BioAggregate和MTA对体内破骨细胞分化和功能的影响

目的研究口腔生物陶瓷材料Bio Aggregate及MTA对体内LPS诱导的炎性骨吸收的影响。方法 6周龄C57/BL6雄性小鼠随机分为四组:PBS组、LPS组、Bio Aggregate+LPS组和MTA+LPS组,每组6只。LPS干预小鼠7 d后,取出颅盖骨进行显微-CT扫描、HE染色、酶组织化学染色和组织免疫荧光染色,观察骨破坏面积、破骨细胞的形成以及组织蛋白酶K(cathepsin K)的表达。结果 Bio Aggregate和MTA浸提液明显减少LPS诱导的破骨细胞形成和小鼠颅盖骨炎性骨破坏。与破骨细胞功能密切相关的组织蛋白酶K的表达在Bio Aggregate和MTA浸提液的作用下被显著下调。结论新型口腔生物陶瓷材料Bio Aggregate和传统材料MTA能够抑制体内炎性骨吸收。     

iRoot BP Plus对小鼠炎性骨破坏作用的研究

目的:比较新型口腔生物陶瓷材料iRoot BP Plus和传统材料三氧化矿化聚合物(MTA)对LPS诱导小鼠炎症性骨破坏的影响。方法:24只BABL/C小鼠随机平分为4组,分别注射PBS、LPS(10 mg/kg)、iRoot BP Plus浸提液+LPS和MTA浸提液+LPS,1次/d。7 d后取颅盖骨,通过显微CT扫描、HE染色、酶组织化学和组织免疫荧光染色,观察骨破坏程度、破骨细胞以及组织蛋白酶K的表达。结果:iRoot BP Plus和MTA可有效减轻小鼠颅盖骨炎性骨破坏,抑制破骨细胞的形成和吸收能力,并明显降低与破骨功能相关的组织蛋白酶K的表达。 结论: iRoot BP Plus对小鼠炎性骨破坏有抑制作用。     

主穹隆蛋白通过抑制破骨细胞分化在牙周炎中起骨保护作用

目的:通过建立小鼠实验性牙周炎模型及体外骨髓间充质干细胞(BMMSCs)破骨细胞向诱导,探讨主穹隆蛋白(MVP)在牙周炎骨吸收中的作用。方法:MVP基因敲除(MVP-/-)和野生型(WT)C57BL/6小鼠分别局部注射脂多糖(LPS)以建立实验性牙周炎模型,通过micro CT扫描、耐酒石酸酸性磷酸酶(TRAP)染色等方法检测骨吸收程度。同时,体外分离培养MVP-/-与WT C57BL/6小鼠的BMMSCs,并诱导其向破骨细胞分化,通过TRAP染色、麦胚凝集素(WGA)染色等方法观察MVP对BMMSCs破骨向分化及骨吸收活性的影响。结果:在LPS诱导的小鼠实验性牙周炎中,MVP-/-组小鼠牙周炎骨吸收更为明显,且在注射区域内可见更多破骨细胞;体外实验证明,MVP-/-组小鼠的BMMSCs分化形成更多的破骨细胞,且骨吸收更明显。结论:MVP可以抑制破骨细胞分化,在牙周炎中起骨保护作用。     

辛伐他汀对PTHrP诱导破骨细胞形成及小鼠颅盖骨代谢的影响

目的:探讨辛伐他汀对体外甲状旁腺素相关肽(PTHrP)诱导小鼠的破骨细胞骨吸收功能的作用及其小鼠骨代谢的影响。方法:采用PTHrP诱导小鼠骨髓细胞培养破骨细胞和小鼠颅盖骨培养体系,检测辛伐他汀作用8d后破细胞骨数目和培养上清钙的变化;检测小鼠颅盖骨培养上清碱性磷酸酶和钙含量,组织学观察小鼠颅盖骨形态学变化。结果:辛伐他汀体外可明显抑制PTHrP诱导小鼠的破骨细胞骨吸收陷窝的形成及培养上清钙的释放,辛伐他汀体外可增强小鼠颅盖骨培养上清碱性磷酸酶的活性,组织学观察到辛伐他汀使小鼠颅盖骨矿化增强。结论:辛伐他汀体外不仅可促进小鼠颅盖骨的成骨活性,并且可明显抑制PTHrP诱导小鼠的破骨细胞骨吸收功能,对骨吸收性疾病有着重要的防治作用。     

