牙周炎对肥胖小鼠炎症因子、肾纤维化的影响
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常州市卫生和计划生育委员会项目资金资助(WZ201704);常州市卫计委青年人才科技项目(QN201708)


Effects of periodontitis on inflammatory factors and renal fibrosis in obese mice
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    摘要:

    目的:初步探索牙周炎对肥胖小鼠炎症因子、肾损伤的影响。方法:采用高、低脂饲料诱导小鼠肥胖合并牙周炎的模型,分为高脂牙周炎组(High+Pre)、高脂非牙周炎组(High+NCPre)、低脂牙周炎组(Low+Pre)、低脂非牙周炎组(Low+NCPre);观察小鼠血清总蛋白、白蛋白、肌酐含量的变化;采用免疫印迹试验(Western blot)检测TGF-β1/Samd6信号通路相关蛋白、基质金属蛋白酶(matrixmetalloprotease,MMP)-2、MMP-9、金属蛋白酶组织抑制因子(tissue inhibitor of metalloproteinases-1,TIMP-1)的蛋白水平;应用酶联免疫吸附测定法 (ELISA)检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)水平的变化。结果:高脂饲喂小鼠的体重第20周已达显著肥胖;与Low+NCPre组相比,High+NCPre组和High+Pre组小鼠血清中总蛋白、白蛋白显著降低(P < 0.05),肾组织MMP-2、MMP-9蛋白含量显著下调(P < 0.05),血清肌酐、TNF-α、IL-6显著升高(P < 0.05),肾组织中TIMP-1蛋白水平显著增加(P < 0.05),促进肾组织TGF-β1蛋白表达(P < 0.05),抑制肾组织Samd6、E-cadherin蛋白分泌(P < 0.05);与High+NCPre组相比,High+Pre小鼠血清中总蛋白、白蛋白显著降低(P < 0.05),抑制炎症因子TNF-α、IL-6、MMP-2、MMP-9蛋白表达水平(P < 0.05),血清肌酐、肾组织TIMP-1显著增加(P < 0.05),肾组织TGF-β1蛋白显著上调(P < 0.05),肾组织Samd6、E-cadherin蛋白显著下调(P < 0.05)。结论:牙周炎加重肥胖小鼠肾损伤,其可能通过影响TGF-β1/Samd6信号通路促进肾纤维化,抑制细胞外基质降解,促进上皮间质转化。

    Abstract:

    Objective:This study aims to investigate the effect of inflammatory factors on renal injury in periodontitis model of mice. Methods:High or low fat diet-induced periodontitis models of mice were established. Mice were divided into high fat diet without periodontitis group(High+NCPre),high fat diet with periodontitis group(High+Pre),low fat diet with periodontitis group(Low+Pre),low fat diet without periodontitis group(low+NCPre). The changes of serum total protein,albumin and creatinine in mice were observed. The protein levels of TGF-β1/Samd6 signaling pathway related proteins,MMP-2,MMP-9 and TIMP-1 were detected by Western blot. Changes of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels were detected by enzyme linked immunosorbent assay(ELISA). Results:Mice fed with high fat diet were significant obesity at the 20th week. Compared with those in Low+NCPre group,the levels of total protein and albumin in serum were significantly decreased in High+NCPre group and High+Pre group(P < 0.05);MMP-2 and MMP-9 protein expression in kidney were significantly decreased (P < 0.05);serum creatinine,TNF-α and IL-6 were increased (P < 0.05);The TIMP-1 protein expression in kidney was significantly increased in High+NCPre group and High+Pre group(P < 0.05). The expression of TGF-β1 protein(P < 0.05)was increased,levels of Samd6 and E-cadherin protein were inhibited in kidney of High+NCPre group and High+Pre group(P < 0.05). Compared with those in High+NCPre group,total protein and albumin in High+Pre group were significantly decreased(P < 0.05);inflammatory factor levels of TNF-α and IL-6,MMP-2 and MMP-9 protein expression decreased;serum creatinine,TGF-β1 and TIMP-1 proteins in kidney increased(P < 0.05);expression of Samd6 and E-cadherin proteins in kidney decreased(P < 0.05). Conclusion:Periodontitis aggravates the renal injury of obese mice,which may promote renal fibrosis,inhibit the degradation of extracellular matrix,and promote the process of epithelial-mesenchymal transition by regulating TGF-β1/Samd6 signaling pathway .

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赵 璐,张 彦,顾 敏.牙周炎对肥胖小鼠炎症因子、肾纤维化的影响[J].南京医科大学学报(自然科学版),2019,(9):1383-1388

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  • 收稿日期:2019-01-29
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  • 在线发布日期: 2019-09-29
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