Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
Department of Pediatric Surgery, "V Buzzi" Children's Hospital, University of Milan, Milan, Italy.
Congenit Anom (Kyoto). 2022 May;62(3):105-112. doi: 10.1111/cga.12462. Epub 2022 Feb 25.
To date, fetal liver implication is not a well-understood phenomenon in congenital diaphragmatic hernia (CDH). We evaluated the fetal morphologic changes on liver growth after surgical procedure in CDH experimental model. A diaphragmatic defect at gestational day E25 and tracheal occlusion (TO) at E27 were surgically created in rabbit fetuses. Five experimental groups were assessed: control group, left CDH, right CDH, CDH + TO, and TO alone. Body and organ growth were measured. For histological evaluation of the CDH effect, liver sections were collected. Left-CDH group had livers with increased leukocyte infiltration in comparison with controls (p = 0.02). Increased capillary sinusoid congestion and hepatocyte vacuolation were greater in left-CDH compared with the right-CDH group (p = 0.05). Capillary sinusoid congestion and interstitial edema were more evident in the left-CDH compared with CDH + TO group (p = 0.05). Increases in sinusoid congestion, hepatocyte vacuolation, and interstitial edema were also greater in the CDH + TO compared with controls (p ≤ 0.02). Intrathoracic liver weight was higher in right-CDH compared with left-CDH group (p < 0.001). Total lung weights (TLW) were significantly lower in both left-CDH compared with controls (p < 0.001), CDH + TO (p = 0.01), and TO (p < 0.01) and in right-CDH compared with CDH + TO (p < 0.01) and TO (p < 0.01). Decreased kidney and heart weights were also recorded. Hemodynamics and structural fetal liver changes in laterality were noted in CDH model. Regulation of intrathoracic liver weights seems to be disturbed by the absence of diaphragmic contact. Pulmonary injury is supported by the effect of a first hit, while the growth of internal organs suggests a multisystemic remodeling related to the fetal adaptation.
迄今为止,胎儿肝脏在先天性膈疝 (CDH) 中的作用尚不清楚。我们评估了 CDH 实验模型中手术治疗后肝脏生长的胎儿形态变化。在兔胎儿中,于妊娠第 25 天建立膈疝缺陷,第 27 天进行气管阻塞 (TO)。评估了五个实验组:对照组、左侧 CDH、右侧 CDH、CDH+TO 和单独 TO。测量了身体和器官的生长。为了评估 CDH 对肝脏的影响,收集了肝脏切片。与对照组相比,左侧 CDH 组的肝脏白细胞浸润增加(p=0.02)。与右侧 CDH 组相比,左侧 CDH 组的毛细血管窦充血和肝细胞空泡化更明显(p=0.05)。与 CDH+TO 组相比,左侧 CDH 组的毛细血管窦充血和间质水肿更为明显(p=0.05)。与对照组相比,CDH+TO 组的窦充血、肝细胞空泡化和间质水肿增加更为明显(p≤0.02)。右侧 CDH 组的胸腔内肝重高于左侧 CDH 组(p<0.001)。与对照组相比,左 CDH 组(p<0.001)、CDH+TO 组(p=0.01)和 TO 组(p<0.01)以及右 CDH 组(p<0.01)和 TO 组(p<0.01)的总肺重(TLW)显著降低。还记录了肾脏和心脏重量的减少。在 CDH 模型中观察到侧支肝血液动力学和结构变化。胸腔内肝重的调节似乎因膈膜接触缺失而受到干扰。肺损伤支持首次打击的作用,而内部器官的生长表明与胎儿适应相关的多系统重塑。