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Intestinal Mucus Layer Preservation in Female Rats Attenuates Gut Injury After Trauma-Hemorrhagic Shock

Sheth, Sharvil U. MD; Lu, Qi MD; Twelker, Kate BA; Sharpe, Susan M. MD; Qin, Xiaofa MD, PhD; Reino, Diego C. MD; Lee, Marlon A. MD; Xu, Da-Zhong MD, PhD; Deitch, Edwin A. MD

Journal of Trauma and Acute Care Surgery: February 2010 - Volume 68 - Issue 2 - p 279-288
doi: 10.1097/TA.0b013e3181caa6bd
Original Articles

Background: We tested the hypothesis that females are more resistant to trauma-hemorrhagic shock (T/HS)-induced gut injury than males, and this is related to better preservation of their intestinal mucus layer, which is influenced in turn by the estrus cycle stage at the time of injury.

Methods: Male, proestrus and diestrus female rats underwent a laparotomy (trauma) and 90 minutes of shock (∼35 mm Hg). At 3 hours after reperfusion, terminal ileum was harvested and stained with Carnoy's Alcian Blue for mucus assessment, hematoxylin and eosin, and periodic acid schiff for villous and goblet cell morphology and injury. Ileal permeability was measured in separate intestinal segments using the ex vivo everted gut sac technique.

Results: When compared with males, proestrus female rats were significantly more resistant to T/HS-induced morphologic gut injury, as reflected in both a lower incidence of villous injury (14% vs. 22%; p < 0.05) and a lesser grade of injury (1.0 vs. 2.8; p < 0.05) as well as preservation of gut barrier function (17.9 vs. 32.2; p < 0.05). This resistance to gut injury was associated with significant preservation of the mucus layer (87% vs. 62%; p < 0.05) and was influenced by the estrus cycle stage of the female rats. There was a significant inverse correlation between mucus layer coverage and the incidence (r 2 = 0.9; p < 0.0001) and magnitude (r 2 = 0.89; p < 0.0001) of villous injury and gut permeability (r 2 = 0.74; p < 0.001).

Conclusions: The resistance of female rats to T/HS-induced intestinal injury and dysfunction was associated with better preservation of the intestinal mucus barrier and was to some extent estrus cycle-dependent. Preservation of the mucus barrier may protect against shock-induced gut injury and subsequent distant organ injury by limiting the ability of luminal contents such as bacteria and digestive enzymes from coming into direct contact with the epithelium.

From the Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey.

Submitted for publication September 25, 2009.

Accepted for publication November 12, 2009.

Supported by NIH grants GM 59841 and T32 069330.

Presented at the 68th Annual Meeting of the American Association for the Surgery of Trauma, October 1–3, 2009, Pittsburgh, Pennsylvania.

Address for reprints: Edwin A. Deitch, MD, Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103; email:

© 2010 Lippincott Williams & Wilkins, Inc.