首页|6-姜酚基于PKB/KIF14信号通路对大鼠口腔黏膜愈合的作用

6-姜酚基于PKB/KIF14信号通路对大鼠口腔黏膜愈合的作用

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目的 探讨生姜提取物6-姜酚对实验性口腔溃疡大鼠黏膜愈合的促进作用,及其对蛋白激酶B(PKB)/驱动蛋白家族成员14(KIF14)信号通路的调节作用。方法 将50只大鼠随机分为正常组、模型组、6-姜酚组、信号通路抑制剂(LY294002)组和LY294002联合6-姜酚组,每组10只,除正常组外,其余组大鼠用冰醋酸烧灼法建立口腔溃疡模型,6-姜酚组大鼠尾静脉注射6-姜酚6mg·kg-1,LY294002 组大鼠尾静脉注射 LY294002 0。3 mg·kg-1,LY294002 联合 6-姜酚组大鼠尾静脉注射 LY294002 0。3mg·kg-1,30min后,尾静脉注射6-姜酚6mg·kg-1;每日1次,连续7d。计算溃疡面积,HE染色观察病理学变化,酶联免疫吸附试验(ELISA)检测白细胞介素-6(interleukin 6,IL-6)、白细胞介素-1β(interleukin 1β,IL-1β)和肿瘤坏死因子-α(tumor necrosis factor α,TNF-α)水平,实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)检测基质金属蛋白酶2(matrix metal-loproteinase 2,MMP-2)和基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)水平,蛋白印迹法(Western blotting)检测磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase,PI3K)、PKB和KIF14蛋白的相对表达量。结果 模型组大量炎性细胞浸润,黏膜上皮细胞坏死脱落,无新生成纤维细胞;6-姜酚组黏膜上皮覆盖,溃疡趋于愈合;LY294002组大量炎性细胞浸润,上皮结构被破坏,黏膜上皮细胞脱落坏死;LY294002联合6-姜酚组炎性细胞浸润减少,病变较6-姜酚组减轻。与模型组比较,6-姜酚组大鼠溃疡面积减小,IL-6、TNF-α、IL-1β水平及MMP-2、MMP-9 mRNA的相对表达量降低,p-PI3K、p-PKB以及KIF14的相对表达量升高;LY294002组溃疡面积增加,IL-6、TNF-α、IL-1β水平以及MMP-2、MMP-9 mRNA的相对表达量升高,p-PI3K、p-PKB及KIF14的相对表达量降低(P<0。05);与LY294002联合6-姜酚组比较,6-姜酚组大鼠溃疡面积减小,IL-6、TNF-α、IL-1β水平及MMP-2、MMP-9 mRNA的相对表达量降低,p-PI3K、p-PKB及KIF14的相对表达量升高;LY294002组溃疡面积增加,IL-6、TNF-α、IL-1β水平及MMP-2、MMP-9mRNA相对表达量升高,p-PI3K、p-PKB及KIF14的相对表达量降低(P<0。05)。结论 生姜提取物6-姜酚可促进口腔溃疡大鼠创面愈合,其可能是通过激活蛋白激酶B/驱动蛋白家族成员14信号通路发挥作用的。
6-Gingerol promoting the oral mucosal healing in rats based on PKB/KIF14 signaling pathway
Objective To explore the promoting effect of 6-gingerol extract on mucosal healing in experimental oral ulcer rats and the regulation of protein kinase B(PKB)/driver protein family member 14(KIF14)signaling pathway.Methods Fifty rats were ran-domly divided into normal group,model group,6-gingerol group,LY294002 group and LY294002 combined with 6-gingerol group.Except for the normal group,the other groups were used to establish oral ulcer model by glacial acetic acid cauterization.Rats in the 6-gingerol group were injected with 6-gingerol 6 mg·kg-1,rats in the LY294002 group were injected with LY294002 0.3 mg·kg-1,rats in the LY294002 combined with 6-gingerol group were injected with LY294002 0.3 mg·kg-1,and rats in the 6-gingerol combined with 6-gingerol group were injected with LY294002 0.3 mg·kg-1 for 30 minutes,then tail vein injection of 6-gingerol 6 mg·kg-1,once a day,for 7 consecutive days.The ulcer area was calculated,the pathological changes were observed by HE staining,the inter-leukin 6(IL-6),interleukin 1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme linked immunosorbent assay(ELISA),and the matrix metalloproteinase 2(MMP-2)and MMP-9 were detected by quantitative real-time polymerase chain reac-tion(qRT-PCR).The relative expression levels of phosphatidylinositol 3 kinase(PI3K),PKB and KIF14 proteins were detected by Western blotting.Results In the model group,a large number of inflammatory cells infiltrated the mucosa and the epithelial cells were necrotic and shed,and no new fibrocytes were formed.In 6-gingerol group,mucosal epithelium was covered and ulcer tended to heal.In LY294002 group,a large number of inflammatory cells were infiltrated,the epithelial structure was destroyed,and the mucosal epithelial cells were shed and necrotic.The inflammatory cell infiltration in LY294002 combined with 6-gingerol group was reduced,and the pathological changes were reduced in 6-gingerol group.Compared with model group,the ulcer area in 6-gingerol group was decreased,the levels of IL-6,TNF-α and IL-1β,the relative expression levels of MMP-2 and MMP-9 mRNA decreased,the relative expression levels of p-PI3K,p-PKB and KIF14 increased,and the ulcer area in LY294002 group increased.The levels of IL-6,TNF-α and IL-1β were increased,the relative expression levels of MMP-2 and MMP-9 mRNA increased,and the relative ex-pression levels of p-PI3K,p-PKB and KIF14 decreased(P<0.05).Compared with LY294002 combined with 6-gingerol group,the ulcer area of 6-gingerol group was decreased,the levels of IL-6,TNF-α and IL-1β,the relative expression levels of MMP-2 and MMP-9 mRNA decreased,the relative expression levels of p-PI3K,p-PKB and KIF14 increased,and the ulcer area of LY294002 group increased.The levels of IL-6,TNF-α and IL-1β were increased,the relative expression levels of MMP-2 and MMP-9 mRNA increased,and the relative expression levels of p-PI3K,p-PKB and KIF14 decreased(P<0.05).Conclusion 6-Gingerol,a ginger extract,can promote wound healing in rats with oral ulcer,possibly through activating PKB/KIF14 signaling pathway.

6-gingerol(a ginger extract)oral ulcerPKB/KIF14 signaling pathway

张先琴、陈营杰、张睿

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郑州市口腔医院口腔修复科,郑州 450000

6-姜酚(生姜提取物) 口腔溃疡 蛋白激酶B/驱动蛋白家族成员14信号通路

河南省医学科技攻关计划

LHCJ20191151

2024

西北药学杂志
西安交通大学,陕西省药学会

西北药学杂志

CSTPCD
影响因子:0.912
ISSN:1004-2407
年,卷(期):2024.39(2)
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