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放射治疗的头颈癌患者全唾液中基质金属蛋白酶与pH值的关系。

The relationship between MMPs and pH in whole saliva of radiated head and neck cancer patients.

作者信息

Vuotila T, Ylikontiola L, Sorsa T, Luoto H, Hanemaaijer R, Salo T, Tjäderhane L

机构信息

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.

出版信息

J Oral Pathol Med. 2002 Jul;31(6):329-38. doi: 10.1034/j.1600-0714.2002.310603.x.

Abstract

BACKGROUND

Radiation therapy for head and neck tumour patients may lead to decreased salivary flow, oral mucosal lesions and increased caries experience. Salivary matrix metalloproteinases (MMPs) may participate in the pathogenesis of mucosal lesions and dentinal caries. The aims of this study were: (i) to assay the presence, molecular forms and proteolytic activity of MMP-8 (collagenase-2) and MMP-9 (gelatinase B) in the whole saliva of head and neck cancer patients having radiation therapy; (ii) to see whether salivary pH affects the activity of MMP-8 and MMP-9; and (iii) to find out the possible connection between MMP-8 and MMP-9 with the eruption of oral mucosal lesions during radiation therapy.

METHODS

The whole saliva samples of 39 head and neck cancer patients having radiation therapy were collected before, during and after radiation therapy, and saliva flow rate, pH, buffer capacity, Streptococcus mutans, Lactobacillus and Candida albicans were measured. Any oral mucosal lesions were examined during each visit. The levels of MMP-8 were measured by immunofluorometric assay (IFMA) and the presence of different MMP-8 forms was analysed using Western immunoblotting. The presence and molecular forms of MMP-9 were analyzed by gelatin zymography. MMP-9 capture activity assay was used to determine the APMA-activated MMP-9 activity (total) and the endogenously active MMP-9 (free activity).

RESULTS

Salivary flow rate, buffer capacity and pH decreased, and the levels of Lactobacilli increased significantly, during the first half of the radiation therapy. The endogenously activated salivary MMP-9 correlated with low salivary pH (P = 0.013). No connection was found between the oral mucosal lesions and salivary MMP-8 or MMP-9.

CONCLUSIONS

In this study, salivary MMP-8 or MMP-9 did not correlate with the presence of radiation induced oral mucosal lesions, but the activation of MMP-9 may be dependent on pH.

摘要

背景

对头颈部肿瘤患者进行放射治疗可能会导致唾液分泌减少、口腔黏膜损伤以及龋齿发生率增加。唾液基质金属蛋白酶(MMPs)可能参与黏膜损伤和牙本质龋齿的发病机制。本研究的目的是:(i)检测接受放射治疗的头颈部癌症患者全唾液中MMP-8(胶原酶-2)和MMP-9(明胶酶B)的存在情况、分子形式和蛋白水解活性;(ii)观察唾液pH值是否影响MMP-8和MMP-9的活性;(iii)找出MMP-8和MMP-9与放射治疗期间口腔黏膜损伤发生之间的可能联系。

方法

收集39例接受放射治疗的头颈部癌症患者在放疗前、放疗期间和放疗后的全唾液样本,测量唾液流速、pH值、缓冲能力、变形链球菌、乳酸杆菌和白色念珠菌。每次就诊时检查是否有口腔黏膜损伤。采用免疫荧光分析法(IFMA)测量MMP-8水平,并使用Western免疫印迹法分析不同MMP-8形式的存在情况。通过明胶酶谱法分析MMP-9的存在情况和分子形式。采用MMP-9捕获活性测定法测定APMA激活的MMP-9活性(总活性)和内源性活性MMP-9(游离活性)。

结果

在放射治疗的前半段,唾液流速、缓冲能力和pH值下降,乳酸杆菌水平显著升高。内源性激活的唾液MMP-9与低唾液pH值相关(P = 0.013)。未发现口腔黏膜损伤与唾液MMP-8或MMP-9之间存在联系。

结论

在本研究中,唾液MMP-8或MMP-9与放射诱导的口腔黏膜损伤的存在无关,但MMP-9的激活可能取决于pH值。

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