Shikonin inhibits inflammation and chondrocyte apoptosis by regulation of the PI3K/Akt signaling pathway in a rat model of osteoarthritis
Shikonin inhibits inflammation and chondrocyte apoptosis by regulation of the PI3K/Akt signaling pathway in a rat model of osteoarthritis
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DOI：
10.3892/etm.2016.3642
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发表时间：
2016-10-01
影响因子：
2.7
通讯作者：
Shi, Guoguang
中科院分区：
文献类型：
--
作者：
Fu, Daijie;Shang, Xifu;Shi, Guoguang
此前已证明紫草素具有抗肿瘤、抗炎、抗病毒等广泛的药理作用。本研究的目的是探讨紫草素的保护作用是否通过抑制炎症和软骨细胞凋亡介导的，并阐明潜在的分子机制在大鼠骨关节炎模型。在健康雄性Sprague-Dawley大鼠中建立骨关节炎模型，腹腔注射紫草素10 mg/kg/d，连续4天。结果发现，紫草素治疗显着抑制炎症反应的大鼠骨关节炎。与假手术组相比，骨关节炎可显著增加白细胞介素（IL）-1、肿瘤坏死因子（TNF）-α和诱导型一氧化氮合酶（iNOS）水平。紫草素治疗可显著抑制骨关节炎大鼠IL-1、TNF-α和iNOS水平的升高。与假手术组相比，骨关节炎大鼠caspase-3活性和环氧合酶（考克斯）-2蛋白表达显著升高，磷酸化Akt蛋白表达显著降低。紫草素可减轻骨关节炎大鼠caspase-3活性、考克斯-2表达和Akt磷酸化的变化。这些结果表明，紫草素抑制炎症和软骨细胞凋亡，通过调节磷酸肌醇3-激酶/Akt信号通路在大鼠骨关节炎模型。
Shikonin has previously been shown to have antitumor, anti-inflammatory, antiviral and extensive pharmacological effects. The aim of the present study was to explore whether the protective effect of shikonin is mediated via the inhibition of inflammation and chondrocyte apoptosis, and to elucidate the potential molecular mechanisms in a rat model of osteoarthritis. A model of osteoarthritis was established in healthy male Sprague-Dawley rats and 10 mg/kg/day shikonin was administered intraperitoneally for 4 days. It was found that shikonin treatment significantly inhibited inflammatory reactions in the rats with osteoarthritis. Osteoarthritis was found to significantly increase interleukin (IL)-1, tumor necrosis factor (TNF)- and inducible nitric oxide synthase (iNOS) levels compared with those in the sham group. However, shikonin treatment significantly inhibited the increases in IL-1, TNF- and iNOS levels in the rats with osteoarthritis. Furthermore, caspase-3 activity and cyclooxygenase (COX)-2 protein expression were significantly increased and phosphorylated Akt protein expression was greatly suppressed in rats with osteoarthritis when compared with the sham group. Shikonin administration attenuated the changes in caspase-3 activity and COX-2 expression and Akt phosphorylation in rats with osteoarthritis. These results indicate that shikonin inhibits inflammation and chondrocyte apoptosis by regulating the phosphoinositide 3-kinase/Akt signaling pathway in a rat model of osteoarthritis.