牙周炎大鼠上颌骨来源的BM-MSCs中破骨细胞相关因子的表达

目的 :研究来源于脂多糖(LPS)诱导的牙周炎大鼠上颌骨的间充质干细胞(MSC)表达破骨细胞因子的变化。方法:注射脂多糖构建牙周炎大鼠模型,6周后,处死大鼠,利用Micro CT观察上颌骨骨吸收情况,HE染色观察牙周组织的变化,抗酒石酸磷酸酶(TRAP)染色观察上颌骨内破骨细胞的数量;体外分离和培养大鼠上颌骨来源的MSCs,荧光定量PCR(q PCR)检测两组间充质干细胞中M-CSF、OPG和RANKL m RNA表达量,并计算OPG与RANKL的比值。结果:Micro CT显示实验组大鼠上颌骨牙槽骨吸收明显;HE染色显示实验组切片中牙龈明显退缩,结合上皮根向增殖,并有炎性细胞浸润;TRAP染色显示实验组上颌骨内破骨细胞数量明显增多;荧光定量PCR显示实验组BMMSCs表达的M-CSF增加,表达的OPG和RANKL减少,但OPG与RANKL的比值减小,差异具有统计学意义。结论:来源于LPS诱导的牙周炎大鼠,其颌骨的间充质干细胞在炎症状态下,表达的与破骨相关因子上调,可能有增强破骨细胞的功能,能加速骨吸收进程。     

牙髓干细胞对牙周炎中破骨细胞的作用

目的研究牙髓干细胞（DPSC）对牙周炎中破骨细胞形成及牙槽骨再生的影响,并初步探索DPSC对小鼠破骨细胞的作用机制。 方法体外诱导小鼠骨髓单核细胞破骨分化,观察破骨细胞组（OC组）及其与DPSC共培养组（OC+DPSC组）的抗酒石酸酸性磷酸酶（TRAP）染色情况,实时荧光定量聚合酶链反应（PCR）检测破骨分化相关基因包括活化T细胞核因子（NFATc1）、基质金属蛋白酶9（MMP-9）及TRAP的表达差异。体内构建小鼠慢性牙周炎模型,通过微计算机体层摄影（micro-CT）扫描后三维重建,比较慢性牙周炎+0.9%氯化钠溶液注射组（NS组）和慢性牙周炎+DPSC注射组（DPSC组）釉牙骨质界至牙槽嵴顶（CEJ-ABC）距离,并对标本进行苏木精-伊红和TRAP染色,观察DPSC对小鼠破骨细胞及牙槽骨再生的影响。采用SPSS 20.0软件进行数据统计分析,采用独立样本t检验及校正t检验分析组间差异。 结果体外TRAP染色发现,与DPSC共培养明显抑制成熟破骨细胞形成,OC+DPSC组成熟破骨细胞均数（4.2 ± 0.2）少于OC组均数（6.8 ± 0.2）,差异有统计学意义（t= 15.922,P<0.001）;破骨细胞表面积均数（0.046 ± 0.007）mm²也明显小于OC组（0.763 ± 0.015）mm²,差异有统计学意义（t = 83.174,P<0.001）。相对OC组,OC+DPSC共培养组的MMP-9、NFATc1及TRAP的mRNA相对表达量明显降低,均值分别为0.38 ± 0.17（t = 6.217,P = 0.003）、0.24 ± 0.12（t = 10.569,P = 0.003）和0.55 ± 0.13（t = 6.077,P = 0.026）。micro-CT扫描结果显示,DPSC注射组CEJ-ABC的平均距离为（0.215 ± 0.017）mm,明显小于0.9%氯化钠溶液组（0.311 ± 0.022）mm,差异有统计学意义（t= 10.921,P<0.001）,组织学观察下DPSC组炎症反应较0.9%氯化钠溶液组轻,且破骨细胞更少。 结论DPSC可通过抑制牙周炎破骨细胞的形成从而促进牙槽骨再生,有望作为一种可局部注射的骨代谢双向调节生物制剂,治疗临床上包括牙周炎等因骨代谢失衡引起的炎症性骨吸收疾病。     

