丹参片治疗口腔黏膜白斑及对局部组织金属基质蛋白酶-2、基质金属蛋白酶-9表达的影响
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摘要
目的:探讨丹参片治疗口腔黏膜白斑(OLK)的临床疗效及对局部组织细胞金属基质蛋白酶-2、9(MMP-2、MMP-9)表达的影响。方法:选取2014年5月至2016年3月南京中医药大学附属南京市中西医结合医院OLK患者136例,随机分为对照组与观察组,每组68例,同期进行口腔检查的20例健康人群作为健康对照组。对照组患者给予维甲酸和西瓜霜喷雾剂治疗,观察组则在对照组的基础上联合丹参片治疗。2个月为1个疗程,2组均连续治疗1个疗程,治疗后随访12个月。比较2组治疗后临床疗效,采用免疫组化法检测OLK患者及健康对照组局部黏膜组织中MMP-2、MMP-9表达情况。结果:治疗2个月后观察组总有效率为80.88%,显著高于对照组的63.24%(P<0.05);治疗4个月后观察组总有效率较治疗2个月后明显升高,且高于对照组(P<0.05)。与健康对照组比较,观察组局部黏膜组织中MMP-2和MMP-9阳性表达率明显升高(P<0.05);与治疗前比较,治疗2个月及4个月后观察组局部黏膜组织中MMP-2和MMP-9阳性表达率明显降低(P<0.05),且治疗4个月后观察组局部黏膜组织中MMP-2阳性表达率低于对照组(P<0.05);对照组仅治疗4个月后局部黏膜组织中MMP-2阳性表达率较治疗前降低(P<0.05)。2组随访期间观察组复发率明显低于对照组(P<0.05),2组癌变率差异无统计学意义(P>0.05)。结论:丹参片联合常规药物治疗OLK效果显著,可显著抑制局部组织MMP-2和MMP-9表达,并在短期内对抑制组织癌变具有一定的积极作用。
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.
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.
引文
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[13]冯欣,张须学,冯涛聚,等.丹参酮ⅡA亚微乳抗肿瘤作用及对逆转SMMC-7721/VCR肿瘤多药耐药的影响[J].中国临床药理学杂志,2017,33(5):427-430.
[14]贾铷,陈运转,祝伟.丹参川芎嗪对慢性阻塞性肺疾病合并呼吸衰竭患者肺功能、炎性反应因子的变化[J].世界中医药,2017,12(6):1361-1363,1367.
[15]赵雁焕,徐梅,陆洋.丹参注射液联合曲安奈德局部注射治疗OSF的疗效及对血清TGF-β1、IL-6的影响[J].海南医学院学报,2017,23(5):673-675,679.
[16]刘彩雲.Aurora A和ERK通路在口腔黏膜白斑及其恶变组织中表达差异的研究[D].大连:大连医科大学,2015.
[17]张红霞,李洪利.乳腺浸润性导管癌中PTTG与MMP-2和MMP-9的表达及相关性[J].中国生物化学与分子生物学报,2015,31(6):616-623.
[18]Min KW,Kim DH,Do SI,et al.Expression patterns of stromal MMP-2 and tumoural MMP-2 and-9 are significant prognostic factors in invasive ductal carcinoma of the breast[J].APMIS,2014,122(12):1196-1206.
[19]Desmeules P,Trudel D,Turcotte S,et al.Prognostic significance of TIMP-2,MMP-2,and MMP-9 on high-grade serous ovarian carcinoma using digital image analysis[J].Hum Pathol,2015,46(5):739-745.
[20]Yeh CB,Hsieh MJ,Hsieh YH,et al.Correction:Antimetastatic Effects of Norcantharidin on Hepatocellular Carcinoma by Transcriptional Inhibition of MMP-9 through Modulation of NF-k B Activity[J].PLo S One,2017,12(2):e0171900.
[2]李健,武彪,李映良.丹参酮ⅡA对人乳腺癌细胞MDA-MB-231作用的实验研究[J].军医进修学院学报,2012,33(7):754-756.
