p38MAPK信号通路在慢性牙髓炎疼痛大鼠中的表达及作用机制研究
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摘要
目的:研究p38MAPK信号通路在慢性牙髓炎疼痛大鼠中的表达及作用机制。方法:选取SPF级Wistar雄性大鼠25只,将大鼠分成3组,正常组5只,模型组15只,MAPK抑制剂组5只。MAPK抑制剂组、模型组大鼠制备牙髓炎模型,成功造模后MAPK抑制剂组由颈静脉注入剂量为5 mg/kg的SB203580,连续注射14 d;造模后14 d选取MAPK抑制剂组和正常组大鼠及造模3、7、14 d模型组分别选取5只大鼠处死,观察其牙髓组织病理、血清白细胞介素-6(IL-6)、IL-8含量、牙髓组织内p-p38MAPK、ERK、p-ERK、p38MAPK蛋白表达及p38MAPK、ERK mRNA表达。结果:和正常组相比,造模后3、7、14 d大鼠根尖破损水平长度、根尖周牙周膜宽度及第一磨牙根髓坏死比率显著升高;和造模后3、7、14 d相比,MAPK抑制剂组大鼠根尖破损水平长度、根尖周牙周膜宽度及第一磨牙根髓坏死比率显著降低,差异有统计学意义(P<0.05);和正常组相比,造模后3、7、14 d大鼠血清IL-6、IL-8含量显著升高;和造模后3、7、14 d相比,MAPK抑制剂组大鼠血清IL-6、IL-8含量显著降低,差异有统计学意义(P<0.05);和正常组相比,模型组大鼠牙髓组织内p-p38MAPK、p-ERK蛋白表达升高;和模型组相比,MAPK抑制剂组大鼠牙髓组织内p-p38MAPK、p-ERK蛋白表达降低,差异有统计学意义(P<0.05)。结论:慢性牙髓炎大鼠牙髓组织内p38MAPK信号通路激活增大了炎症反应程度,促进病情进展,抑制p38MAPK信号通路可有效降低炎症因子表达。
AIM: To investigate the expression of p38MAPK signaling pathway in chronic pulpitis pain rats and its mechanism of action. METHODS: Twenty-five Wistar male rats of SPF grade were selected and divided into 3 groups, 5 in normal group, 15 in model group and 5 in MAPK inhibitor group. In the MAPK inhibitor group and the model group, the model of pulpitis was prepared. After successful modeling, the MAPK inhibitor group was injected with SB203580 at a dose of 5 mg/kg from the jugular vein for 14 days. The MAPK inhibitor group was selected 14 days after modeling. Five rats in the model group were sacrificed at 3, 7 and 14 d after modeling, respectively. Their pulp tissue pathology, serum interleukin-6(IL-6), IL-8 content, p-p38MAPK, ERK, p-ERK, p38MAPK protein expression and p38MAPK, ERK mRNA expression were observed.RESULTS:Compared with the normal group, the length of apical damage, the width of the periapical periodontal membrane and the root necrosis rate of the first molar were significantly increased at 3, 7 and 14 days after modeling; while those in the MAPK inhibitor group were significantly lower(P<0.05). The levels of serum IL-6 and IL-8 in rats at 3, 7 and 14 days after modeling were significantly increased. Compared with 3, 7 and 14 days after modeling, serum IL-6 and IL-8 levels in rats with MAPK inhibitor group were significantly lower(P<0.05). Compared with the normal group, the expression of p-p38MAPK and p-ERK protein in the pulp tissue of the model group was increased. Compared with the model group, the MAPK inhibitor group The expression of p-p38MAPK and p-ERK protein in rat dental pulp tissue decreased(P<0.05).CONCLUSION: Activation of p38MAPK signaling pathway in dental pulp tissue of rats with chronic pulpitis increases the degree of inflammatory response, promotes disease progression, and inhibits p38MAPK signaling pathway, which can effectively reduce the expression of inflammatory factors.
AIM: To investigate the expression of p38MAPK signaling pathway in chronic pulpitis pain rats and its mechanism of action. METHODS: Twenty-five Wistar male rats of SPF grade were selected and divided into 3 groups, 5 in normal group, 15 in model group and 5 in MAPK inhibitor group. In the MAPK inhibitor group and the model group, the model of pulpitis was prepared. After successful modeling, the MAPK inhibitor group was injected with SB203580 at a dose of 5 mg/kg from the jugular vein for 14 days. The MAPK inhibitor group was selected 14 days after modeling. Five rats in the model group were sacrificed at 3, 7 and 14 d after modeling, respectively. Their pulp tissue pathology, serum interleukin-6(IL-6), IL-8 content, p-p38MAPK, ERK, p-ERK, p38MAPK protein expression and p38MAPK, ERK mRNA expression were observed.RESULTS:Compared with the normal group, the length of apical damage, the width of the periapical periodontal membrane and the root necrosis rate of the first molar were significantly increased at 3, 7 and 14 days after modeling; while those in the MAPK inhibitor group were significantly lower(P<0.05). The levels of serum IL-6 and IL-8 in rats at 3, 7 and 14 days after modeling were significantly increased. Compared with 3, 7 and 14 days after modeling, serum IL-6 and IL-8 levels in rats with MAPK inhibitor group were significantly lower(P<0.05). Compared with the normal group, the expression of p-p38MAPK and p-ERK protein in the pulp tissue of the model group was increased. Compared with the model group, the MAPK inhibitor group The expression of p-p38MAPK and p-ERK protein in rat dental pulp tissue decreased(P<0.05).CONCLUSION: Activation of p38MAPK signaling pathway in dental pulp tissue of rats with chronic pulpitis increases the degree of inflammatory response, promotes disease progression, and inhibits p38MAPK signaling pathway, which can effectively reduce the expression of inflammatory factors.
