Effect Of Porphyromonas Gingivalis On HMGB1/TLR-4/PI3K/AKT Signaling Pathway In Diabetic Rats

Objective:To explore the effect of Porphyromonas gingivalis on diabetic rats via HMGB1/TLR-4/PI3K/AKT signal pathway.Method:20 selected 4-6 weeks old male SD rats were randomly divided into control group(NC group),vein injection of P.g group(NC+Ⅰ.Ⅴ.group),diabetic group(DM group)and Diabetic+vein injection of P.g groups(DM+Ⅰ.Ⅴ.group),with 5 rats in each group.NC group,NC+Ⅰ.Ⅴ.group were feed with conventional diet.For DM group and DM+Ⅰ.Ⅴ.group,after 4 weeks of high-fat feed 4,STZ was used to construct diabete model.From the 6th week,P.g(0.1ml)was injected to the NC+Ⅰ.Ⅴ.and DM+I.V.Group 5 times per week for 6 weeks.The blood sugar and weight of the four groups were recorded once a week.On the 13th week,blood glucose level,hepatic serum biochemical indicators,such as TC,TG,HDL-C,LDL-C and serum liver injury indicator-ALT was detected.HE,Masson staining and Immunohistochemistry staining of the liver samples were observed.Fecal samples were analyzed by High-throughput sequencing to observe the change in gut microbiota.Results:After abdominal injection of STZ,the blood glucose level of DMgroup and DM+Ⅰ.Ⅴ.group was significantly increased(≥13.9mmol/L).ALT level of the DM group was significantly increased,when compared withthe NC group and the NC+Ⅰ.Ⅴ.group(P<0.01).HE staining showed liver damage inDM group and DM+Ⅰ.Ⅴ.group.Masson staining showed that the liver fibrosis extent ofDM+Ⅰ.Ⅴ.group significantly higher than in other three groups(P<0.05).Immunohistochemical results show that theHMGB1 expression level of the DM+Ⅰ.Ⅴ.group was significantly higher than in the NC group and DM group(P<0.05);The TLR-4 expression level of the DM group and the DM+I.V.group were significantly higher than in the NC group(P<0.05);The PI3K and AKT expression level of the NC group was significantly higher than in the other three groups(P<0.01).19 bacteria phylum,269 bacteria genuses were detected by High-throughput sequencing of the fecal samples,and the microbial composition of each group were different.Compared with the NC group,the Firmicutes,Campilobacterota,Verrucomicrobiotainthe DM group were significantly increased.Gemmatimonadota in NC+I.V.group was also significantly increased,too.Compared with the DM+Ⅰ.Ⅴ.group,Actinobacteriota,Gemmatimonadota,Fusobacteriota,Myxococcota,Acidobacteriotain DM group were significantly increased.Conclusion:1.The porphyromonas gingivalis may increase the bloodglucose level of diabetic rats.2.Diabetic rats may have chronic liver injuries,porphyromonas gingivalis may fuether aggravate the inflammation.3.Porphyromonas may induce insulin resistance via HMGB1/TLR-4/PI3K/AKT signal pathway.4.The gut microbial composition is different in NC,NC+Ⅰ.Ⅴ.,DM and DM+Ⅰ.Ⅴ.group.