Liu Jian-Rong, Mao Hong-Jiao, Guo Gao-Li, Fu Jing-Lei, Tong Xia, Qian Qin-Qing, Luo Hua-Gang, Zhang Yun
Department of Basic Medicine, College of Medicine, Shaoxing University, Shaoxing 312000, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Apr 8;34(4):355-359. doi: 10.12047/j.cjap.5639.2018.081.
To explore the effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism.
Thirty-six male ICR mice were randomly divided into three groups (=12):sham group, TCP wear particles (TCP) group and N-acetyl-L-cysteine (NAC) group. Aperiprosthetic osteolysis model in mouse was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2nd day post-operation, NAC (1.0 mg/kg) was locally injected to the calvarium under the periosteum every other day for 2 weeks. Then, all the mice were sacrificed to obtain blood and the calvaria. Periprosthetic osteolysis in the mouse calvaria was observed by tartrate resistant acid phosphatase (TRAP) staining; serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6); total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) activity were examined by ELISA and chemical colorimetry, respectively; protein levels of glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phospho-PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α) and phospho-eIF2α (p-eIF2α) in periprosthetic bone tissue were detected by Western blot.
Compared with sham group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were increased obviously in TCP group (<0.05), and serum level of T-AOC and SOD activity were decreased significantly in TCP group (<0.05), GRP78 expression, the ratio of p-PERK and PERK, p-eIF2α and eIF2α in the mouse calvaria of TCP group were up-regulated markedly. Compared with TCP group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were decreased markedly in NAC group (<0.05), serum level of T-AOC and SOD activity were increased obviously in NAC group (<0.05), and GRP78 expression, the ratio of p-PERK/PERK and p-eIF2α/eIF2α were obviously down-regulated.
Inhibition of oxidative stress can prevent periprosthetic osteolysis induced by TCP wear particles, which may be mediated by inactivation of PERK/eIF2α signaling pathway.
探讨氧化应激对小鼠颅骨中TCP磨损颗粒诱导的假体周围骨溶解的影响及其机制。
将36只雄性ICR小鼠随机分为三组（每组 = 12只）：假手术组、TCP磨损颗粒（TCP）组和N - 乙酰 - L - 半胱氨酸（NAC）组。去除骨膜后，在双侧顶骨表面植入30 mg TCP磨损颗粒，建立小鼠假体周围骨溶解模型。术后第2天，每隔一天在骨膜下向颅骨局部注射NAC（1.0 mg/kg），共2周。然后，处死所有小鼠，获取血液和颅骨。通过抗酒石酸酸性磷酸酶（TRAP）染色观察小鼠颅骨中的假体周围骨溶解情况；分别采用ELISA和化学比色法检测血清肿瘤坏死因子 - α（TNF - α）、白细胞介素 - 1β（IL - 1β）、白细胞介素 - 6（IL - 6）水平；总抗氧化能力（T - AOC）和超氧化物歧化酶（SOD）活性；通过蛋白质印迹法检测假体周围骨组织中葡萄糖调节蛋白78（GRP78）、蛋白激酶R样内质网激酶（PERK）、磷酸化PERK（p - PERK）、真核起始因子2α（eIF2α）和磷酸化eIF2α（p - eIF2α）的蛋白水平。
与假手术组相比，TCP组血清TNF - α、IL - 1β和IL - 6水平及骨溶解面积明显增加（P < 0.05），TCP组血清T - AOC水平和SOD活性明显降低（P < 0.05），TCP组小鼠颅骨中GRP78表达、p - PERK与PERK的比值、p - eIF2α与eIF2α的比值明显上调。与TCP组相比，NAC组血清TNF - α、IL - 1β和IL - 6水平及骨溶解面积明显降低（P < 0.05），NAC组血清T - AOC水平和SOD活性明显增加（P < 0.05），GRP78表达、p - PERK/PERK和p - eIF2α/eIF2α的比值明显下调。
抑制氧化应激可预防TCP磨损颗粒诱导的假体周围骨溶解，其机制可能是通过PERK/eIF2α信号通路失活介导的。