唑来膦酸对小鼠下颌拔牙创早期修复过程的影响

目的: 通过构建小鼠双膦酸盐颌骨坏死（bisphosphonate-related osteonecrosis of the jaw, BRONJ）模型,探讨该类药物对拔牙创早期缺损修复过程的影响。方法: 18只8~9周龄C57BL/6雄性小鼠,随机分为空白对照组及唑来磷酸给药组,通过腹腔注射+左下颌第一磨牙拔除诱导其产生双膦酸盐颌骨坏死样病变。随后选取术后3、5、7天3个时间点,H-E染色观察其大体愈合情况,Trap染色观察破骨细胞分布及数量,免疫组织化学染色观察早期成骨向转录因子及破骨特异性蛋白的表达差异。实验重复3次,采用ImageJ软件对图像进行分析和数据转换,采用SPSS 20.0软件包进行显著性分析。结果: 与对照组相比,唑来膦酸给药组拔牙创早期缺损修复过程延迟。术后3天成骨转录因子RUNX2表达降低,术后7天破骨细胞特异性蛋白CTSK数量减少;术后早期TRAP表达降低,骨改建行为整体受到抑制。结论: 唑来膦酸可在术后3天抑制成纤维细胞长入拔牙窝,并使RUNX2表达含量降低,抑制新骨形成。其还能使拔牙术后3、5、7天破骨细胞表达TRAP含量减少及在术后7天降低CTSK表达量,抑制破骨细胞行使骨吸收功能。     

牙周炎中M1型巨噬细胞与破骨细胞形成相关性研究

目的:探究牙周炎中M1型巨噬细胞与破骨细胞形成的相关性.方法:取2月龄C57BL/6J小鼠,丝线结扎建立右侧上颌牙周炎模型,左侧上颌作为自身对照.术后7 d收样,Micro-CT扫描分析牙槽骨吸收情况,苏木素-伊红(HE)、抗酒石酸酸性磷酸酶(TRAP)、CD80和诱导型一氧化氮合酶(iNOS)免疫荧光染色观察破骨细胞...     

骨细胞与成骨细胞诱导破骨细胞分化的对比研究

目的 比较骨细胞和成骨细胞对破骨细胞分化形成的支持作用,初步探讨骨细胞在骨改建过程中的作用.方法 以小鼠骨髓基质细胞单独培养为空白对照组,以小鼠颅顶骨来源的成骨细胞与小鼠骨髓基质细胞共培养为成骨细胞组,以MLO-Y4骨细胞与小鼠骨髓基质细胞共培养为骨细胞组.使用骨吸收促进因子维生素D3处理3组细胞,抗酒石酸磷酸酶(tartrat resistant acid phosphatase,TRAP)染色后比较维生素D3处理前后3组破骨细胞数量的差异.结果 维生素D3处理前空白对照组破骨细胞计数为(6.0±1.O)个/孔板;成骨细胞组破骨细胞计数为(12.7±5.5)个/孔板,两组差异有统计学意义(P<0.05);骨细胞组破骨细胞计数为(1963.3±93.1)个/孔板,与其他两组间差异均有统计学意义(P<0.001).维生素D3对3组破骨细胞的分化形成均有促进作用.结论 在没有骨吸收促进因子存在的情况下,成骨细胞无法单独诱导破骨细胞分化,而MLO-Y4骨细胞可单独促进破骨细胞分化.骨吸收促进因子维生素D3可加强成骨细胞和骨细胞诱导破骨细胞分化的能力.     

