Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Transplantation. 2022 Feb 1;106(2):337-347. doi: 10.1097/TP.0000000000003705.
Hepatic estrogen signaling, which is important in liver injury/recovery, is determined by the level of systemic estrogen and hepatic estrogen receptor. We aimed to evaluate whether females' advantage in the tolerance of hepatic ischemia-reperfusion injury decreases according to the age of 40 y (systemic estrogen decrease) and macrosteatosis (hepatic estrogen receptor decrease).
We included 358 living liver donors (128 female and 230 male individuals). The tolerance of hepatic ischemia-reperfusion injury was determined by the slope of the linear regression line modeling the relationship between the duration of intraoperative hepatic ischemia and the peak postoperative transaminase level. Estrogen receptor content was measured in the biopsied liver samples using immunohistochemistry.
In the whole cohort, the regression slope for aspartate transaminase was comparable between female and male individuals (P = 0.940). Within the subgroup of donors aged ≤40 y, the regression slope was significantly smaller in female individuals (P = 0.031), whereas it was comparable within donors aged >40 y (P = 0.867). Within the subgroup of nonmacrosteatotic donors aged ≤40 y, the regression slope was significantly smaller in female individuals in univariable (P = 0.002) and multivariable analysis (P = 0.006), whereas the sex difference was not found within macrosteatotic donors aged ≤40 y (P = 0.685). Estrogen receptor content was significantly greater in female individuals within nonmacrosteatotic donors aged ≤40 y (P = 0.021), whereas it was not different in others of age >40 y or with macrosteatosis (P = 0.450).
The tolerance of hepatic ischemia-reperfusion injury was greater in female individuals than in male individuals only when they were <40 y and without macrosteatosis. The results were in agreement with the hepatic estrogen receptor immunohistochemistry study.
肝脏雌激素信号在肝脏损伤/恢复中很重要，由全身雌激素水平和肝脏雌激素受体决定。我们旨在评估女性在肝脏缺血再灌注损伤耐受性方面的优势是否会随着 40 岁（全身雌激素下降）和脂肪变性（肝脏雌激素受体下降）而降低。
我们纳入了 358 名活体肝供体（女性 128 例，男性 230 例）。肝脏缺血再灌注损伤的耐受性通过建立术中肝缺血时间与术后转氨酶峰值之间线性回归关系的线性回归斜率来确定。使用免疫组织化学方法测量活检肝组织中的雌激素受体含量。
在整个队列中，女性和男性个体的天冬氨酸转氨酶回归斜率无差异（P = 0.940）。在≤40 岁供体亚组中，女性个体的回归斜率明显较小（P = 0.031），而在>40 岁供体中无差异（P = 0.867）。在≤40 岁非脂肪变性供体亚组中，女性个体的回归斜率在单变量（P = 0.002）和多变量分析（P = 0.006）中明显较小，而在≤40 岁脂肪变性供体中则无性别差异（P = 0.685）。在≤40 岁非脂肪变性供体中，女性个体的雌激素受体含量明显较高（P = 0.021），而在>40 岁或有脂肪变性的供体中则无差异（P = 0.450）。
只有当女性个体<40 岁且无脂肪变性时，她们的肝脏缺血再灌注损伤耐受性才大于男性个体。结果与肝脏雌激素受体免疫组织化学研究一致。
