阿仑膦酸钠对内毒素诱导的大鼠模型颅骨缺损修复作用的研究  

Effect of alendronate sodium on lipopolysaccharide-induced repair of skull defects in rats

作　　者：胡椹 王静霞[1] 张晓彬 陈屿恒 倪茂君[1] 田珊珊 彭朝荣 Hu Zhen;Wang Jingxia;Zhang Xiaobin;Chen Yuheng;Ni Maojun;Tian Shanshan;Peng Chaorong(Institute of Radiation Chemistry,Sichuan Institute of Atomic Energy,Chengdu 610101,China;Prehospital Emergency Department,Chongqing Emergency Medical Center&Chongqing University Central Hospital,Chongqing 400014,China;Sichuan Provincial Key Laboratory of Irradiation Preservation,Chengdu 610101,China)

机构地区：[1]四川省原子能研究院辐射化学研究所,成都610101 [2]重庆市急救医疗中心,重庆大学附属中心医院院前急救部,400014 [3]辐照保藏四川省重点实验室,成都610101

出　　处：《神经疾病与精神卫生》2025年第3期161-170,共10页Journal of Neuroscience and Mental Health

基　　金：四川省科技计划省院省校合作项目(2022YFSY0003)。

摘　　要：目的探讨一定剂量内毒素(LPS)对大鼠颅骨缺损修复的影响以及阿仑膦酸钠(ALN)在改善颅骨缺损修复中的作用。方法将20只SD雄性大鼠随机分为空白组、对照组、LPS组与LPS+ALN组,建立LPS诱导及LPS联合ALN给药的颅骨缺损修复动物模型。采用显微CT(Micro-CT)观察大鼠颅骨修复情况,使用酶联免疫吸附法(ELSIA)检测大鼠血液中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)3种炎症因子水平,利用苏木精-伊红(HE)染色法切片染色观察骨组织结构和细胞,采用抗酒石酸酸性磷酸酶(TRAP)切片染色考察颅骨缺损处处破骨细胞的状态,采用免疫组化研究骨生长及骨吸收的影响机制。结果检测因子结果表明,与空白组或对照组比较,LPS引起红细胞、血红蛋白及血小板表达水平变化(P<0.05),而ALN给药治疗后IL-1β(P=0.014)、IL-6(P=0.049)及TNF-α(P=0.006)炎症因子水平变化,差异均有统计学意义。与空白组相比,Micro-CT显示对照组、LPS组及LPS+ALN组均发生明显骨吸收,但LPS组在第2天时发生明显颅骨间吸收,而ALN治疗后吸收被抑制。病理结果显示,LPS导致破骨细胞的增多,引起骨质丢失和骨结构缺损,颅骨发生明显骨吸收现象;而LPS+ALN组发生骨吸收较少,46 d时成骨细胞分化的标志物骨钙素和转化生长因子-β表达最少,修复速度高于其他组。结论LPS浸泡会导致一定的骨吸收,不利于大鼠颅骨细胞增殖分化,ALN治疗可有效加速骨生成并抑制LPS导致的炎症骨吸收,从而改善颅骨的修复效果。Objective To explore the effect of a certain dose of endotoxin,lipopolysaccharide(LPS)on skull repair in rats and the role of alendronate sodium(ALN)in improving skull repair.Methods Twenty SD male rats were randomly divided into blank,control,LPS and LPS+ALN groups to establish an animal model of LPS-induced and LPS-combined ALN for skull defect repair.Microscopic computed tomography(Micro-CT)was used to observe the skull repair in rats,enzyme-linked immunosorbent assay(ELSIA)was used to detect the levels of three inflammatory factors,namely interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),in the blood of rats,and hematoxylin-eosin(HE)staining was utilized to observe the bone structure and cells.The status of osteoclasts at the skull defect was examined using tartrate resistant acid phosphatase(TRAP)staining of sections,and the mechanism of bone growth and bone resorption was investigated using immunohistochemistry.Results The results of the tested factors showed that,compared with blank group or control group,LPS caused abnormal expression of erythrocytes,hemoglobin,and platelets with a statistical difference(P<0.05),and there were statistically significant differences in inflammatory factors such as IL-1β(P=0.014),IL-6(P=0.049),and TNF-α(P=0.006)after ALN administration.Compared with blank group,Micro-CT showed that significant bone resorption occurred in control group,LPS group,and LPS+ALN group,but significant intercranial resorption occurred in LPS group on day 2,while resorption was suppressed after ALN treatment.(3)Analyzing the pathological results,LPS led to an increase in osteoclasts,causing bone loss and bone structure defects,and significant bone resorption occurred in the skull,while less bone resorption occurred in LPS+ALN group,and the markers of osteoclast differentiation,osteocalcin and transforming growth factor-β,were least expressed at 46 days,with a higher rate of repair than in the other groups.Conclusions LPS immersion triggers bone resorption,which is det

关 键 词：颅骨修复 内毒素 阿仑膦酸钠 骨吸收 大鼠 

分 类 号：R73[医药卫生—肿瘤]