破骨细胞骨吸收上清液对成骨活动影响的实验研究

目的 研究破骨细胞骨吸收活动中的分泌产物对成骨细胞增殖、分化及成骨功能的影响,以了解活化的破骨细胞在体外对成骨细胞的影响.方法 诱导小鼠RAW264.7细胞为破骨细胞,用抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRAP)染色和破骨细胞特异性基因检测鉴定.破骨细胞与牛骨磨片共培养,甲苯胺蓝染色.收集共培养上清液作用于小鼠MC3T3-E1细胞,用甲基噻唑基四唑法(methyl thiazolyl tetrazolium,MTT)法、酶联免疫吸附测定法、茜素红染色及反转录聚合酶链反应检测细胞的增殖、骨钙素水平、矿化及成骨特征基因的表达.结果 TRAP 染色、破骨细胞特异性基因检测及甲苯胺蓝染色表明RAW264.7细胞可分化为具有骨吸收能力的破骨细胞;破骨细胞骨吸收上清液作用后,MC3T3-E1细胞增殖受抑制(A值在0.062±0.004和0.405±0.033之间,P＜0.05);骨钙素水平增高[第10天上清液组的骨钙素质量浓度为(2.965±0.047) μg/L],钙化结节增多,碱性磷酸酶和Runt相关转录因子2的转录增强.结论 RAW264.7破骨细胞骨吸收上清液具有抑制成骨样细胞增殖、促进分化和钙化成骨的作用.     

Effects of CD14 receptors on tissue reactions induced by local injection of two gram-negative bacterial lipopolysaccharides

Lipopolysaccharide (LPS) was recognized by CD14, which may be an important mediator in the deleterious effects of LPS on the periodontal destruction. To investigate the roles of CD14 molecules on LPS-induced soft tissue inflammation and bone destruction, the tissues of CD14-deficient mice were examined histopathologically following a local injection of either Salmonella minnesota or Porphyromonas gingivalis LPS. In the first group, 12 mice received a local injection of 500 microg of purified P. gingivalis LPS and six mice were injected with saline to the calvaria as controls. In the second group 13 mice were injected subcutaneously on the laterally abdominal skin with 50 microg of S. minnesota LPS and three mice were injected with PBS. Mice were sacrificed at day 5. After histological preparation, the tissue sections of calvaria and soft tissue specimen were stained with tartrate-resistant acid phosphatase (TRAP) marker for osteoclast and macrophage. The soft tissue sections were also stained with hematoxylin & eosin (H&E). Resorption surface and osteoclast index were measured to quantify bone resorption. Necrotic area and inflammatory cell numbers were estimated to assess the situation of local inflammation. Our results indicated that LPS-induced bone resorption is inhibited in CD14-deficient mice. An increase in the number of total inflammatory cells was noticed in both CD14-deficient mice and wild-type mice; however, the cell numbers were less in CD14-deficient mice than those in wild-type mice (two- to three-fold decrease). Therefore, we conclude that the LPS-stimulated bone resorption is mainly via CD14 receptor but the LPS-induced soft tissue inflammation appears to be partially dependent on the receptor.     

Lack of Toll-like receptor 4 decreases lipopolysaccharide-induced bone resorption in C3H/HeJ mice in vivo

Introduction:  Few in vivo studies have demonstrated whether Toll-like receptor 4 (TLR4) is indispensable for lipopolysaccharide (LPS)-induced bone resorption and little is known about the receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression induced by LPS under conditions of lack of TLR4.
Methods:  We compared bone resorption histomorphometrically in C3H/HeN and C3H/HeJ mice that were repeatedly injected with Actinobacillus actionmycetemcomitans LPS into their gingiva every 48 h. RANKL-, interleukin-1β- and OPG-positive cells in the connective tissue were also compared immunohistochemically.
Results:  Bone resorption in C3H/HeJ mice in the fourth, seventh, and tenth injection groups was significantly less than that C3H/HeN mice ( P  < 0.05). The number of RANKL-positive cells in C3H/HeJ mice in the 10th injection group was significantly smaller than that in C3H/HeN mice ( P  < 0.05). The numbers of interleukin-1β-positive cells in C3H/HeJ mice in the seventh and tenth injection groups were significantly decreased compared with those in C3H/HeN mice ( P  < 0.05). The numbers of OPG-positive cells in C3H/HeN and C3H/HeJ mice gradually increased, but there was no significant difference between the two strains of mice.
Conclusion:  TLR4 is indispensable for LPS-induced bone resorption in vivo .     

