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叶黄素通过激活Nrf2信号传导通路抑制糖尿病性骨质疏松模型大鼠氧化应激及炎性反应的机制研究 被引量:12

Mechanism of Lutein Inhibiting Oxidative Stress and Inflammatory Response in Model Rats with Diabetic Osteoporosis by Activating Nrf2 Signal Transduction Pathway
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摘要 目的研究叶黄素缓解糖尿病性骨质疏松(diabetic osteoporosis, DOP)模型大鼠氧化应激及炎性反应的可能机制。方法选取30只健康雌性SD大鼠,随机分为假手术组、模型组、干预组各10只,模型组和干预组大鼠均通过链脲佐菌素诱导糖尿病模型后切除双侧卵巢,假手术组不行糖尿病造模仅分离卵巢但不切除,术后1周干预组大鼠给予200 mg/kg叶黄素灌胃,假手术组及模型组仅予等量0.9%氯化钠注射液灌胃,药物干预8周。末次给药后,对各组大鼠进行骨组织形态学观察及骨密度、血清钙检测,并检测股骨组织超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)及血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平,Western blot法检测各组大鼠股骨组织核因子E2相关因子(Nrf2)、血红素氧合酶-1(HO-1)、醌氧化还原酶1(NQO1)表达水平。结果与假手术组相比,模型组骨密度、血清钙、成骨细胞数降低,破骨细胞数升高,差异有统计学意义(P<0.05);干预组与假手术组相比,骨密度、血清钙降低,破骨细胞数升高,差异有统计学意义(P<0.05);与模型组相比,干预组骨密度、血清钙、成骨细胞数升高,破骨细胞数降低,差异均有统计学意义(P<0.05)。与假手术组相比,模型组和干预组股骨组织MDA含量及ROS荧光强度升高,SOD活性降低,差异有统计学意义(P<0.05);与模型组相比,干预组股骨组织中MDA含量及ROS荧光强度降低,SOD活性升高,差异有统计学意义(P<0.05)。与假手术组相比,模型组和干预组血清TNF-α、IL-1β、IL-6水平均升高(P<0.05);与模型组相比,干预组血清TNF-α、IL-1β、IL-6水平降低(P<0.05)。与假手术组相比,模型组和干预组股骨组织中Nrf2、HO-1、NQO1表达水平降低(P<0.05);与模型组相比,干预组股骨组织中Nrf2、HO-1、NQO1表达水平升高(P<0.05)。结论叶黄素可能通过上调Nrf2信号传导通路,增强抗氧化酶活性,� Objective To study the potential mechanism of lutein relieving oxidative stress and inflammatory response in model rats with diabetic osteoporosis(DOP). Methods Thirty healthy female SD rats were randomly divided into sham operation group, model group and intervention group(n=10 in each group). In model group and intervention group, streptozotocin was applied to induce diabetes model, and then bilateral ovaries were excised. In sham operation group, no diabetic model was established, and ovaries were separated but not excised. At 7 d after modeling, intervention group was given 200 mg/kg lutein by gastric gavage. The sham operation group and the model group were given the same amount of 0.9% sodium chloride lasting for 8 weeks. After the last administration, bone histomorphology observation as well as bone density and serum calcium test was conducted in each group. The levels of superoxide dismutase(SOD), malondialdehyde(MDA), reactive oxygen species(ROS) and tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in femoral tissue were detected by enzyme-linked immunosorbent assay(ELISA). The expression levels of nuclear factor erythroid 2-related factor(Nrf2), heme oxygenase-1(HO-1) and quinone oxidoreductase 1(NQO1) in femoral tissues in each group were detected by Western blot. Results Compared with sham operation group, bone mineral density(BMD), level of serum calcium and the number of osteoblasts were decreased, while the number of osteoclasts was increased in model group(P<0.05). Compared with sham operation group, BMD and level of serum calcium were decreased, while the number of osteoclasts was increased in intervention group(P<0.05). Compared with model group, BMD, level of serum calcium and the number of osteoblasts were increased, while the number of osteoclasts was decreased in intervention group(P<0.05). Compared with sham operation group, MDA content and ROS fluorescence intensity in femoral tissues were increased, while SOD activity was decreased in model group and interven
作者 张卫华 陈东 ZHANG Wei-hua;CHEN Dong(The First Department of Orthopedics,Wuhan Hanyang Hospital,Wuhan 430050,China)
出处 《临床误诊误治》 2020年第7期99-103,共5页 Clinical Misdiagnosis & Mistherapy
基金 湖北省卫生健康委员会2019~2020年度面上项目和血防专项(WJ2019M038)。
关键词 糖尿病并发症 骨质疏松 叶黄素 核因子E2相关因子 Diabetes complication Osteoporosis Lutein Nuclear factor erythroid 2-related factor
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