Salmenkari Hanne, Issakainen Tomi, Vapaatalo Heikki, Korpela Riitta
Hanne Salmenkari, Tomi Issakainen, Heikki Vapaatalo, Riitta Korpela, Faculty of Medicine, Pharmacology, University of Helsinki, 00290 Helsinki, Finland.
World J Gastroenterol. 2015 Sep 21;21(35):10072-9. doi: 10.3748/wjg.v21.i35.10072.
To investigate local corticosterone production and angiotensin-I converting enzyme (ACE) protein expression and their interaction in healthy and inflamed intestine.
Acute intestinal inflammation was induced to six weeks old male Balb/c mice by administration of either 3% or 5% dextran sodium sulfate (DSS) in drinking water for 7 d (n = 12 in each group). Healthy controls (n = 12) were given tap water. Corticosterone production and ACE protein shedding were measured from ex vivo incubates of the small and large intestine using EIA and ELISA, respectively. Morphological changes of the intestinal wall were assessed in hematoxylin-eosin stained tissue preparations of jejunum and distal colon. Effects of angiotensin II, captopril and metyrapone on corticosterone production was assessed by incubating pieces of small intestine of healthy mice in the presence of 0.1, 1 or 10 μmol/L angiotensin II, 1, 10 or 100 μmol/L captopril or 1, 10 or 100 μmol/L metyrapone solutions and measuring corticosterone released to the incubation buffer after 90 min (n = 5 in each group).
Both concentrations of DSS induced inflammation and morphological changes in large intestines but not in small intestines. Changes were observed as distortions of the crypt structure, mucosal erosion, immune cell infiltration to the mucosa and submucosal edema. Ex vivo corticosterone production (2.9 ± 1.0 ng/mL vs 2.0 ± 0.8 ng/mL, P = 0.034) and ACE shedding (269.2 ± 97.1 ng/mL vs 175.7 ± 52.2 ng/mL, P = 0.016) were increased in small intestines in 3% DSS group compared to the controls. In large intestine, corticosterone production was increased compared to the controls in both 3% DSS (229 ± 81 pg/mL vs 158 ± 30 pg/mL, P = 0.017) and 5% DSS groups (366 ± 163 pg/mL vs 158 ± 30 pg/mL, P = 0.002). Large intestine ACE shedding was increased in 5% DSS group (41.5 ± 9.0 ng/mL vs 20.9 ± 5.2 ng/mL, P = 0.034). Angiotensin II treatment augmented corticosterone production in small intestine at concentration of 10 μmol/L (0.97 ± 0.21 ng/mg protein vs 0.40 ± 0.09 ng/mg protein, P = 0.036).
Intestinal ACE shedding is increased by DSS-induced intestinal inflammation and parallels local corticosterone production. ACE product angiotensin II stimulates corticosterone formation in healthy intestine.
研究健康和炎症肠道中局部皮质酮的产生、血管紧张素-I转换酶（ACE）蛋白表达及其相互作用。
通过在六周龄雄性Balb/c小鼠饮用水中给予3%或5%的葡聚糖硫酸钠（DSS）7天来诱导急性肠道炎症（每组n = 12）。健康对照组（n = 12）给予自来水。分别使用酶免疫分析（EIA）和酶联免疫吸附测定（ELISA）从小肠和大肠的体外孵育物中测量皮质酮的产生和ACE蛋白的释放。在苏木精-伊红染色的空肠和远端结肠组织切片中评估肠壁的形态学变化。通过在含有0.1、1或10 μmol/L血管紧张素II、1、10或100 μmol/L卡托普利或1、10或100 μmol/L美替拉酮溶液的条件下孵育健康小鼠的小肠片段，并在90分钟后测量释放到孵育缓冲液中的皮质酮，来评估血管紧张素II、卡托普利和美替拉酮对皮质酮产生的影响（每组n = 5）。
两种浓度的DSS均诱导大肠炎症和形态学变化，但小肠未出现。观察到的变化包括隐窝结构扭曲、黏膜糜烂、免疫细胞浸润至黏膜以及黏膜下水肿。与对照组相比，3%DSS组小肠的体外皮质酮产生（2.9±1.0 ng/mL对2.0±0.8 ng/mL，P = 0.034）和ACE释放（269.2±97.1 ng/mL对175.7±52.2 ng/mL，P = 0.016）增加。在大肠中，3%DSS组（229±81 pg/mL对158±
