Effect of Simvastatin Prodrug on Experimental Periodontitis
Effect of Simvastatin Prodrug on Experimental Periodontitis
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DOI：
10.1902/jop.2016.150599
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发表时间：
2016-05-01
影响因子：
4.3
通讯作者：
Reinhardt, Richard A.
中科院分区：
文献类型：
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作者：
Bradley, Aaron D.;Zhang, Yijia;Reinhardt, Richard A.
背景：局部应用他汀类药物在预防和再生实验性牙周炎相关的骨丢失方面显示出潜力。本研究评价了一种新的辛伐他汀（SIM）前体药物（能够向牙周炎炎性病变和细胞递送高剂量）对实验性牙周炎骨丢失和炎症的影响。方法：40只成年雌性Sprague道利大鼠在上颌第一和第二磨牙（M1-M2）之间进行结扎诱导的实验性牙周炎。相等的组用以下的三个每周剂量处理：1）单独的前药载体（mPEG）; 2）在载体中的0.5mg SIM剂量当量（SIM/SIM-mPEG）; 3）1.0mg SIM/SIM-mPEG; 4）1.5mg SIM/SIM-mPEG;或5）单独的结扎。侧磨牙作为未操纵的控制。牙周炎开始后四周，动物被安乐死，M1-M2邻间用显微计算机断层扫描和组织学进行评估，数据用单因素方差分析进行分析。单独结扎导致牙骨质-釉质连接处的平均骨丢失为1.01 +/- 0.06 mm，而所有剂量的SIM/SIM-mPEG均减少骨丢失，尤其是1.5mg SIM/SIM-mPEG（0.68 +/-0.05mm，P < 0.001），其与对侧对照（0.47 +/-0.06mm）没有统计学差异。与单独载体相比，1.5 mg SIM/SIM-mPEG剂量也降低了中性粒细胞的百分比（2.0% +/- 1.0%对5.7% +/- 1.1%; P < 0.05），M1-M2邻间区未发炎结缔组织数量增加（65.2% +/- 3.3%对46.3% +/-3.3%; P < 0.001）。单独的mPEG载体没有骨保护或抗炎property.Conclusion：多个本地1.5毫克剂量的大分子SIM前药减少大鼠实验性牙周炎骨丢失和炎症的量。
Background: Local application of statins has shown potential in preventing and regenerating bone loss associated with experimental periodontitis. This study evaluates the effect of a novel simvastatin (SIM) prodrug (capable of delivering high doses to periodontitis inflammatory lesion and cells) on experimental periodontitis bone loss and inflammation.Methods: Forty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis between maxillary first and second molars (M1-M2). Equal groups were treated with three weekly doses of: 1) prodrug carrier alone (mPEG); 2) 0.5 mg SIM dose equivalent in carrier (SIM/SIM-mPEG); 3) 1.0 mg SIM/SIM-mPEG; 4) 1.5 mg SIM/SIM-mPEG; or 5) ligature alone. Contralateral molars served as unmanipulated controls. Four weeks after initiation of periodontitis, animals were euthanized, the M1-M2 interproximal was evaluated with microcomputed tomography and histology, and data were analyzed with one-way analysis of variance.Results: Ligature alone caused a mean bone loss of 1.01 +/- 0.06 mm from the cemento-enamel junction, whereas all doses of SIM/SIM-mPEG reduced bone loss, especially 1.5 mg SIM/SIM-mPEG (0.68 +/- 0.05 mm, P < 0.001), which was not statistically different from contralateral control (0.47 +/- 0.06 mm). A dose of 1.5 mg SIM/SIM-mPEG also reduced percentage of neutrophils compared with carrier alone (2.0% +/- 1.0% versus 5.7% +/- 1.1%; P < 0.05), and increased amount of uninflamed connective tissue in the M1-M2 interproximal area (65.2% +/- 3.3% versus 46.3% +/- 3.3%; P < 0.001). The mPEG carrier alone did not have bone-sparing or anti-inflammatory properties.Conclusion: Multiple local 1.5-mg doses of a macromolecular SIM prodrug decreases amount of experimental periodontitis bone loss and inflammation in rats.