Effect of high-density lipoprotein on lipopolysaccharide-induced alveolar bone resorption in rats

OBJECTIVE: To determine whether treatments with high-density lipoprotein (HDL) may alter the lipopolysaccharide (LPS)-induced alveolar bone resorption in rats. MATERIALS AND METHODS: Rats were injected with 500 microg of LPS from Escherichia coli at the alveolar mucosa of lower right first molar once every 2 days for 8 days. The negative and positive control were injected with phosphate buffered saline (PBS) and LPS alone, respectively. In HDL-treated animals various concentration of HDL were injected immediately before, after the third or the final LPS injection. The bone sections were stained with tartrate-resistant acid phosphatase (TRAP) and the numbers of both osteoclasts and preosteoclasts and the levels of alveolar bone resorption were assessed. RESULTS: The numbers of both osteoclasts and preosteoclasts and the levels of alveolar bone resorption in animals treated with HDL before or during LPS injections were lower than those in the positive control, but higher than those in the negative control, regardless of HDL doses. Similar results were also observed in animals treated with 250 and 500 microg of HDL after the final LPS injection. Only treatments with 1000 microg of HDL after LPS injections completely reduced the number of both osteoclasts and preosteoclasts, but only partially decreased the alveolar bone resorption. CONCLUSION: HDL treatments partially reduced the LPS-induced alveolar bone resorption in vivo in rats, suggesting that HDL may neutralize the ability of LPS to induce alveolar bone resorption.     

雷洛昔芬对牙周炎合并系统性绝经后骨质疏松症小鼠模型局部牙槽骨破坏的影响

目的：探讨雷洛昔芬对牙周炎合并系统性绝经后骨质疏松症（PMO）小鼠模型局部牙槽骨破坏的影响。方法：无特定病原级雌性成熟Wistar小鼠,适应性喂养7 d 后,随机分为空白组（保留两侧卵巢,只切除卵巢组织周围与卵巢重量相当的脂肪组织）、对照组（切除两侧卵巢+口腔正畸结扎丝结扎）、实验组（切除两侧卵巢+口腔正畸结扎丝结扎+雷洛昔芬试剂）,每组各15只。术后4周拍摄CT,检测骨密度和骨吸收情况,体视显微镜观察牙槽骨破坏情况,酶联免疫吸附测定法（ELISA）检测破骨相关因子白细胞介素1(IL-1)、IL-1α、转化生长因子(TGF)、肿瘤坏死因子α(TNF-α)、TNF-β的表达水平。采用SPSS 18.0软件包对数据进行统计学分析。结果：对照组新骨形成少于实验组。亚甲蓝染色结果显示,对照组小鼠骨显著吸收,体视显微镜下可见骨破坏,实验组小鼠骨吸收程度较轻。与空白组相比,对照组、实验组牙槽骨密度降低而牙槽骨丧失、IL-1、IL-1α、TGF、TNF-α、TNF-β显著升高（P<0.05）;对照组牙槽骨密度显著低于实验组（P<0.05）,牙槽骨丧失、IL-1、IL-1α、TGF、TNF-α、TNF-β显著高于实验组（P<0.05）。结论：雷洛昔芬可减少PMO牙周炎症小鼠牙槽骨吸收、破骨细胞因子表达,防止牙槽骨破坏而有效防止牙周炎进展。     

