甘草甜素通过核因子-κB/核苷酸结合寡聚结构域样受体蛋白3/白细胞介素-1β信号通路对慢性牙周炎大鼠牙周组织损伤的影响Effects of glycyrrhizin on periodontal tissue damage in rats with chronic periodontitis via the nuclear factor-κB/nucleotide-binding oligomerization domain-like receptor protein 3/interleukin-1β pathway
潘伟伟,李甜女,冯靖
摘要(Abstract):
目的 探究甘草甜素(glycyrrhizin,GL)通过调节核因子-κB(nuclear factor-κB, NF-κB)/核苷酸结合寡聚结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3, NLRP3)/白细胞介素(interleukin, IL)-1β信号通路对慢性牙周炎(chronic periodontitis, CP)大鼠牙周组织损伤的影响。方法 取部分大鼠经牙龈卟啉单胞菌感染建立模型,将建模成功的60只大鼠随机分为模型组、低剂量GL(low-dose GL, L-GL)组、中剂量GL(medium-dose GL, M-GL)组、高剂量GL(highdose GL, H-GL)组(低、中、高剂量组分别静脉注射2、4、10 mg·kg~(-1) GL)、通路激活剂组(静脉注射0.5 mg·kg~(-1) NF-κB/NLRP3/IL-1β通路激活剂CHPG),每组12只;另随机选取12只大鼠作为对照组;其中对照组和模型组静脉注射等量生理盐水,每日1次,持续20 d。采用探针测定牙周探诊深度(probing depth, PD);观察牙齿活动度(tooth mobility, TM);评估出血指数(bleeding index, BI);通过碱性品红染色法测定菌斑指数(plaque index, PLI);通过酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测血清中IL-1β、IL-6、干扰素-γ(interferon-γ, IFN-γ)水平;显微计算机断层扫描(micro computed tomography, Micro-CT)分析牙槽骨吸收情况;采用苏木精-伊红(hematoxylin-eosin, HE)染色和抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase, TRAP)染色观察牙周组织的病理学变化及破骨细胞数量;采用免疫组织化学技术(immunohistochemistry, IHC)和蛋白印迹法(Western blotting)检测牙周组织中NF-κB、NLRP3、IL-1β蛋白的阳性率及表达水平。结果 模型组大鼠出现上皮破裂及大量炎症细胞浸润,提示建模成功;与对照组比较,模型组的IL-1β、IFN-γ、IL-6、PD、TM、BI、PLI、牙骨质-釉质交界(cemento-enamel junction, CEJ)、CEJ到牙槽骨顶(alveolar ridge, ABC)的距离(CEJ-ABC)值、破骨细胞数量,以及NF-κB、NLRP3、IL-1β蛋白的阳性率和表达水平均显著升高(P<0.05);与模型组比较,L-GL组、M-GL组、HGL组的牙周组织损伤得到改善,上述指标均显著降低(P<0.05);通路激活剂则可逆转GL的处理效果。结论 GL可能通过抑制NF-κB/NLRP3/IL-1β通路改善CP大鼠的牙周组织损伤,且该作用呈浓度依赖性。
关键词(KeyWords): 甘草甜素;慢性牙周炎;核因子-κB/核苷酸结合寡聚结构域样受体蛋白3/白细胞介素-1β信号通路;牙周组织损伤;炎症
基金项目(Foundation):
作者(Author): 潘伟伟,李甜女,冯靖
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