人解痉多肽是一种刺激细胞迁移的细胞保护剂。
Human spasmolytic polypeptide is a cytoprotective agent that stimulates cell migration.
作者信息
Playford R J, Marchbank T, Chinery R, Evison R, Pignatelli M, Boulton R A, Thim L, Hanby A M
机构信息
Department of Gastroenterology, Royal Postgraduate Medical School, London, England.
出版信息
Gastroenterology. 1995 Jan;108(1):108-16. doi: 10.1016/0016-5085(95)90014-4.
BACKGROUND/AIMS: Gastric epithelium is attacked by acid, pepsin, and ingested agents. When a mucosal lesion occurs, the defect is rapidly closed by cell migration. Because spasmolytic polypeptide is rapidly produced at sites of injury, we postulated that human spasmolytic polypeptide (hSP) was important in mucosal repair. Recombinant hSP was used to test this hypothesis.
METHODS
The ulcer healing effect of various doses of hSP administered orally and subcutaneously was examined using an indomethacin (20 mg/kg) restraint rat model of gastric damage. Stability of hSP in gastrointestinal juice was determined using size-exclusion chromatography. The effect of hSP on migration of human colonic carcinoma cell lines HT29 and SW480 was determined using collagen gel invasion and wounded monolayer assays. Proliferation was assessed using [3H]thymidine incorporation and toluidine blue staining.
RESULTS
Infusions of hSP at 25 and 50 micrograms.kg-1.h-1 subcutaneously decreased gastric damage by about 50% (P < 0.01) without changing acid secretion. Oral hSP was ineffective. hSP was stable in gastrointestinal juice. hSP stimulated migration of HT29 cells but did not affect proliferation and had no effect on SW480 cells.
CONCLUSIONS
hSP may play a key role in the early stages of mucosal repair by stimulating the initial re-epithelialization by cell migration.
背景/目的：胃上皮受到酸、胃蛋白酶和摄入物质的攻击。当黏膜损伤发生时，缺损会通过细胞迁移迅速闭合。由于解痉多肽在损伤部位迅速产生，我们推测人解痉多肽（hSP）在黏膜修复中起重要作用。使用重组hSP来验证这一假设。
方法
使用吲哚美辛（20mg/kg）束缚大鼠胃损伤模型，检测口服和皮下给予不同剂量hSP后的溃疡愈合效果。使用尺寸排阻色谱法测定hSP在胃肠液中的稳定性。使用胶原凝胶侵袭试验和单层划痕试验测定hSP对人结肠癌细胞系HT29和SW480迁移的影响。使用[3H]胸腺嘧啶核苷掺入法和甲苯胺蓝染色评估细胞增殖。
结果
皮下注射25和50μg·kg-1·h-1的hSP可使胃损伤减少约50%（P<0.01），而不改变胃酸分泌。口服hSP无效。hSP在胃肠液中稳定。hSP刺激HT29细胞迁移，但不影响其增殖，对SW480细胞无影响。
结论
hSP可能通过刺激细胞迁移引起的初始再上皮化，在黏膜修复的早期阶段起关键作用。
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