Heparin-binding EGF-like growth factor (HB-EGF) protects the intestines from radiation therapy-induced intestinal injury

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• 作者：Mika A.B. Matthews ; Daniel Watkins ; Am ; a Darbyshire ; William E. Carson ; Gail E. Besner
• 关键词：HB-EGF ; Radiation injury ; Intestines ; Proliferation ; Permeability
• 刊名：Journal of Pediatric Surgery
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：48
• 期：6
• 页码：1316-1322
• 全文大小：976 K

文摘

Purpose

Radiation therapy (RT) often induces enteritis by inhibiting proliferation and inducing apoptosis. Heparin-binding EGF-like growth factor (HB-EGF) has been shown to protect the intestine in several animal injury models. The objective of this study was to examine whether HB-EGF affects RT-induced intestinal injury.

Methods

HB-EGF or PBS was administered intraperitoneally to mice daily for 3 days, followed by total body irradiation (TBI). Three days after TBI, intestinal segments were harvested, and BrdU immunohistochemistry was performed to identify proliferating crypts (n = 25). Four days after TBI, intestinal segments were harvested and assessed for histologic injury (n = 34), and FITC-dextran was administered via gavage with serum FITC-dextran levels quantified to determine gut barrier function (n = 18).

Results

Compared to non-HB-EGF-treated irradiated mice, administration of HB-EGF to irradiated mice led to a significantly increased percentage of proliferative crypts (72.6 % vs. 50.5 % , p = 0.001), a significantly decreased percent of histologic sections with severe histologic injury (13.7 % vs. 20.3 % , p = 0.005), and significantly reduced intestinal permeability (18.8 ¦Ìg/mL vs. 22.6 ¦Ìg/mL, p = 0.02).

Conclusions

These results suggest that administration of HB-EGF protects the intestines from injury after exposure to radiation therapy. Administration of HB-EGF may represent a novel therapy for the prevention of radiation enteritis in the future.