[3]余丽芳,章必成,刘健,等.丹参体外诱导人肝癌细胞Hep G2凋亡的初步研究[J].湖北中医药大学学报,2016,18(4):8-11.
[4]徐复国,梁锋,刘昌,等.丹参酮ⅡA磺酸钠联合氟尿嘧啶和亚叶酸钙对结直肠癌患者癌胚抗原的影响[J].中华临床医师杂志(连续型电子期刊),2015,9(11):2088-2091.
[5]Sun YS,Zhao Z,Zhu HP.Hispolon inhibits TPA-induced invasion by reducing MMP-9 expression through the NF-κB signaling pathway in MDA-MB-231 human breast cancer cells[J].Oncol Lett,2015,10(1):536-542.
[6]Sinanoglu A,Soluk-Tekkesin M,Olgac V.Cyclooxygenase-2 and Ki67Expression in Oral Leukoplakia:a Clinicopathological Study[J].J Oral Maxillofac Res,2015,6(2):e3.
[7]曹婕,金建秋,邓大君,等.白斑、扁平苔藓及口腔癌中人类乳头瘤病毒的检测[J].北京大学学报:医学版,2016,48(1):84-88.
[8]李月秀,肖长杰,杨娅.miRNA在稳定白斑和癌变白斑组织中表达的比较[J].社区医学杂志,2015,13(8):5-7.
[9]刘洋,邵轩,蔡锐,等.口腔非均质颗粒状白斑的中医治疗现状及研究进展[J].中西医结合心血管病电子杂志,2014,21(1):179-180.
[10]蔡鑫嘉,姚志刚,李龙,等.口腔白斑致病因素的研究进展[J].中华口腔医学研究杂志(连续型电子期刊),2017,11(2):111-114.
[11]胡莲.加味连术汤治疗口腔白斑33例[J].中国中医药现代远程教育,2013,11(5):17-18.
[12]董文杰,王禹锟,张诗扬.中西医结合治疗口腔白斑60例[J].中国中医药现代远程教育,2012,10(2):59.
[13]冯欣,张须学,冯涛聚,等.丹参酮ⅡA亚微乳抗肿瘤作用及对逆转SMMC-7721/VCR肿瘤多药耐药的影响[J].中国临床药理学杂志,2017,33(5):427-430.
[14]贾铷,陈运转,祝伟.丹参川芎嗪对慢性阻塞性肺疾病合并呼吸衰竭患者肺功能、炎性反应因子的变化[J].世界中医药,2017,12(6):1361-1363,1367.
[15]赵雁焕,徐梅,陆洋.丹参注射液联合曲安奈德局部注射治疗OSF的疗效及对血清TGF-β1、IL-6的影响[J].海南医学院学报,2017,23(5):673-675,679.
[16]刘彩雲.Aurora A和ERK通路在口腔黏膜白斑及其恶变组织中表达差异的研究[D].大连:大连医科大学,2015.
[17]张红霞,李洪利.乳腺浸润性导管癌中PTTG与MMP-2和MMP-9的表达及相关性[J].中国生物化学与分子生物学报,2015,31(6):616-623.
[18]Min KW,Kim DH,Do SI,et al.Expression patterns of stromal MMP-2 and tumoural MMP-2 and-9 are significant prognostic factors in invasive ductal carcinoma of the breast[J].APMIS,2014,122(12):1196-1206.
[19]Desmeules P,Trudel D,Turcotte S,et al.Prognostic significance of TIMP-2,MMP-2,and MMP-9 on high-grade serous ovarian carcinoma using digital image analysis[J].Hum Pathol,2015,46(5):739-745.
[20]Yeh CB,Hsieh MJ,Hsieh YH,et al.Correction:Antimetastatic Effects of Norcantharidin on Hepatocellular Carcinoma by Transcriptional Inhibition of MMP-9 through Modulation of NF-k B Activity[J].PLo S One,2017,12(2):e0171900.