Effect Of Esketamine On Bone Growth-related Factors After Fracturing In Rats

Objective:To establish a rat right tibial fracture model and observe the trend of serum calcitonin gene-related peptide,insulin growth factor 1,and nerve growth factor concentrations after intraperitoneal administration of esketamine.Methods:Forty-eight male SD rats were selected to establish a tibial fracture model and randomly divided into two groups: experimental group(esketamine 40 mg/ kg/ 2 4 h)and control group(the same dose of saline was given to the experimental group daily),24 rats in each group,and eight rats were randomly selected from each of the experimental and control groups at the first,second and fourth weeks after the fracture model was established.The concentrations of calcitonin-related gene peptide(CGRP),insulin growth factor 1(IGF-1)and nerve growth factor(NGF)in serum were measured by enzyme-linked immunosorbent assay(Elisa)to observe the changes of the three factors in fracture healing and the morphology and cytology of bone tissue at the site of bone scab were observed by HE staining.Results:At 1,2,and 4 weeks after tibial fracture surgery in rats,the HE staining results showed that the experimental group had more new bone cells,new capillaries,and new bone trabeculae than the control group.At 1,2,and 4 weeks postoperatively,the serum CGRP concentrations of 6.18±0.15pg/ml,6.23±0.10pg/ml,and 6.36±0.09pg/ml in the experimental group were significantly higher than those of 5.88±0.15pg/ml,6.05±0.14pg/ml,and 5.66±0.19pg/ml in the control group,respectively.Increased(P <0.05)and showed an increasing trend with time.At 1,2,and 4 weeks after surgery,the serum IGF-1 concentrations of 3.20±0.11 ng/ml,3.35±0.10 ng/ml,and 3.44±0.08 ng/ml in the experimental group were significantly higher than those of 3.01±0.15 ng/ml,3.21±0.09 ng/ml and 3.16±0.11 ng/ml in the control group,respectively.Significantly increased(P < 0.05)and showed an increasing trend with time.At one week postoperatively,the serum NGF concentration of 61.30±2.77 pg/ml in the experimental group was significantly higher than that of 56.87± 1.82 pg/ml in the control group(P<0.05),and at 2 and 4 weeks postoperatively,the serum NGF concentrations of53.43± 1.83 pg/ml and 55.21± 1.71 pg/ml in the experimental group were significantly higher than those in the control group(P<0.05).The serum NGF concentrations of63.15±2.11 pg/ml and 61.14±3.51 pg/ml in the experimental group were significantly lower than those in the control group at 2 and 4 weeks postoperatively(P<0.05).ConclusionCGRP,IGF-1 and NGF may be relevant factors in the promotion of fracture healing by esketamine.