Liao Junzuo, Liu Wenying, Zhang Libin, Li Qin, Hou Fang, Zou Pingjin
Department of Pediatric Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China Chengdu, Sichuan, China.
Institute of Laboratory Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Chengdu, Sichuan, China.
Int J Clin Exp Pathol. 2020 Jan 1;13(1):81-88. eCollection 2020.
The aim of this study was to investigate the therapeutic effects and underlying mechanism of tetramethylpyrazine (TMP) on lung development using a rat model of congenital diaphragmatic hernia (CDH). Nitrofen was used to induce CDH. Pregnant rats were divided into three groups: control, CDH, and CDH+TMP. In the CDH and CDH+TMP, fetuses only with left diaphragmatic hernias were chosen for analysis. Lung and body weight were recorded and lung histologic evaluations, image analysis, and western blot analysis of YAP, p-YAP and LATS1 were performed after lung processing. A markedly abnormal structure was observed, as evidenced by pulmonary hypoplasia and vascular remodeling, in the CHD. These abnormalities were improved in the CDH+TMP. There were significant differences between the CHD and CHD+TMP in percentage of medial wall thickness, arteriole muscularization, radial alveolar counts, AA%, and alveolar septal thickness. YAP expression was markedly increased in the CHD compared to the controls, which was not affected by antenatal TMP administration. However, prenatal TMP intervention significantly increased expression of LATS1 and phosphorylation of YAP in the CDH fetuses. Our results demonstrate that antenatal TMP administration improved vascular remodeling and promoted lung development in a rat model of CHD, potentially through increasing expression of LATS1 and phosphorylation of YAP.
本研究旨在利用先天性膈疝（CDH）大鼠模型探讨川芎嗪（TMP）对肺发育的治疗作用及潜在机制。使用硝呋太尔诱导CDH。将怀孕大鼠分为三组：对照组、CDH组和CDH+TMP组。在CDH组和CDH+TMP组中，仅选择患有左侧膈疝的胎儿进行分析。记录肺和体重，并在肺处理后进行肺组织学评估、图像分析以及YAP、p-YAP和LATS1的蛋白质印迹分析。在CHD中观察到明显异常的结构，表现为肺发育不全和血管重塑。这些异常在CDH+TMP组中得到改善。CHD组和CDH+TMP组在内侧壁厚度百分比、小动脉肌化、肺泡计数、AA%和肺泡间隔厚度方面存在显著差异。与对照组相比，CHD组中YAP表达明显增加，产前给予TMP对此无影响。然而，产前TMP干预显著增加了CDH胎儿中LATS1的表达和YAP的磷酸化。我们的结果表明，产前给予TMP可改善CHD大鼠模型中的血管重塑并促进肺发育，可能是通过增加LATS1的表达和YAP的磷酸化来实现的。
