蜘蛛毒素口腔溃疡散对口腔溃疡模型大鼠的治疗作用及其机制研究
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篇名: 蜘蛛毒素口腔溃疡散对口腔溃疡模型大鼠的治疗作用及其机制研究
TITLE:
摘要: 目的:研究蜘蛛毒素口腔溃疡散对口腔溃疡(RAU)模型大鼠的治疗作用及其机制。方法:采用纸片扩散法检测该散剂的体外抑菌活性。取50只健康SD大鼠,随机分为正常组、模型组、阳性组(桂林西瓜霜,100 mg/kg)和口腔溃疡散高、低剂量组(70、35 mg/kg),每组10只。除正常组外,其余组大鼠均采用醋酸法在其右侧口腔黏膜建立RAU模型。模型成功建立后,各给药组大鼠分别以相应药物涂抹溃疡处,连续给药3 d;正常组和模型组不作处理。观察给药第1、3天时大鼠溃疡面情况并测定溃疡面积;取部分溃疡组织切片观察其组织形态学变化;检测大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1)、IL-6、干扰素γ(IFN-γ)的水平;采用免疫组化法检测大鼠溃疡组织中基质金属蛋白酶9(MMP-9)、核因子κB(NF-κB)、胱天蛋白酶3(Caspase-3)、多聚二磷酸腺苷核糖聚合酶(PARP)的蛋白表达水平。结果:口腔溃疡散体外抑菌效果明显。与空白组比较,模型组大鼠口腔溃疡明显,组织病变明显;血清中TNF-α、IL-1、IL-6、MDA水平均显著升高,IFN-γ、SOD、GSH水平均显著降低(P<0.01);溃疡组织中MMP-9、NF-κB、Caspase-3、PARP表达水平均显著升高(P<0.05或P<0.01)。与模型组比较,口腔溃疡散各剂量组大鼠的溃疡面积均显著缩小(P<0.05或P<0.01)或几近愈合,组织病变明显减轻;血清中MDA、TNF-α、IL-1、IL-6 水平均显著降低,SOD、GSH、IFN-γ水平均显著升高(P<0.05或P<0.01);溃疡组织中MMP-9、NF-κB、Caspase-3、PARP表达水平均显著降低(P<0.01)。结论:蜘蛛毒素口腔溃疡散具有强效的抑菌、消肿、修复作用,对RAU模型大鼠有明显的治疗作用;其机制可能与降低炎症因子水平、介导凋亡因子的表达、调节免疫失衡有关。
ABSTRACT: OBJECTIVE: To study therapeutic effects of Spider toxin oral ulcer powder on recurrent aphthous ulcer (RAU) model rats and its mechanism. METHODS: In vitro antimicrobial activity of the powder was determined by disk diffusion method. 50 healthy SD rats were randomly divided into normal group, model group, positive group (Guilin watermelon frost, 100 mg/kg) and oral ulcer powder high-dose and low-dose groups (70, 35 mg/kg), with 10 rats in each group. Except for normal group, RAU model was established in the right oral submucosa of rats in other groups by acetic acid method. After modeling, administration groups were smeared with corresponding drugs on ulcers for 3 days. Normal group and model group were not treated. The ulcer surface of rats was observed and the ulcer area was measured on the 1st and 3rd days after administration. The morphological changes of ulcer tissues were observed. The serum levels of SOD, MDA, GSH, TNF-α, IL-1, IL-6 and IFN-γ were detected. The protein expressions of MMP-9, NF-κB, Caspase-3 and PARP in ulcer tissues of rats were detected by immunohistochemistry. RESULTS: The oral ulcer powder showed obvious in vitro bacteriostasis effect. Compared with blank group, oral ulcer and histopathological changes were obvious in model group; serum levels of TNF-α, IL-1, IL-6 and MDA were increased significantly, while the levels of IFN-γ, SOD and GSH were decreased significantly (P<0.01); the expression of MMP-9, NF-κB, Caspase-3 and PARP in ulcer tissue were increased significantly (P<0.05 or P<0.01). Compared with model group, the ulcer area of rats in each dosage group was significantly reduced (P<0.05 or P<0.01) or nearly healed, the pathological changes of  tissue were significantly alleviated; serum levels of MDA, TNF-α, IL-1 and IL-6 were decreased significantly, while the levels of SOD, GSH and IFN-γ were increased significantly (P<0.05 or P<0.01); the expression of MMP-9, NF-κB, Caspase-3 and PARP in ulcer tissue were decreased significantly (P<0.01). CONCLUSIONS: Spider toxin oral ulcer powder shows strong bacteriostasis, detumescence and repair effects, and has obvious therapeutic effect on RAU model rats. Its mechanism may be related to reducing the level of inflammatory factors, mediating the expression of apoptotic factors and regulating immune imbalance.
期刊: 2019年第30卷第8期
作者: 邢国征,王长娜,田旭彤,唐佳美,张玉洁,乔晓强,周程艳
AUTHORS: XING Guozheng,WANG Changna,TIAN Xutong,TANG Jiamei,ZHANG Yujie,QIAO Xiaoqiang,ZHOU Chengyan
关键字: 口腔溃疡;蜘蛛毒素;口腔溃疡散;炎症因子;凋亡因子;免疫调节;机制;大鼠
KEYWORDS: Oral ulcer; Spider toxin; Oral ulcer powder; Inflammatory factor; Apoptosis factor; Immunoregulation; Mechanism; Rat
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