The Effect Of Periodontitis On Kidney In Obese Mice And Its Possible Mechanism

The association between obesity and chronic kidney disease,and the association between periodontitis and chronic kidney disease have respectively confirmed by many studies.But there is still a lack of direct evidence that in obese body,a state of metabolic abnormalities,will periodontitis impact kidney disease?In this study,periodontitis and obese composite mice model was used to explore in obese body whether periodontitis impact kidney disease and its possible mechanism.This study gave a direct evidence of the periodontitis effect on the development of kidney disease,and provided a basis for multidisciplinary clinical diagnosis,treatment and prevention.The study was divided into three parts described as followings.1.The effect of periodontitis on kidney in obese miceObjective:To establish diet induced obese and experimental periodontitis composite mice model.To study the effect of periodontitis on kidney function and kidney lesions.Method:275 mice was randomly divided into two groups:high fat(HF)or low fat(LF)diet groups.The duration on diet was set into three time points,including 8 weeks,16 weeks and 30 weeks.At the ending of each time point,each diet group was divided into ligation(P,as periodontitis group)or sham-ligation(C,as control)groups.Mice were sacrificed.For 30 weeks mice,the biochemical markers including serum albumin(ALB),total protein(TP),urea(UREA)and creatinine(Cr)were analyzed.And routine HE staining and PAS,MASSON,PASM special staining were administered.Results:The levels of serum TP and ALB decreased significantly in HF groups(HFP and HFC)than in the LF groups(LFP and LFC).However,levels of TP and ALB was not obviously different between HFP and HFC.And there was no significant difference between LFP and LFC.Serum Cr was significantly higher in HFP than in LFP and LFC.But the differences among HFC,LFP and LFC were not significant,so did the difference between HFC and HFP.The levels of serum UREA in HF groups was increased,but there was no significant difference among the four groups.The histological features in LFP were close to LFC showing mainly normal renal histological features.In HFC and HFP groups,there were hyperplasia in glomerular mesangial cells and matrix,and glomerular capillary loop partly disappeared.Also,tubulointerstitial fibroplasia,vacuolar degeneration in cortical tubular epithelial cells and protein cast were observed.The pathologic changes in HFC and HFP were almost similar,but tubulointerstitial fibroplasia was more severe in HFP group.Conclusion:In this study,different degree of diet induced obese and experimental periodontitis.composite mice model was successfully established.The results revealed that periodontitis could not impair kidney in healthy mice,while obese was the main factor of kidney disease.In severe obese mice,like DIO 30 weeks,periodontitis aggravate kidney destruction.2.The effect of different periodontitis induced time and different obese statue on kidneyObjective:To explore the effect of periodontitis on kidney disease by using different induced obese time(DIO 8 weeks,16 weeks,30 weeks)and different periodontitis induced time(5d and 10d).Method:Routine HE staining and PAS,MASSON,PASM special staining were administered for all groups' mice.Result:From DIO 8 weeks to 16 weeks to 30 weeks,hyperplasia in glomerular mesangial cells and matrix was observed in all obese mice.The pathologic changes were almost similar,but there were more hyperplasia in glomerular 30 weeks mice.Also,tubulointerstitial fibroplasia,vacuolar degeneration in cortical tubular epithelial cells was more severe.In DIO 16 weeks obese mice,there were no significant difference between periodontitis 5d and 10d groups.While in DIO 30 weeks mice,tubulointerstitial fibroplasia was more severe in periodontitis 10d mice.Conclusion:The kidney destruction increased with obese statue.And in heavy obese mice(DIO 30 weeks),with the increase of induced periodontitis time,tubulointerstitial fibroplasia was increased.3.The possible mechanism of the effect of periodontitis on kidney diseaseObjective:To study the possible mechanism of the effect of periodontitis on kidney disease in obese mice by detecting the TGF-?1,MMP-2,TIMP-1 protein and mRNA in kidney tissue.Method:Immunohistochemistry was performed to detect TGF-?1,MMP2,TIMP1 protein expression.And expression of TGF-?1,MMP2,TIMP1 mRNA were examined by real-time reverse transcription PCR.Result:The expression of TGF-?1 was different between HFP,HFC,LFP,LFC groups,and there were significantly difference between each two groups.The highest expression of TGF-?1 was observed in HFP.The expression of MMP2 was opposite,the highest expression of MMP2 was observed in LF two groups.The real-time reverse transcription PCR results revealed that the obesity was the main factor,and TGF-?1?MMP2?TIMP1 mRNA were significant difference among HFP,HFC,LFP and LFC four groups.Conclusion:In the presence of obesity,periodontitis not only promoted TGF-?1,TIMP1 expression which was the inhibition of collagen degradation enzymes,but also decreased the MMP2 expression which was the main EDM degradation enzymes.This suggests the possible mechanism of periodontitis effect on kidney disease in obese mice.