淫羊藿苷口服给药对骨质疏松牙周炎小鼠牙槽骨吸收的影响

目的:研究口服淫羊藿苷（ICA）对骨质疏松小鼠牙周炎引起的牙槽骨吸收的抑制作用。方法:3月龄、雌性、C57BL/6J小鼠随机分为3组,即正常组（SHAM组）、卵巢切除+口腔涂布牙龈卟啉单胞菌（Pg）+淫羊藿苷组（OVX+Pg+ICA）、卵巢切除+Pg口腔涂布组（OVX+Pg）。小鼠适应性喂养1周,第2周进行双侧卵巢切除术,诱导小鼠骨质疏松形成。从第4周开始,对小鼠牙周涂布Pg,1次/d,连续1周。第12周收集左侧下颌骨进行固定切片及染色,分析各组之间牙槽骨吸收高度的差异。收集右侧下颌骨进行亚甲蓝染色,分析各组间牙槽骨吸收面积的差异;收集双侧上颌骨牙周组织蛋白,分析成骨相关蛋白的表达差异。采用SPSS16.0软件包对数据进行统计学分析。结果:小鼠股骨及牙周组织切片染色显示,成功建立了小鼠骨质疏松牙周炎模型。对牙槽骨吸收距离和面积的测量分析显示,相比于OVX+Pg组,口服淫羊藿苷可显著减少釉-牙骨质界-牙槽嵴顶（CEJ-ABC）的距离及颊舌侧牙槽骨吸收面积（P<0.05）;Western免疫印迹显示,相比于OVX+Pg组,OVX+Pg+ICA组中Runx2、OSX、OCN及OPN蛋白表达水平显著升高（P<0.05）。结论:口服淫羊藿苷在预防小鼠骨质疏松发生的同时,可有效减少牙周炎引起的牙槽骨吸收。     

A p38 mitogen-activated protein kinase inhibitor arrests active alveolar bone loss in a rat periodontitis model

BACKGROUND: Gram-negative bacterial species, such as Actinobacillus actinomycetemcomitans, contain lipopolysaccharide (LPS) that initiates the innate immune system, resulting in inflammatory alveolar bone loss. LPS activates Toll-like receptors on membrane surfaces, stimulating many intracellular signaling cascades, including the p38 mitogen-activated protein kinase (MAPK). Activation of p38 signaling mediates inflammatory cytokine expression, contributing toward osteoclastogenesis and bone loss. The aim of this study was to determine whether the novel, orally active p38 MAPK inhibitor SD282 could arrest progression of LPS-induced alveolar bone destruction in rats. METHODS: Three groups of female Sprague-Dawley rats received LPS injections to the palatal molar gingiva three times per week for 4 weeks to establish periodontitis. From weeks 5 through 8, two groups received the drug SD282 (N = 14) or 1% polyethylene glycol drug vehicle (N = 14) via oral gavage in addition to LPS injections. The third group continued to receive only LPS injections (N = 8). Microcomputed tomography was used to measure volumetric alveolar bone loss, expressed as bone volume fraction (BVF). Expression of interleukin (IL)-1 and -6 and tumor necrosis factor-alpha (TNF-alpha) was assessed by immunohistochemistry, and osteoclasts were enumerated by tartrate-resistant acid phosphatase staining. RESULTS: By 4 weeks, severe alveolar bone resorption was seen in LPS-injected animals. Administration of SD282 significantly blocked additional volumetric bone loss in the LPS-only versus LPS + SD282 groups (0.37 +/- 0.01 BVF versus 0.43 +/- 0.01 BVF; P < 0.01). Significant reductions in IL-1beta (P < 0.01 ), TNF-alpha (P < 0.05), and osteoclast formation (P < 0.01) occurred in the presence of SD282. CONCLUSIONS: An orally active p38 MAPK inhibitor reduced LPS-induced inflammatory cytokine expression, osteoclastogenesis, and alveolar bone loss in rats. Within the limits of the current study, SD282 arrested periodontal disease progression, thus highlighting the therapeutic potential of this novel class of inhibitors.     

