馮艷紅，張炳婕，師　帥，梁　漫，李　勤

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·臨床醫(yī)學(xué)·

槲皮素治療高危型人乳頭瘤病毒陽性的宮頸上皮內(nèi)瘤變患者30例療效觀察

馮艷紅，張炳婕，師帥，梁漫，李勤

[摘要]目的探討槲皮素治療高危型人乳頭瘤病毒(HPV)陽性感染的宮頸上皮內(nèi)瘤變I(CINⅠ)患者的臨床療效。方法選取2012年9月至2015年12月就診于陜西中醫(yī)藥大學(xué)第二附屬醫(yī)院婦科門診高危型HPV陽性的CINⅠ患者90例。按數(shù)字表法隨機(jī)分為3組：治療組用槲皮素3 g陰道給藥；陽性對(duì)照組用奧平栓6 g陰道給藥；空白對(duì)照組常規(guī)陰道擦洗。3組均每2 d給藥1次，連續(xù)2周為1個(gè)治療周期，治療3個(gè)周期。3個(gè)月后復(fù)查HPV、液基細(xì)胞，進(jìn)行病理檢查。結(jié)果治療組高危HPV轉(zhuǎn)陰22例，轉(zhuǎn)陰率73.3%；陽性對(duì)照組高危HPV轉(zhuǎn)陰21例，轉(zhuǎn)陰率70.0%；空白對(duì)照組高危HPV轉(zhuǎn)陰10例，轉(zhuǎn)陰率33.3%。治療組和陽性對(duì)照組治療后轉(zhuǎn)陰率高于空白對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。治療組液基細(xì)胞轉(zhuǎn)陰28例，轉(zhuǎn)陰率93.3%；陽性對(duì)照組液基細(xì)胞轉(zhuǎn)陰18例，轉(zhuǎn)陰率60.0%；空白對(duì)照組轉(zhuǎn)陰10例，轉(zhuǎn)陰率33.3%。治療組轉(zhuǎn)陰率顯著高于陽性對(duì)照組和空白組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。治療組病檢結(jié)果轉(zhuǎn)為正常21例，轉(zhuǎn)陰率70.0%；陽性對(duì)照組轉(zhuǎn)為正常19例，轉(zhuǎn)陰率63.3%；空白對(duì)照組轉(zhuǎn)為正常16例，轉(zhuǎn)陰率53.3%。治療組和陽性對(duì)照組治療后轉(zhuǎn)陰率高于空白組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論槲皮素治療HPV感染的CINⅠ患者，療效顯著，而且具有一定的抗炎作用。

[關(guān)鍵詞]槲皮素；人乳頭瘤病毒；宮頸上皮內(nèi)瘤變；對(duì)比研究

子宮頸病變是女性常見疾病，其中宮頸癌是女性最常見的生殖系統(tǒng)惡性腫瘤之一。研究證明，宮頸上皮內(nèi)瘤變(cervical intraepithelial neoplasia，CIN)是宮頸癌的癌前病變，持續(xù)感染高危型人乳頭瘤病毒(human papillomavirus，HPV)是導(dǎo)致CIN及宮頸癌最重要的致病因素[1]。宮頸癌發(fā)生及演變規(guī)律是：高危型HPV感染→高危型HPV持續(xù)感染→細(xì)胞分化→癌前病變(CIN)→原位癌→宮頸早期浸潤癌→宮頸浸潤癌。由于從感染高危型HPV到宮頸癌前病變到最后發(fā)展成為宮頸浸潤癌是一個(gè)相對(duì)比較長的病變過程，這給醫(yī)生和患者預(yù)防及治療提供了充足的時(shí)間。故宮頸癌的早期篩查及合理干預(yù)將取得明顯效果。每年定期婦科體檢，及早檢測、阻斷HPV感染對(duì)治療CIN及預(yù)防宮頸癌具有重要意義。所謂宮頸癌是可以預(yù)防、可以治愈的說法，其關(guān)鍵也在于此期的及時(shí)發(fā)現(xiàn)、及時(shí)診斷和正確處理[2]。我科使用槲皮素治療高危型HPV感染的CINⅠ患者多年，取得了較好的臨床效果?，F(xiàn)報(bào)道如下。

