Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats
Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats
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DOI：
10.1053/gast.1996.v110.pm8566596
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发表时间：
1996-02-01
期刊：
影响因子：
29.4
通讯作者：
Podolsky, DK
中科院分区：
文献类型：
--
作者：
Babyatsky, MW;deBeaumont, M;Podolsky, DK
背景与目的：三叶因子是一个在胃肠道粘膜细胞中大量表达的蛋白质家族，在体外具有保护上皮的作用。本研究旨在探讨三叶肽对大鼠胃粘膜损伤的保护作用。方法：采用无水乙醇（1.0mg/kg）灌胃或消炎痛（20 mg/kg）皮下注射造成大鼠胃粘膜损伤。分别于伤前、伤后不同时间点给予重组人解痉多肽（rHSP）或大鼠肠三叶因子（ITF）。溶剂或牛血清白蛋白用作对照。处死大鼠后测定胃内容物的pH值，肉眼和组织学盲法评价胃损伤。结果：口服rHSP和ITF对乙醇和消炎痛引起的胃粘膜损伤均有明显的保护作用（P < 0.005，剂量为1-15 mg/大鼠），在损伤前2小时给药;腹膜内rHSP对乙醇损伤没有保护作用，腹腔注射rHSP仅在给予最大剂量（15 mg）时才能防止吲哚美辛诱导的损伤。无论是rHSP还是ITF改变胃pH值，保护与三叶肽的全身吸收无关，结论：局部三叶肽保护胃粘膜免受乙醇和吲哚美辛诱导的胃损伤。这些肽有助于表面粘膜防御。
Background & Aims: The trefoil factors, a family of proteins abundantly expressed in gastrointestinal mucous cells, protect the epithelium in vitro. This study determines the effects of exogenously administered trefoil peptides on experimental injury in rats in vivo, Methods: Gastric injury was induced by either intragastric absolute ethanol (1.0 mt) or subcutaneous indomethacin (20 mg/kg). Recombinant human spasmolytic polypeptide (rHSP) or rat intestinal trefoil factor (ITF) were administered at different doses and time points before or after injury. Vehicle or bovine serum albumin was used as control. The pH of the stomach contents was assessed when the rats were killed, Gastric injury was blindly evaluated macroscopically and histologically. Serum levels of rHSP and ITF were determined by an enzyme-linked immunosorbent assay, Results: Oral rHSP and ITF markedly protected against both ethanol- and indomethacin-induced gastric injury (P < 0.005 at doses of 1-15 mg/rat) when given up to 2 hours before injury; no protection was noted by intraperitoneal rHSP against ethanol injury, Intraperitoneal rHSP protected against indomethacin-induced injury only at the maximal dose given (15 mg). Neither rHSP nor ITF altered gastric pH, Protection was not associated with systemic absorption of trefoil peptides, Conclusions: Topical trefoil peptides protect the gastric mucosa against ethanol- and indomethacin-induced gastric injuries. These peptides contribute to surface mucosal defense.