Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Medical Scientist Training Program, University of Pittsburgh, Pittsburgh, PA, USA.
Toxicology. 2022 Jan 15;465:153045. doi: 10.1016/j.tox.2021.153045. Epub 2021 Nov 18.
Exposure to tobacco smoke (TS) has been considered a risk factor for osteonecrosis of the femoral head (ONFH). Soluble epoxide hydrolase inhibitors (sEHIs) have been found to reduce inflammation and oxidative stress in a variety of pathologies. This study was designed to assess the effect of sEHI on the development of ONFH phenotypes induced by TS exposure in spontaneously hypertensive (SH) rats. SH and normotensive Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or TS (80 mg/m3 particulate concentration) 6 h/day, 3 days/week for 8 weeks. During this period, sEHI was delivered through drinking water at a concentration of 6 mg/L. Histology, immunohistochemistry, and micro-CT morphometry were performed for phenotypic evaluation. As results, TS exposure induced significant increases in adipocyte area, bone specific surface (BS/BV), and trabecular separation (Tb.SP), as well as significant decreases in bone mineral density (BMD), percent trabecular area (Tb.Ar), HIF-1a expression, bone volume fraction (BV/TV), trabecular numbers (Tb.N), and trabecular thickness (Tb.Th) in both SH and WKY rats. However, the protective effects of sEHI were mainly observed in TS-exposed SH rats, specifically in the density of osteocytes, BMD, Tb.Ar, HIF-1a expression, BV/TV, BS/BV, Tb.N, and Tb.SP. Our study confirms that TS exposure can induce ONFH especially in SH rats, and suggests that sEHI therapy may protect against TS exposure-induced osteonecrotic changes in the femoral head.
暴露于烟草烟雾（TS）已被认为是股骨头坏死（ONFH）的一个风险因素。已经发现可溶性环氧化物水解酶抑制剂（sEHIs）可减少多种病理中的炎症和氧化应激。本研究旨在评估 sEHIs 对 TS 暴露诱导的自发性高血压（SH）大鼠 ONFH 表型的发展的影响。SH 和正常血压的 Wistar 京都（WKY）大鼠每天暴露于过滤空气（FA）或 TS（80mg/m3 颗粒浓度）6 小时，每周 3 天，持续 8 周。在此期间，sEHIs 通过饮用水以 6mg/L 的浓度给予。进行组织学、免疫组织化学和微 CT 形态计量学以进行表型评估。结果表明，TS 暴露导致 SH 和 WKY 大鼠的脂肪细胞面积、骨特异性表面（BS/BV）和小梁分离（Tb.SP）显著增加，骨密度（BMD）、骨小梁面积百分比（Tb.Ar）、HIF-1a 表达、骨体积分数（BV/TV）、骨小梁数量（Tb.N）和骨小梁厚度（Tb.Th）显著降低。然而，sEHI 的保护作用主要在 TS 暴露的 SH 大鼠中观察到，特别是在成骨细胞密度、BMD、Tb.Ar、HIF-1a 表达、BV/TV、BS/BV、Tb.N 和 Tb.SP 方面。我们的研究证实，TS 暴露可导致 ONFH，特别是在 SH 大鼠中，并且表明 sEHI 治疗可能预防 TS 暴露诱导的股骨头坏死性变化。
