Department of Anaesthesia, Ernst-Moritz-Arndt-Universität Greifswald, Fr. -Loeffler Str. 23B, Greifswald 17489, Germany.
Microvasc Res. 2011 Nov;82(3):397-403. doi: 10.1016/j.mvr.2011.06.010. Epub 2011 Jul 8.
Intestinal barrier dysfunction plays an important role in sepsis. Females may tolerate sepsis better than males, which could be due to the relative resistance of the female intestine to gut injury and inflammation when subjected to sepsis. In this study the intestinal microcirculation was investigated in 50 female and 40 male rats divided in to 9 groups of 10 animals. Male and female rats were subjected to sham CASP (colon ascendens stent peritonitis). We induced experimental sepsis (CASP) in another two groups of male and female rats. The role of the estradiol treatment was evaluated both in male and ovariectomized female rats. Female rats were subjected to sham ovariectomy 3 weeks before sham CASP. Male and ovariectomized female rats were treated with estradiol (10mg/kg estradiol in rizinus oil immediately and 12h following CASP). Another two groups of male and ovariectomized female rats received placebo oil treatment. To evaluate the effects of gender and estradiol treatment on the microvascular perfusion during sepsis, intravital microscopy was performed twenty-four hours after sham CASP or CASP surgery, which permits the in vivo determination of leukocyte-endothelial cell interaction (rolling leukocytes and adherent leukocytes) and the measurement of functional capillary density (FCD), which served as the measure of quality of microvascular perfusion. We found that there was gender difference mainly in the leukocyte endothelial interaction rather than the functional capillary density (FCD), in which male showed significant increases (P<0.05) both in the leukocyte adhesion and rolling leukocytes in submucosal venules (V1 and V3) in comparison to female rats. (Leukocyte adhesion: V1 107.1 ± 49.2n/mm(2); V3 112.3 ± 68.1n/mm(2)) (Rolling leukocytes:V1 16.2 ± 10.3n/min; V3 8.4 ± 8.2n/min). In addition estradiol replacement in ovariectomized female and male rats induced significant decreases (P<0.05) in the leukocyte adhesion and rolling (V1 and V3) with a significant increase in the muscular FCD in comparison to the corresponding placebo treated groups. (Leukocyte adhesion: V1 60 ± 31 n/mm(2); V3 78.11 ± 37.6n/mm(2)) (Rolling leukocytes: V1 13.4 ± 8.9 n/min; V3 5.8 ± 7.4n/min) (Longitudinal muscular FCD (cm/cm(2)): in ovariectomized female rats 107.1 ± 12.2; in male rats 106.2 ± 15.3) (Circular muscular FCD (cm/cm(2)): in ovariectomized female rats: 84.8 ± 14.2; in male rats: 86.1 ± 15.3). We conclude that gender difference in the leukocyte endothelial interaction could explain the resistance of female intestine to injury, and that estradiol treatment could improve the intestinal microcirculation through its effects on the leukocyte endothelial interaction and the FCD both in male and ovariectomized female rats.
肠道屏障功能障碍在脓毒症中起重要作用。女性可能比男性更能耐受脓毒症，这可能是由于女性肠道在受到脓毒症侵袭时，相对于男性肠道，其对肠道损伤和炎症的抵抗力更强。在这项研究中，我们研究了 50 只雌性和 40 只雄性大鼠的肠道微循环，这些大鼠分为 9 组，每组 10 只动物。雄性和雌性大鼠均接受假 CASP（升结肠支架性腹膜炎）。我们在另外两组雄性和雌性大鼠中诱导了实验性脓毒症（CASP）。我们评估了雌二醇治疗在雄性和卵巢切除的雌性大鼠中的作用。雌性大鼠在接受假 CASP 前 3 周接受假卵巢切除术。雄性和卵巢切除的雌性大鼠立即用 10mg/kg 雌二醇在蓖麻油中治疗，并在 CASP 后 12 小时再次治疗。另外两组雄性和卵巢切除的雌性大鼠接受安慰剂油治疗。为了评估性别和雌二醇治疗对脓毒症期间微血管灌注的影响，在假 CASP 或 CASP 手术后 24 小时进行活体显微镜检查，这允许在体内确定白细胞-内皮细胞相互作用（滚动白细胞和黏附白细胞）和功能性毛细血管密度（FCD）的测量，FCD 作为微血管灌注质量的测量。我们发现，主要是白细胞-内皮细胞相互作用存在性别差异，而功能性毛细血管密度（FCD）则不然，与雌性大鼠相比，雄性大鼠在黏膜下小静脉（V1 和 V3）中的白细胞黏附和滚动白细胞均显著增加（P<0.05）。（白细胞黏附：V1 107.1 ± 49.2n/mm²；V3 112.3 ± 68.1n/mm²）（滚动白细胞：V1 16.2 ± 10.3n/min；V3 8.4 ± 8.2n/min）。此外，在卵巢切除的雌性和雄性大鼠中，雌二醇替代治疗可显著降低（P<0.05）白细胞黏附和滚动（V1 和 V3），并显著增加相应的安慰剂治疗组的肌性 FCD。（白细胞黏附：V1 60 ± 31 n/mm²；V3 78.11 ± 37.6n/mm²）（滚动白细胞：V1 13.4 ± 8.9 n/min；V3 5.8 ± 7.4n/min）（纵向肌性 FCD（cm/cm²）：在卵巢切除的雌性大鼠中为 107.1 ± 12.2；在雄性大鼠中为 106.2 ± 15.3）（环形肌性 FCD（cm/cm²）：在卵巢切除的雌性大鼠中为 84.8 ± 14.2；在雄性大鼠中为 86.1 ± 15.3）。我们得出结论，白细胞-内皮细胞相互作用的性别差异可以解释女性肠道对损伤的抵抗力，而雌二醇治疗可以通过其对白细胞-内皮细胞相互作用和 FCD 的影响，改善雄性和卵巢切除的雌性大鼠的肠道微循环。
