Zhang Yuqing, Zhu Rujian, Liu Dong, Gong Min, Hu Wei, Yi Qingtong, Zhang Jie
Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.
School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Transl Androl Urol. 2019 Dec;8(6):619-630. doi: 10.21037/tau.2019.11.14.
Calcifying nanoparticles (CNPs) has been associated with the occurrence and development of kidney stones, but the exact mechanism is not clear. This study aimed to establish a rat model of CNP-induced renal epithelial injury and assess the efficacy of tetracycline in preventing this injury.
Kidney stones from patients after percutaneous nephrolithotomy (PCNL) were collected to isolate and culture CNPs. Thirty Sprague-Dawley rats were divided into three groups: the sham group (G1), the CNP group (G2), and the CNP + tetracycline group (G3). Rats in G2 and G3 were given an intravenous injection of CNPs via the tail vein, while rats in G1 were given saline. Meanwhile, rats in G3 were given tetracycline by gavage twice a day at a dose of 25 mg/kg. After 8 weeks, the 24-h urine of all rats was collected, and all rats were sacrificed to obtain blood and kidneys.
The results revealed that in G2, activities of antioxidant enzymes such as superoxide dismutase and catalase were significantly lower than those in G1, while malondialdehyde activity in G2 was significantly higher than that in G1 and both of them were inhibited by tetracycline co-treatment in G3. CNPs significantly increased expression of inflammatory cytokines, including monocyte chemotactic protein 1 and interleukin 6, which were largely alleviated in G3. CNPs significantly increased TUNEL-positive cells and the apoptosis activity of Bcl2-associated X protein but decreased B-cell lymphoma-2 level compared with that in G1, and was limited by tetracycline co-treatment in G3. Furthermore, CNPs led to notable renal tubular epithelial cell damage, hyaline cast formation, desquamation, swelling, vacuolization in histology, all of which were alleviated by tetracycline.
Tetracycline can attenuate CNP-induced renal epithelial injury through suppression of inflammation, oxidative stress, and apoptosis.
钙化纳米颗粒（CNPs）与肾结石的发生发展有关，但其确切机制尚不清楚。本研究旨在建立CNP诱导的大鼠肾上皮损伤模型，并评估四环素预防这种损伤的效果。
收集经皮肾镜取石术（PCNL）后患者的肾结石，以分离和培养CNPs。将30只Sprague-Dawley大鼠分为三组：假手术组（G1）、CNP组（G2）和CNP+四环素组（G3）。G2和G3组大鼠通过尾静脉静脉注射CNPs，而G1组大鼠注射生理盐水。同时，G3组大鼠每天经口灌胃给予剂量为25mg/kg的四环素两次。8周后，收集所有大鼠的24小时尿液，并处死所有大鼠以获取血液和肾脏。
结果显示，在G2组中，超氧化物歧化酶和过氧化氢酶等抗氧化酶的活性显著低于G1组，而G2组中的丙二醛活性显著高于G1组，并且两者在G3组中通过四环素联合治疗受到抑制。CNPs显著增加炎症细胞因子的表达，包括单核细胞趋化蛋白1和白细胞介素6，而在G3组中这些炎症细胞因子的表达在很大程度上得到缓解。与G1组相比，CNPs显著增加TUNEL阳性细胞以及Bcl2相关X蛋白的凋亡活性，但降低了B细胞淋巴瘤-2水平，并且在G3组中通过四环素联合治疗受到限制。此外，CNPs导致明显的肾小管上皮细胞损伤、透明管型形成、脱屑、肿胀、空泡化变化，而这些变化均通过四环素得到缓解。
四环素可通过抑制炎症、氧化应激和细胞凋亡来减轻CNP诱导的肾上皮损伤。