引文
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[13] 丁印浩,王倩,牛卫东,等.自噬相关蛋白LC3Av1和LC3B在大鼠牙髓炎中的表达研究[J].中国微生态学杂志,2017,29(2):130-132.
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[15] 林颖,秦伟,邹瑞,等.促丝裂原激活蛋白激酶在牙髓干细胞向成牙本质细胞分化和牙髓损伤修复中的作用[J].国际口腔医学杂志,2016,43(3):343-347.
[16] Feng YL,Yin YX,Ding J,et al.Alpha-1-antitrypsin suppresses oxidative stress in preeclampsia by inhibiting the p38MAPK signaling pathway:An in vivo and in vitro study[J].Plos One,2017,12(3):711-714.
[17] 徐万田,陈韵,林楠,等.TGF-β1调控ERK/MAPK信号通路对人牙髓细胞增殖和分化能力的影响研究[J].中国美容医学杂志,2018,27(4):94-97.
[18] Wang Y,Zhang J,Zhang L,et al.Adiponectin attenuates high glucose-induced apoptosis through the AMPK/p38MAPK signaling pathway in NRK-52E cells[J].Plos One,2017,12(5):215-218.
[19] 黄晓山,李菊,智丽媛,等.大鼠实验性牙髓炎组织中炎症信号血管粘附分子-1的表达及意义[J].成都医学院学报,2012,7(4):570-572.
[20] 陈霞,袁通穗,叶芳,等.牙髓炎不同阶段P2X受体家族在大鼠脑干中的表达变化研究[J].口腔医学研究,2016,32(10):1033-1037.
[2] Ma L,Wang SC,Tong J,et al.Activation and dynamic expression of Notch signalling in dental pulp cells after injury in vitro and in vivo[J].Int Endodo J,2016,49(12):1165-1174.
[3] 解用江,周琳.Toll样受体4在大鼠实验性牙髓炎和根尖周炎中的表达[J].牙体牙髓牙周病学杂志,2011,21(6):309-314.
[4] Saha SG,Jain S,Dubey S,et al.Effect of oral premedication on the efficacy of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis:A pospective,double-blind,randomized controlled clinical trial[J].J Clin Diagn Res,2016,10(2):25-28.
[5] 许国斌,张近波,张小乐,等.活化蛋白C经胞外信号调节激酶途径抑制肿瘤坏死因子-α介导的炎症反应[J].中国临床药理学杂志,2012,28(3):190-192.
[6] 高磊,栗红师,闫磊,等.大鼠实验性牙髓炎痛敏模型的建立及检验[J].牙体牙髓牙周病学杂志,2015,7(5):299-303.
[7] Yamasaki M,Kumazawa M,Kohsaka T,et al.Pulpal and periapical tissue reactions after experimental pulpal exposure in rats[J].J Compre Stomatol,2003,20(1):13-17.
[8] Raoof M,Ashrafganjoui E,Kooshki R,et al.Effect of chronic stress on capsaicin-induced dental nociception in a model of pulpitis in rats[J].Arch Oral Biol,2017,85(21):154-159.
[9] 李红,潘卫红.血红素氧合酶-1在大鼠牙髓炎中表达的实验研究[J].中华老年口腔医学杂志,2011,9(2):70-73.
[10] Yu SM,Stashenko P.Identification of inflammatory cells in developing rat periapical lesions[J].J Endod,1987,13(11):535-540.
[11] Stashenko P,Yu SM.T helper and T suppressor cell reversal during the development of induced rat periapical lesions[J].J Dent Res,1989,58(68):830-834.
[12] Bei Y,Tianqian H,Fanyuan Y,et al.ASH1L Suppresses matrix metalloproteinase through mitogen-activated protein kinase signaling pathway in pulpitis[J].J Endod,2016,43(2):306-314.
[13] 丁印浩,王倩,牛卫东,等.自噬相关蛋白LC3Av1和LC3B在大鼠牙髓炎中的表达研究[J].中国微生态学杂志,2017,29(2):130-132.
[14] 王雪纯.NOD1,NOD2和NLRP3炎症小体与牙髓炎[J].临床与病理杂志,2017,37(4):849-854.
[15] 林颖,秦伟,邹瑞,等.促丝裂原激活蛋白激酶在牙髓干细胞向成牙本质细胞分化和牙髓损伤修复中的作用[J].国际口腔医学杂志,2016,43(3):343-347.
[16] Feng YL,Yin YX,Ding J,et al.Alpha-1-antitrypsin suppresses oxidative stress in preeclampsia by inhibiting the p38MAPK signaling pathway:An in vivo and in vitro study[J].Plos One,2017,12(3):711-714.
[17] 徐万田,陈韵,林楠,等.TGF-β1调控ERK/MAPK信号通路对人牙髓细胞增殖和分化能力的影响研究[J].中国美容医学杂志,2018,27(4):94-97.
[18] Wang Y,Zhang J,Zhang L,et al.Adiponectin attenuates high glucose-induced apoptosis through the AMPK/p38MAPK signaling pathway in NRK-52E cells[J].Plos One,2017,12(5):215-218.
[19] 黄晓山,李菊,智丽媛,等.大鼠实验性牙髓炎组织中炎症信号血管粘附分子-1的表达及意义[J].成都医学院学报,2012,7(4):570-572.
[20] 陈霞,袁通穗,叶芳,等.牙髓炎不同阶段P2X受体家族在大鼠脑干中的表达变化研究[J].口腔医学研究,2016,32(10):1033-1037.