丹參片治療口腔黏膜白斑及對局部組織金屬基質(zhì)蛋白酶—2、基質(zhì)金屬蛋白酶—9表達(dá)的影響

朱鵬君　鄒桂梅　汪銘

摘要 目的：探討丹參片治療口腔黏膜白斑（OLK）的臨床療效及對局部組織細(xì)胞金屬基質(zhì)蛋白酶-2、9（MMP-2、MMP-9）表達(dá)的影響。方法：選取2014年5月至2016年3月南京中醫(yī)藥大學(xué)附屬南京市中西醫(yī)結(jié)合醫(yī)院OLK患者136例，隨機(jī)分為對照組與觀察組，每組68例，同期進(jìn)行口腔檢查的20例健康人群作為健康對照組。對照組患者給予維甲酸和西瓜霜噴霧劑治療，觀察組則在對照組的基礎(chǔ)上聯(lián)合丹參片治療。2個(gè)月為1個(gè)療程，2組均連續(xù)治療1個(gè)療程，治療后隨訪12個(gè)月。比較2組治療后臨床療效，采用免疫組化法檢測OLK患者及健康對照組局部黏膜組織中MMP-2、MMP-9表達(dá)情況。結(jié)果：治療2個(gè)月后觀察組總有效率為80.88%，顯著高于對照組的63.24%（P<0.05）；治療4個(gè)月后觀察組總有效率較治療2個(gè)月后明顯升高，且高于對照組（P<0.05）。與健康對照組比較，觀察組局部黏膜組織中MMP-2和MMP-9陽性表達(dá)率明顯升高（P<0.05）；與治療前比較，治療2個(gè)月及4個(gè)月后觀察組局部黏膜組織中MMP-2和MMP-9陽性表達(dá)率明顯降低（P<0.05），且治療4個(gè)月后觀察組局部黏膜組織中MMP-2陽性表達(dá)率低于對照組（P<0.05）；對照組僅治療4個(gè)月后局部黏膜組織中MMP-2陽性表達(dá)率較治療前降低（P<0.05）。2組隨訪期間觀察組復(fù)發(fā)率明顯低于對照組（P<0.05），2組癌變率差異無統(tǒng)計(jì)學(xué)意義（P>0.05）。結(jié)論：丹參片聯(lián)合常規(guī)藥物治療OLK效果顯著，可顯著抑制局部組織MMP-2和MMP-9表達(dá)，并在短期內(nèi)對抑制組織癌變具有一定的積極作用。

關(guān)鍵詞 口腔黏膜白斑；丹參片；金屬基質(zhì)蛋白酶

Abstract Objective：To explore the clinical efficacy of Danshen Tablet on oral leukoplakia （OLK） and its effects on the expression of metal matrix protease-2，9 （MMP-2 and MMP-9） in local tissues.Methods：A total of 136 patients with OLK treated in Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Traditional Chinese Medicine from May 2014 to March 2016 were selected and randomly divided into control group and observation group，with 68 cases in each group，and 20 cases of healthy people were chosen in the same period as healthy control group.The patients in the control group were treated with retinoic acid and watermelon frost spray，and the observation group was treated with Danshen Tablet on the basis of the same treatment.Both groups were treated for 1 course （2 months as a course） and followed up for 12 months after treatment.The clinical effects of the 2 groups were compared and the expressions of MMP-2 and MMP-9 in local mucosa of OLK patients and healthy controls were detected by immunohistochemistry.Results：After 2 months treatment，the total effective rate of the observation group was 80.88%，which was significantly higher than 63.24% of the control group （P<0.05）.After 4 months′ treatment，compared with 2 months treatment，the total effective rate in the observation group was significantly increased which was higher than the control group （P<0.05）.Compared with the healthy control group，the positive expression rates of MMP-2 and MMP-9 in the local mucosa tissues of OLK patients were significantly increased （P<0.01），and the positive expression rates of MMP-2 and MMP-9 in the local mucosa tissues in the observation group decreased more significantly after 2 months and 4 months treatment than before treatment （P<0.05 or P<0.01）.The positive expression rate of MMP-2 in the local mucosa tissues of observation group was decreased more than control group （P<0.05），and the positive expression rate of MMP-2 in local mucosa tissues of the control group 4 months after treatment decreased more significantly than that before treatment （P<0.05）.The recurrence rate of the observation group decreased more significantly than that of the control group during the follow-up period （P<0.05），and there was no significant difference in cancer rate between the 2 groups （P>0.05）.Conclusion：The combination of Danshen Tablets and conventional drugs have significant effects on OLK.It can significantly inhibit the expression of MMP-2 and MMP-9 in local tissues，which has a positive effect on the inhibition of tissue cancer in the short term.

Key Words Oral leukoplakia； Danshen Tablets； Metal matrix protease

中圖分類號：R289.5；R751文獻(xiàn)標(biāo)識碼：Adoi：10.3969/j.issn.1673-7202.2018.09.020

口腔黏膜白斑病（OLK）發(fā)病機(jī)制復(fù)雜，與內(nèi)分泌功能紊亂、維生素缺乏、霉菌感染及局部持續(xù)性機(jī)械刺激等導(dǎo)致口腔黏膜上皮過度角化等有關(guān)，患者可于頰、舌、唇等部位黏膜上出現(xiàn)灰白色或乳白色斑狀病變，隨著疾病進(jìn)展病變部位可逐漸增大、變厚及變粗糙。口服維生素、冷凍及手術(shù)治療可改善OLK患者臨床癥狀。但有研究顯示，OLK癌變率為3%～5%，單純對癥治療無法有效控制其癌前病變[1]。研究顯示，丹參主要有效成分丹參酮可抑制肝癌細(xì)胞、乳腺癌細(xì)胞及結(jié)直腸癌細(xì)胞等的體外增殖，具有明顯的抑制腫瘤細(xì)胞凋亡的作用[2-4]。……