Neointimal hyperplasia in the inferior vena cava of adenine-induced chronic kidney disease rats with aortocaval fistulas
Neointimal hyperplasia in the inferior vena cava of adenine-induced chronic kidney disease rats with aortocaval fistulas
复制标题
DOI：
10.1007/s10157-020-01927-3
复制
发表时间：
2020-07-14
影响因子：
2.3
通讯作者：
Xu, Dongmei
中科院分区：
文献类型：
--
作者：
Du, Jing;Liang, Liming;Xu, Dongmei
背景自体动静脉瘘（AVF）的失败主要是由于吻合口狭窄，这主要与新生内膜增生（NIH）的发展有关。因此，我们进行了一项研究，以建立一种新的方法来建立腺嘌呤诱导的慢性肾病（CKD）大鼠下腔静脉瘘（ACF），以研究NIH在下腔静脉。方法10只成年雌性大鼠给予含0.75%腺嘌呤的饲料喂养4周，诱导慢性肾脏病（CKD）模型，并进行ACF手术。10只健康大鼠作为对照。在形成瘘时，手术切除紧邻用于形成瘘的静脉部分的5-10 mm静脉段，并将来自同一患者的失败瘘重建作为对照。ACF评估使用双重扫描和组织病理学分析。结果实验结束时，AD大鼠的血清肌酐和尿素氮均高于溶剂组。肾脏组织的显著组织学变化证明了成功的CKD模型。AD大鼠的ACF切片和患者失败瘘重建时取出的静脉表明，偏心性新生内膜形成不规则增厚，新生内膜的细胞较多区域内有几条小血管。免疫组织化学显示新生内膜内存在肌成纤维细胞、收缩性平滑肌细胞和巨噬细胞。结论大鼠ACFs模型具有典型的NIH内瘘狭窄形成特征，与尿毒症患者的临床表现相似。
Background The failure of autologous arteriovenous fistulas (AVFs) occurs primarily due to stenosis in the anastomotic site, which is mainly related to the development of neointimal hyperplasia (NIH). Therefore, we conducted a study to establish a novel approach to create aortocaval fistulas (ACFs) in adenine-induced (AD) chronic kidney disease (CKD) rats to study the NIH in the inferior vena cava. Methods Ten adult female rats received a 0.75% adenine-rich diet for 4 weeks to induce CKD and underwent ACF surgery. Ten healthy rats served as controls. A 5-10-mm segment of a vein immediately adjacent to that the portion of the vein used for creating the fistula was surgically removed at the time of creating the fistula, and reconstruction of the failed fistula from the same patient was used as controls. ACF was assessed using duplex scans and histopathological analyses. Results At the end of the experiment, AD rats showed higher serum creatinine and urea nitrogen than those of vehicle-treated rats. Remarkable histological changes in kidney tissues demonstrated successful CKD models. Sections of the ACF in AD rats and veins removed at the time of the reconstruction of the failed fistula of the patient demonstrated that the eccentric neointima formation is irregularly thickened, with several small vessels within a more cellular region of the neointima. Immunohistochemistry demonstrated the presence of myofibroblasts, contractile smooth muscle cells and macrophages within the neointima. Conclusions Our rat models with ACFs showed typical features of NIH in the formation of fistula stenosis, which can resemble clinical findings in uremic patients.