| Background:Periodontitis is a multifactorial chronic infectious disease leading to a host immune response,and primarily caused by all kinds of inflammatory cytokines,especially IL-1β,which is the main reason for the further development of the disease.IL-1 receptor antagonist(IL-1ra)binds IL-1 receptor,inhibiting IL-1β signaling and reducing the levels of other cytokines closely related to periodontitis,such as IL-6 and TNF-α.Therefore,the use of IL-1ra to inhibit periodontitis development in a system,and the guarantee of its sustained release,might be an effective way to combat this disease.Objective:The study is concerned with the effect of a new type of IL-1ra-loaded sustained-release microspheres on a rat model of ligation-induced periodontitis.IL-1ra sustained release microspheres with effective anti-inflammatory action,through the release of long-term,can effectively inhibit inflammation in the gingival tissue and alveolar bone of rats with experimental periodontitis caused by absorption.The investigation of the role of IL-1ra release microspheres in a rat model of periodontitis provides a theoretical basis for clinical application.Methods:The experiment was divided into 6 groups,namely no ligation group,ligation control group,ligation + Na Cl group,ligation + blank microsphere group,ligation + IL-1ra group,ligation + IL-1ra/PLGA microspheres group.Except for the blank control group,the orthodontic wires were first applied to other five groups to establish experimental periodontitis models of the maxillary first molars,and then the corresponding group of drugs with the same concentration was locally injected into the target teeth(Na Cl,blank microspheres,IL-1ra and IL-1ra/PLGA microspheres).During the experiment,the rats in each group were weighed and recorded at the same time every day.Two weeks later,the periodontal clinical indicators of the rats(DIS,SBI and TM)were observed and measured.Micro-CT observed the establishment of experimental periodontitis model and the rat’s target alveolar bone resorption.The expression of inflammation-related factors(IL-1β,IL-6,TNF-α)was detected by q RT-PCR,as well as the distance between the target ECJ and ABC and the distance from the cementum of the root furcation to the alveolar bone.Finally,statistical analysis of the differences was conducted between the groups.Results:The IL-1ra sustained-release microsphere group shows the same body weight change curve as the other drug injection groups.It is found from the observation of clinical indicators and Micro-CT that the experimental rat periodontitis model is successfully established.Compared with the blank control group,the ligation group shows obvious gingival bleeding,tooth looseness and alveolar bone resorption.In the ligation group,the IL-1ra sustained-release microspheres group shows better gingival bleeding and reduces tooth looseness under the same soft scale coverage;the results of q RT-PCR shows that the content of inflammatory factors IL-1β and IL-in the ligation group is lower than that of the control group.The expression of TNF-α m RNA is respectively16.30,129.19 and 41.26 times higher than that of the blank control group(P<0.05).The expression of inflammatory factors in the IL-1ra sustained-release microsphere group is significantly lower than that of the ligation + saline group,ligation + blank microsphere group,and ligation + IL-1ra group;HE tissue sections shows that the absorption of the IL-1ra sustained-release microsphere group alveolar bone is closest to the normal group.In conclusion,IL-1ra sustained-release microspheres may be a useful tool to combat periodontal diseases.Conclusion:In the body the rat model of periodontitis,IL-1ra-loaded dextran/PLGA microspheres achieve long-term stable drug release,which inhibit experimental gum inflammation and the loss of alveolar bone,and have potential inhibitory and therapeutic effects on the development or cure of periodontal diseases.IL-1ra-loaded dextran/PLGA microspheres may be a useful tool to combat periodontal diseases. |
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