艾司氯胺酮对大鼠骨折后骨生长相关因子的影响

Effect of esketamine on bone growth-related factors after fracturing in rats

目的 建立大鼠胫骨骨折模型,观察给予艾司氯胺酮后骨生长相关因子的变化趋势。方法 选取48只雄性SD大鼠建立胫骨骨折模型后,随机均分为2组:实验组(腹腔注射艾司氯胺酮40 mg·kg^(-1)·24 h^(-1),稀释至1 ml),对照组(腹腔注射0.9%氯化钠溶液1 ml),分别于骨折模型建立后第1周、2周、4周取血清并保留大鼠右侧胫骨行脱钙处理,酶联免疫吸附法(ELISA)测血清中降钙素相关基因肽(calcitonin gene-related peptide,CGRP)、胰岛素生长因子1(insulin-like growth factor-1,IGF-1)、神经生长因子(nerve growth factor,NGF)浓度,观察三种因子在骨折愈合中的变化趋势,HE染色观察骨痂部位骨组织的形态学和细胞学。结果 实验组的骨痂体积、新生骨细胞、新生毛细血管均多于对照组(P<0.05),实验组CGRP、IGF-1在各时间点均高于对照组(P<0.05),且CGRP及CGF-1在血清中随时间变化逐渐呈升高趋势,NGF在1周时明显升高,但在2周和4周时较对照组明显降低(P<0.05)。结论 艾司氯胺酮促进骨折愈合过程中,CGRP、IGF-1及NGF可能是促进骨折愈合的相关因素。

Objective To establish a rat tibial fracture model and to observe the changing trend of bone growth-related factors after administration of esketamine.Methods Forty-eight male Sprague-Dawley(SD)rats were subjected to the modeling of tibial fracture,and then randomly divided into the experimental group(intraperitoneal administration of 1 ml of esketamine 40mg/kg/24h)and control group(intraperitoneal administration of the isodose saline solution 0.9%).Serum samples were taken at the first,second and fourth weeks after the establishment of the fracture model,and the right tibia of the rats was collected for decalcification.Serum levels of calcitonin gene-related peptide(CGRP),insulin-like growth factor-1(IGF-1),and nerve growth factor(NGF)were measured by Enzyme-linked immunosorbent assay(ELISA).The morphology and cytology of bone tissues at the osteotylus end were observed by hematoxylin and eosin(H&E)staining.Results The volume of the osteotylus,and the number of newly formed bone cells and capillaries were significantly larger in the experimental group than those in the control group(P<0.05).Expression levels of CGRP and IGF-1 at all time points were significantly higher in the experimental group than those in the control group(P<0.05),and their serum levels gradually increased over time.Serum level of NGF significantly increased at 1 week,which was significantly lower in the experimental group at 2 and 4 weeks than in the control group(P<0.05).Conclusion CGRP,IGF-1 and NGF may be relevant factors for promoting fracture healing by esketamine.