Babyatsky M W, deBeaumont M, Thim L, Podolsky D K
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Gastroenterology. 1996 Feb;110(2):489-97. doi: 10.1053/gast.1996.v110.pm8566596.
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.
Gastric injury was induced by either intragastric absolute ethanol (1.0 mL) 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.
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.
Topical trefoil peptides protect the gastric mucosa against ethanol- and indomethacin-induced gastric injuries. These peptides contribute to surface mucosal defense.
三叶因子是一类在胃肠道黏液细胞中大量表达的蛋白质家族，在体外可保护上皮细胞。本研究旨在确定外源性给予三叶肽对大鼠体内实验性损伤的影响。
通过胃内给予无水乙醇（1.0 mL）或皮下注射吲哚美辛（20 mg/kg）诱导胃损伤。在损伤前后的不同剂量和时间点给予重组人解痉多肽（rHSP）或大鼠肠三叶因子（ITF）。以赋形剂或牛血清白蛋白作为对照。处死大鼠时评估胃内容物的pH值。对胃损伤进行宏观和组织学的盲法评估。采用酶联免疫吸附测定法测定血清中rHSP和ITF的水平。
在损伤前2小时内给予口服rHSP和ITF，对乙醇和吲哚美辛诱导的胃损伤均有显著保护作用（剂量为1 - 15 mg/大鼠时，P < 0.005）；腹腔注射rHSP对乙醇损伤无保护作用。腹腔注射rHSP仅在最大剂量（15 mg）时对吲哚美辛诱导的损伤有保护作用。rHSP和ITF均未改变胃的pH值。保护作用与三叶肽的全身吸收无关。
局部应用三叶肽可保护胃黏膜免受乙醇和吲哚美辛诱导的胃损伤。这些肽有助于表面黏膜防御。
