Effect of SQ 14225, an inhibitor of angiotensin I-converting enzyme, on the granulomatous response to Schistosoma mansoni eggs in mice.
Effect of SQ 14225, an inhibitor of angiotensin I-converting enzyme, on the granulomatous response to Schistosoma mansoni eggs in mice.
复制标题
血管紧张素 I 转换酶抑制剂 SQ 14225 对小鼠曼氏血吸虫卵肉芽肿反应的影响。
DOI：
10.1172/jci110142
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Gee,JB
中科院分区：
文献类型：
--
作者：
Weinstock,JV;Ehrinpreis,MN;Boros,DL;Gee,JB
鼠血吸虫病是一种与血清和肉芽肿血管紧张素 I 转换酶 (ACE) 活性高相关的肉芽肿性疾病。 SQ 14225 是一种 ACE 的特异性竞争性抑制剂，将其给予正常小鼠和感染曼氏血吸虫的小鼠，以确定该化合物是否可以抑制肉芽肿 ACE 活性并改变肉芽肿对血吸虫卵的反应大小。对具有峰值肉芽肿反应的感染小鼠口服 SQ 14225 5 周，可降低孤立肝脏肉芽肿中的 ACE 活性。接受治疗的小鼠表现出肝脏、结肠和回肠中肉芽肿大小的减小，并且分离的肝脏肉芽肿的羟脯氨酸浓度增加。相似剂量的 SQ 14225 可使正常小鼠和致敏小鼠体内血吸虫虫卵肺栓塞诱发的同步性肺肉芽肿的平均直径减小。对患有 2 周龄同步性肺肉芽肿的未致敏小鼠停药 SQ 14225 会导致炎症增加。接受 SQ 14225 的感染小鼠（而非正常小鼠）表现出门静脉压力、肝脏重量和体重降低。正常小鼠和感染小鼠均经历了体力生成、血管内容量扩大和血清 ACE 增加。这些观察结果表明，SQ 14225可以部分抑制血吸虫卵的肉芽肿反应和血吸虫病的病理表现。 ACE 可能在肉芽肿性炎症中具有炎症作用。
Murine schistosomiasis is a granulomatous disease associated with high serum and granuloma angiotensin I-converting enzyme (ACE) activity. SQ 14225, a specific competitive inhibitor of ACE, was administered to normal mice and mice infected with Schistosoma mansoni to determine whether this compound could inhibit granuloma ACE activity and modify the size of the granulomatous response to schistosome eggs. Peroral administration of SQ 14225 for 5 wk to infected mice with peak granulomatous responses decreased ACE activity in isolated liver granulomas. Treated mice demonstrated a decrease in granuloma size in the liver, colon, and ileum, and hydroxyproline concentration of isolated liver granulomas was increased. Mean diameters of synchronous pulmonary granulomas, induced by the pulmonary embolization of schistosome eggs into normal and sensitized mice, were decreased by a similar dose of SQ 14225. Withdrawal of SQ 14225 from unsensitized mice with 2-wk-old synchronous pulmonary granulomas induced an increase in inflammation. Infected, but not normal mice receiving SQ 14225 demonstrated reduced portal pressure, liver weight, and body weight. Both normal and infected mice experienced dipsogenesis, expanded intravascular volume, and increased serum ACE. These observations suggest that SQ 14225 can partially inhibit the granulomatous response to schistosome eggs and the pathological manifestations of schistosomiasis. It is possible that ACE has an inflammatory role in granulomatous inflammation.