Exploratory Study Of Linagliptin For Pulp Revascularization

Objectives:To investigate the effects of DPP-4 inhibitor,linagliptin on the blood glucose level and body weight.To evaluate the expression of SDF-1 in serum and root canals by pulp revascularization of mandibular molars in rats and systemic application of linagliptin.Exploring the feasibility and effectiveness of DPP-4 inhibitor in the application of pulp revascularization.Methods:SPF female Sprague-Dawley rats were randomly divided into three groups:?1?experimental group:mandibular first molars with pulp revascularization and oral gavage linagliptin;?2?control group:mandibular first molars with pulp revascularization and oral gavage sodium carboxymethyl cellulose;?3?blank group:normal molars and oral gavage sodium carboxymethyl cellulose.The rats'fasting blood glucose and body weight were detected before experiment and 7 days,14 days,21 days and 28 days after oral gavage.The animals were sacrificed on the 24^th-hour,4th day,7th day,14th day,21st day after pulp revascularization and detected the activity of DPP-4 and the content of SDF-1 in the peripheral blood.The regeneration tissues in root canals was observed by HE staining and evaluated the expression of SDF-1 in root canals by immunohistochemical staining.Results:1.There was no statistical difference in fasting blood glucose or body weight among the three groups at each time point?P>0.05?.2.The serum DPP-4 activity of the experimental group was significantly lower than that of the control group and blank group at each time point?P<0.05?,while the serum SDF-1 content was higher than the other two groups only on the24^th-hour,the 4th day and the 7th day?P<0.05?,and there was no statistical difference between the 14th day and 21st day?P>0.05?.3.The results of HE staining showed that there were a large number of inflammatory cells and red matrix-like structure tissues in the periapical areas and root canals on 24^th-hour and the 4th day after pulp revascularization of the experimental group and the control group.On the 7th day,there were still a lot of inflammatory cells and matrix-like structure tissues that could be observed and extended into the root canals.while on the 14th day and the 21st day after injury,there were less inflammatory cells,and the red matrix-like tissues stained lighter and connected into a vacuole or reticular structure,no cell structure was observed.In the blank group,we could observe that the apical foramen was closed,and there was little inflammatory cells in the periapical areas or root canals.The odontoblasts were arranged in a fence along the root canal walls.Fibroblasts and blood vessels were observed in the center of the pulp,and there was no significant difference in tissue structure at each time point.4.The results of Immunohistochemical staining showed that SDF-1 was highly expressed in inflammatory cells and platelets or erythrocytes in the root canals of the experimental group and the control group at the early stage of periapical injury.With the decreasing of inflammatory cells,red blood cells and platelets,the expression of SDF-1 decreased.In the blank group,SDF-1 was highly expressed in odontoblasts and Fibroblasts,and there was no significant difference in the expression of SDF-1 at each time point.The statistical analysis of Immunohistochemical results showed that the expression level of SDF-1 in the root canals of the experimental group was no statistically different from the two other groups on the 24^th-hour and the 4th day?P>0.05?.However,on the 7th,the14th and the 21st day,there was still no statistical difference between the experimental group and the control group but they were all lower than the blank group?P<0.05?.Conclusions:1.In the time frame of this study,3mg/Kg DPP-4 inhibitor linagliptin has no significant effect on the blood glucose or body weight of normal animals.2.The use of DPP-4 inhibitor linagliptin can increase the content of SDF-1in peripheral blood within 7 days after pulp revascularization.However,the effect of it on the expression of SDF-1 in root canals is not obvious.3.There is no significant cells in the regenerated tissue of the root canals after the pulp revascularization compared with that of pulp-like tissues.4.The concentration gradient of SDF-1 is an important factor in the homing of stem cells into the root canals to participate in pulp regeneration.The results of this study show that linagliptin can increase the concentration of SDF-1 in peripheral blood indirectly.The results of this study showed that linagliptin can increase the concentration of SDF-1 in peripheral blood indirectly.Whether the increase of this concentration affects the concentration gradient of SDF-1,which is the highest in the lesion site and gradually decreased with outward extension,is still unknown and need further study.