睾酮水平对牙周炎小鼠模型炎症性骨吸收的影响及机制探讨

目的：探讨睾酮水平对牙周炎小鼠模型炎症性骨吸收的影响及机制。方法：48只SD小鼠随机分为未结扎组、假手术组、去势组、去势+睾酮组4组,每组各12只,分别进行空白处理、去势模型和牙周炎模型构建。于结扎术后6周采集小鼠内眦静脉血,测定血清睾酮水平。处死小鼠后,取左侧上颌骨组织,进行苏木精-伊红染色和亚甲蓝染色,比较各组小鼠牙槽骨丧失量（alveolar bone loss,ABL）和牙槽骨吸收面积。利用实时荧光定量PCR测定牙龈组织中炎性细胞因子mRNA的表达,同时对血清睾酮水平与ABL、牙槽骨吸收面积及细胞因子进行相关性分析。采用SPSS 20.0软件包对数据进行统计学分析。结果：假手术组、去势组和去势+睾酮组小鼠血清睾酮水平显著低于未结扎组（P<0.05）;去势+睾酮组小鼠血清睾酮水平显著高于假手术组和去势组（P<0.05）;去势组小鼠血清睾酮水平显著低于假手术组（P<0.05）;去势+睾酮组小鼠ABL显著大于未结扎组、假手术组和去势组（P<0.05）,去势组小鼠ABL显著小于假手术组（P<0.05）;去势+睾酮组小鼠牙槽骨吸收面积显著大于未结扎组、假手术组和去势组（P<0.05）,去势组小鼠牙槽骨吸收面积显著小于假手术组（P<0.05）;假手术组、去势组和去势+睾酮组小鼠牙龈组织中白介素1β（IL-1β）mRNA、白介素6（IL-6）mRNA及肿瘤坏死因子α（TNF-α）mRNA水平显著高于未结扎组,白介素10（IL-10）mRNA水平显著低于未结扎组（P<0.05）;假手术组和去势组小鼠牙龈组织中IL-1β mRNA水平显著低于去势+睾酮组,去势组显著低于假手术组（P<0.05）;血清睾酮水平与ABL、牙槽骨吸收面积、IL-1β呈正相关（P<0.05）。结论：牙周炎小鼠睾酮水平降低,睾酮长期耗竭状态可减少牙槽骨炎症性骨吸收,可能通过降低IL-1β水平而实现。合理降低睾酮水平,有可能成为减少牙周炎患者牙槽骨吸收的治疗新思路。     

壳寡糖对牙周炎大鼠牙槽骨吸收及Th17/Treg平衡和OPG/RANKL/RANK通路的影响

目的: 探讨壳寡糖对牙周炎大鼠牙槽骨吸收及Th17/Treg平衡和OPG/RANKL/RANK通路的影响。方法: 建立牙周炎大鼠模型,随机分为模型组、壳寡糖低剂量组、壳寡糖中剂量组、壳寡糖高剂量组和甲硝唑组,每组12只,另取12只作为对照组。分组处理后,评估牙龈指数、牙槽骨吸收值;H-E染色观察牙周组织病理形态学变化;流式细胞术检测外周血中Th17/Treg细胞比值;酶联免疫吸附试验（ELISA）检测各组大鼠血清中IL-17、TGF-β、RANKL、OPG水平,实时荧光定量PCR（qRT-PCR）检测各组大鼠牙周组织OPG、RANKL mRNA表达水平。采用SPSS 24.0软件包对数据进行统计学分析。结果: 与对照组相比,模型组大鼠牙周组织呈现牙周膜纤维束断裂、排列紊乱,毛细血管扩张、增生,炎症细胞浸润等病理损伤;牙龈指数、牙槽骨吸收值、Th17/Treg比值、血清RANKL及IL-17水平、牙周组织RANKL mRNA水平显著升高（P<0.05）,血清OPG及TGF-β水平、牙周组织OPG mRNA水平显著降低（P<0.05）。与模型组相比,壳寡糖低、中、高剂量组和甲硝唑组大鼠牙周组织病理损伤减轻;牙龈指数、牙槽骨吸收值、Th17/Treg比值、血清RANKL及IL-17水平、牙周组织RANKL mRNA水平显著降低（P<0.05）,血清OPG及TGF-β水平、牙周组织OPG mRNA水平显著升高（P<0.05）,且壳寡糖各组呈剂量依赖性,壳寡糖高剂量组与甲硝唑组相比,差异无统计学意义（P>0.05）。结论: 壳寡糖可促使Th17/Treg平衡恢复正常,上调OPG表达,下调RANKL表达,抑制牙周炎大鼠牙槽骨吸收,改善其临床症状。