesis of glucocorticoid in the adrenal gland.
- 出版日期2017
- 单位南京中医药大学; 中国人民解放军第二军医大学; 上海交通大学
