Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, People's Republic of China.
Int J Nanomedicine. 2020 Dec 3;15:9657-9668. doi: 10.2147/IJN.S275553. eCollection 2020.
To evaluate the effects of ZnO NPs on bone growth in rats and explore the possible mechanisms of action.
Three-week-old male rats received ultrapure water or 68, 203, and 610 mg/kg zinc oxide nanoparticles (ZnO NPs) for 28 days, orally.
The high-dosage groups caused significant differences in weight growth rate, body length, and tibia length (P<0.05), all decreasing with increased ZnO NP dosage. There were no significant differences in body mass index (BMI) (P>0.05). The zinc concentration in liver and bone tissue increased significantly with increased ZnO NP dosage (P<0.05). Clearly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed in the 610 mg/kg ZnO NP group (P>0.05), whereas alkaline phosphatase (ALP) increased in the 610 mg/kg ZnO NP group (P<0.05). Significant differences in insulin-like growth factor type 1 (IGF-1) levels and a decrease in calcium (Ca) levels were observed in 203 and 610 mg/kg ZnO NP groups (P<0.05). Phosphorus (P) levels increased and the Ca/P ratio decreased in the 610 mg/kg ZnO NP group (P<0.05). Micro-computed tomography (micro-CT) of the tibia demonstrated signs of osteoporosis, such as decreased bone density, little trabecular bone structure and reduced cortical bone thickness. Micro-CT data further demonstrated significantly decreased bone mineral density (BMD), trabecular number (Tb.N), and relative bone volume (BV/TV) with increasing dosage of ZnO NPs. Osteoprotegerin (OPG) expression and the ratio of OPG to receptor activator of nuclear factor-κB ligand (RANKL) were statistically lower in the 610 mg/kg ZnO NP group (P<0.05), whereas RANKL expression did not change significantly (P>0.05).
We infer that ZnO NPs affect bone growth in young rats directly or indirectly by altering IGF-1 levels. Overall, the results indicate that ZnO NPs promote osteoclast activity and increase bone loss through the OPG/RANK/RANKL/IGF-1 pathway.
评估氧化锌纳米粒子（ZnO NPs）对大鼠骨生长的影响，并探讨其可能的作用机制。
3 周龄雄性大鼠连续 28 天经口给予超纯水或 68、203、610 mg/kg ZnO NPs。
高剂量组体重增长率、体长和胫骨长度均有显著差异（P<0.05），且随 ZnO NPs 剂量增加而降低。体重指数（BMI）无显著差异（P>0.05）。肝组织和骨组织中的锌浓度随 ZnO NPs 剂量增加而显著升高（P<0.05）。610 mg/kg ZnO NP 组天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平明显升高（P>0.05），碱性磷酸酶（ALP）在 610 mg/kg ZnO NP 组升高（P<0.05）。203 和 610 mg/kg ZnO NP 组胰岛素样生长因子 1（IGF-1）水平有显著差异且钙（Ca）水平降低（P<0.05）。610 mg/kg ZnO NP 组磷（P）水平升高，Ca/P 比值降低（P<0.05）。胫骨 micro-CT 显示骨质疏松的迹象，如骨密度降低、小梁骨结构减少和皮质骨厚度减少。micro-CT 数据进一步表明，随着 ZnO NPs 剂量的增加，骨矿物质密度（BMD）、小梁数（Tb.N）和相对骨体积（BV/TV）显著降低。610 mg/kg ZnO NP 组骨保护素（OPG）表达及其与核因子-κB 受体激活剂配体（RANKL）的比值显著降低（P<0.05），而 RANKL 表达无明显变化（P>0.05）。
我们推断 ZnO NPs 通过改变 IGF-1 水平直接或间接影响幼年大鼠的骨生长。总之，结果表明 ZnO NPs 通过 OPG/RANK/RANKL/IGF-1 途径促进破骨细胞活性并增加骨丢失。
Zotero 插件
