Sheth Sharvil U, Lu Qi, Twelker Kate, Sharpe Susan M, Qin Xiaofa, Reino Diego C, Lee Marlon A, Xu Da-Zhong, Deitch Edwin A
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
J Trauma. 2010 Feb;68(2):279-88. doi: 10.1097/TA.0b013e3181caa6bd.
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.
Male, proestrus and diestrus female rats underwent a laparotomy (trauma) and 90 minutes of shock ( approximately 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.
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 = 0.9; p < 0.0001) and magnitude (r = 0.89; p < 0.0001) of villous injury and gut permeability (r = 0.74; p < 0.001).
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.
我们验证了以下假说,即雌性比雄性更能抵抗创伤性失血性休克(T/HS)诱导的肠道损伤,这与它们肠道黏液层得到更好的保护有关,而肠道黏液层又受损伤时发情周期阶段的影响。
对雄性、动情前期和动情后期的雌性大鼠进行剖腹手术(创伤)并使其休克90分钟(约35毫米汞柱)。再灌注3小时后,采集回肠末端,用卡诺氏阿尔辛蓝染色以评估黏液,用苏木精和伊红染色,并用高碘酸希夫染色以观察绒毛和杯状细胞形态及损伤情况。使用离体外翻肠囊技术在单独的肠段中测量回肠通透性。
与雄性相比,动情前期雌性大鼠对T/HS诱导的肠道形态损伤具有显著更强的抵抗力,这体现在绒毛损伤发生率较低(14%对22%;p<0.05)、损伤程度较轻(1.0对2.8;p<0.05)以及肠道屏障功能得到保留(17.9对32.2;p<0.05)。这种对肠道损伤的抵抗力与黏液层的显著保留有关(87%对62%;p<0.05),并且受雌性大鼠发情周期阶段的影响。黏液层覆盖度与绒毛损伤的发生率(r = 0.9;p<0.0001)和程度(r = 0.89;p<0.0001)以及肠道通透性(r = 0.74;p<0.001)之间存在显著负相关。
雌性大鼠对T/HS诱导的肠道损伤和功能障碍的抵抗力与肠道黏液屏障得到更好的保护有关,并且在一定程度上依赖于发情周期。黏液屏障的保留可能通过限制细菌和消化酶等管腔内容物与上皮直接接触的能力,来预防休克诱导的肠道损伤及随后的远处器官损伤。