| Background:Periodontitis is a chronic inflammatory disease,which is characterized by progressive destruction of periodontal support tissue caused by bacterial infection and eventually could lead to tooth loss.It is also a risk factor for many systemic diseases,extremely affecting health of life.The liver is the principal organ of lipid metabolism in the body,while nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide.Studies have confirmed that periodontitis is closely related to NAFLD,and oxidative stress factors may participate in the pathological mechanism of periodontitis-related liver injury,but the specific mechanism is not clear.Oxidative stress is a kind of stress state,which is characterized by overproduction of intracellular reactive oxygen species(ROS)and the imbalance of oxidation and antioxidant systems in vivo under the stimulation of harmful factors,leading to the damage of cell structure and function.Secondly,the triggering of oxidative stress could further cause mitochondrial structural damage and dysfunction,and lead to damage of tissues and cells.Mitochondria are the intracellular main place of energy supply and ROS production.And excessive accumulation of ROS could directly cause mitochondrial structural damage and dysfunction,leading to tissue and cell damage.Peroxisome proliferator activated receptor γ coactivator-1α(PGC-1α),a key transcription regulator of mitochondrial biogenesis,is widely distributed in tissues and organs with high energy demand,such as liver,heart and kidney,etc.In addition,PGC-1α along with its downstream target proteins nuclear respiratory factor1(NRF1),nuclear factor erythroid 2-related factor 2(NRF2)and mitochondrial transcription factor(TFAM),could maintain the balance of oxidation-antioxidant system in vivo by regulating the level of intracellular ROS.In recent years,the relationship between periodontitis and NAFLD has been widely concerned,and oxidative stress may be an important pathogenic factor of periodontitis-related liver injury,however the specific mechanism is uncertain.Therefore,it is very important to explore the pathogenesis of oxidative stress in periodontitis-related liver injury and to find a kind of antioxidant drug with high and remarkable effect.Curcumin is the main active component of Curcuma longa,which has high biosafety and excellent antioxidant activity,furthermore it could significantly alleviate the abnormal expression of oxidative stress in livers of NAFLD rats.Thus,this study aims to explore the mechanism of oxidative stress in the periodontitis-related liver injury by establishing the periodontitis rat model and orally administrating of curcumin as an antioxidant drug,and detecting the related indexes of oxidative stress,and so on,so as to provide a new theoretical basis for the correlation between periodontitis and liver injury.Methods:1.18 Wistar male rats(8 weeks old,weight 210±10 g)were randomly divided into three groups: control group,periodontitis group and curcumin group,with 6 rats in each group.The periodontitis models of rats were constructed by wire ligation combined with Porphyromonas gingivalis(P.gingivalis)vaccination into gingival sulcus for periodontitis group,100 mg/kg curcumin and CMC-Na suspension were given orally the day after ligation and P.gingivalis vaccination in curcumin group,and the same dosage was given for control group.After 6 weeks of modeling,the rats were sacrificed and the samples were taken for subsequent detection.The text indexes were as follows.2.Clinical examination of periodontal tissues: oral photos of periodontal tissues and Micro-CT was used to detect the alveolar bone resorption.3.Pathological observation of liver tissues1)The pathological changes of liver tissues were observed by HE staining;2)The numbers and distribution of lipid droplets in liver tissues were detected by Oil red O staining.4.Related indexes of liver function and oxidative stress: ALT,AST,GSH,MDA and CAT.5.Related indexes of mitochondrial morphology and function: TEM,Mito-ROS,MMP and ATP.6.The expression levels of PGC-1α,NRF1,NRF2 and TFAM in livers of rats were tested respectively by qRT-PCR and immunohistochemistry methods.Results:1.Compared with the control group,the levels of gingival swelling and alveolar bone resorption in periodontitis group were significantly increased,while curcumin could alleviate the above damage(P<0.05);2.The results of liver histopathology showed that compared with the control group,inflammatory cells such as neutrophils appeared in the liver tissues,accompanied by enhanced lipid droplets and vacuolation in the hepatic cells of rats in periodontitis group,while curcumin could reduce the neutrophil infiltration and the formation of intracellular lipid droplets and vacuolation;3.The results of related liver function and oxidative stress indicators showed compared with the control group,the expression levels of ALT and AST in periodontitis group were significantly increased,along with increased levels of oxidative stress related oxidants MDA,decreased levels of antioxidants GSH and CAT in liver tissues.While curcumin could reverse these changes(P<0.05);4.The results of related mitochondrial morphology and function indicators showed compared with the control group,the mitochondria were swollen and deformed in livers of periodontitis group,accompanied by the increase of Mito-ROS level,and the levels of MMP and ATP related to mitochondrial function were decreased,while curcumin could significantly alleviate the above mitochondrial damage(P<0.05);5.qRT-PCR and immunohistochemistry results showed that compared with the control group,the expression levels of PGC-1α,Nrf1,Nrf2 and TFAM in the liver tissues of periodontitis group were significantly decreased,while curcumin significantly increased the expression levels of these antioxidant factors(P<0.05).Conclusions:1.Oxidative stress and mitochondrial dysfunction are important pathological mechanisms of periodontitis-induced liver injury in rats.2.PGC-1α and other related factors may be involved in the process of liver injury induced by periodontitis in rats.3.Curcumin could ameliorate the periodontitis-induced liver injury in rats. |
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