山东大学学报 (医学版) ›› 2024, Vol. 62 ›› Issue (5): 64-71.doi: 10.6040/j.issn.1671-7554.0.2023.0950
• 基础医学 • 上一篇
王莉莎1,王上增2,史栋梁1,张仲博1,任博文1,王云飞1,郭中华1,周晓宁3
WANG Lisha1, WANG Shangzeng2, SHI Dongliang1, ZHANG Zhongbo1, REN Bowen1, WANG Yunfei1, GUO Zhonghua1, ZHOU Xiaoning3
摘要: 目的 探讨乌头汤基于核因子E2相关因子2(nuclear factor E2 related factor 2, Nrf2)/血红素加氧酶-1(heme oxygenase-1, HO-1)通路对膝骨关节炎(knee osteoarthritis, KOA)大鼠模型的治疗作用。 方法 通过向膝关节腔内注射木瓜蛋白酶溶液建立KOA大鼠模型;将造模后的大鼠随机分为KOA组、乌头汤组(4.2 g/kg乌头汤)、抑制剂组(30 mg/kg ML385)、乌头汤+抑制剂组(4.2 g/kg乌头汤+30 mg/kg ML385),每组10只,另取10只大鼠腔内注射生理盐水作为对照组。采用苏木精-伊红染色法观察软骨组织病理学变化并进行损伤评分;采用ELISA法检测血清中炎症因子[肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)/白细胞介素-1β(interleukin-1β,IL-1β)]及氧化应激[丙二醛(malondialdehyde, MDA)、超氧化物歧化酶(superoxide dismutase, SOD)]指标;采用qRT-PCR法及Western blotting法检测Nrf2、HO-1表达。 结果 与对照组相比,KOA组软骨表面粗糙不平,细胞排列紊乱,层状结构消失,IL-1β、TNF-α、MDA含量增加,SOD、Nrf2、HO-1 mRNA及蛋白表达降低,差异有统计学意义(P<0.05);与KOA组相比,乌头汤组病理损伤得到缓解,IL-1β、TNF-α、MDA含量降低,SOD、Nrf2、HO-1 mRNA及蛋白表达增加,差异有统计学意义(P<0.05),但抑制剂组病理损伤进一步加剧,IL-1β、TNF-α、MDA含量增加,SOD、Nrf2、HO-1 mRNA及蛋白表达降低,差异有统计学意义(P<0.05);与乌头汤组相比,乌头汤+抑制剂组病理损伤较为严重,IL-1β、TNF-α、MDA含量增加,SOD、Nrf2、HO-1 mRNA及蛋白表达降低,差异有统计学意义(P<0.05);与抑制剂组相比,乌头汤+抑制剂组病理损伤稍有改善,IL-1β、TNF-α、MDA含量降低,SOD、Nrf2、HO-1 mRNA及蛋白表达增加,差异有统计学意义(P<0.05)。 结论 乌头汤可通过激活Nrf2/HO-1通路对KOA大鼠起治疗作用。
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