1資料與方法

1.1研究對(duì)象選自2012年9月至2015年12月就診于陜西中醫(yī)藥大學(xué)第二附屬醫(yī)院婦科門診并通過三階梯篩查的患者，納入年齡22～39歲，平均(31.23±3.02)歲，高危型HPV陽性的CINⅠ患者共90例。(1)納入標(biāo)準(zhǔn)：①HPV檢測結(jié)果為高危型HPV陽性；②液基細(xì)胞檢測提示有為未確定意義的不典型鱗狀細(xì)胞(ASCUS)；③病理結(jié)果為CINⅠ；④無子宮頸及子宮治療史和手術(shù)史；⑤患者自愿參加研究，簽署知情同意書。(2)排除標(biāo)準(zhǔn)：①不符合納入標(biāo)準(zhǔn)者；②合并急性生殖系統(tǒng)炎癥；③合并嚴(yán)重內(nèi)科疾??；④未婚、妊娠及哺乳期婦女；⑤HPV低危型或HPV陰性的患者；⑥病理確診為CINⅡ、CINⅡ以上及宮頸癌者。

1.2研究方法將90名高危型HPV陽性的CINⅠ患者，按數(shù)字表法隨機(jī)分為治療組、陽性對(duì)照組、空白對(duì)照組共3組，每組30例，3組患者之間年齡、孕產(chǎn)次等差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。月經(jīng)干凈3 d開始分組治療，治療組用中藥槲皮素3 g陰道給藥,陽性對(duì)照組用奧平栓6 g陰道給藥,空白對(duì)照組常規(guī)陰道擦洗清潔，3組均每2 d給藥1次, 連續(xù)2周為1個(gè)治療周期,治療3個(gè)周期。3個(gè)月后復(fù)查HPV、液基細(xì)胞, 進(jìn)行病理檢查。在治療期間禁止盆浴、性生活；月經(jīng)期停止用藥。

1.3評(píng)定標(biāo)準(zhǔn)治療后3個(gè)月復(fù)查：高危型HPV轉(zhuǎn)陰即為有效，高危型HPV陽性則為無效；液基細(xì)胞轉(zhuǎn)為正常為有效，沒有改變?yōu)闊o效；病理檢查轉(zhuǎn)為正常為有效，沒有改變?yōu)闊o效。

1.4統(tǒng)計(jì)學(xué)處理數(shù)據(jù)分析采用SPSS 13.0統(tǒng)計(jì)軟件，采用χ2檢驗(yàn)，P<0.05為差異具有統(tǒng)計(jì)學(xué)意義。

2結(jié)果

2.1HPV檢測治療組和陽性對(duì)照組高危型HPV轉(zhuǎn)陰率均高于空白組，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見表1。

表1　3組患者治療后人乳頭瘤病毒結(jié)果比較

注：與空白對(duì)照組比較aP<0.05

2.2液基細(xì)胞檢測液基細(xì)胞檢測結(jié)果顯示，治療前CINⅠ患者液基細(xì)胞示有未確定意義的不典型鱗狀細(xì)胞(ASCUS)，且有輕度炎癥(圖1a)。采用槲皮素治療后，患者組織中未見未確定意義的不典型鱗狀細(xì)胞，趨于正常(圖1b)。

注：A為治療前；B為治療后。CIN：宮頸上皮內(nèi)瘤變圖1　治療組治療前后CINⅠ患者液基細(xì)胞檢測結(jié)果

統(tǒng)計(jì)結(jié)果表明：槲皮素治療后液基細(xì)胞轉(zhuǎn)陰率顯著高于陽性和空白對(duì)照組(P<0.05)。見表2。

表2　3組患者治療后液基細(xì)胞學(xué)轉(zhuǎn)陰結(jié)果比較(例)

注：與陽性對(duì)照組和空白對(duì)照組比較aP<0.05

2.3病理檢測病理檢測結(jié)果顯示，治療前CINⅠ患者可見異型細(xì)胞。采用槲皮素治療后，患者組織中幾乎未見異型細(xì)胞，趨于正常。見圖2。

注：A為治療前；B為治療后。CIN：宮頸上皮內(nèi)瘤變圖2　治療組治療前后CINⅠ患者組織病理圖

統(tǒng)計(jì)結(jié)果表明：治療組和陽性對(duì)照組轉(zhuǎn)陰率均高于空白組(P<0.05)。見表3。

表3　3組患者治療后病理檢測結(jié)果比較(例)

注：與空白對(duì)照組比較aP<0.05

3討論

CIN常發(fā)生于25～35歲婦女，是一組與子宮頸浸潤癌密切相關(guān)的子宮頸病變，約60%的CINⅠ會(huì)自然消退[2]。正常的宮頸從持續(xù)感染高危型HPV后到CIN再進(jìn)一步進(jìn)展為宮頸癌是個(gè)連續(xù)的過程，一般需要8～10年的時(shí)間，每1例CIN都有進(jìn)一步惡變發(fā)展的可能性，CINⅠ、CINⅡ和CINⅢ發(fā)展為浸潤癌的危險(xiǎn)分別為15%、30%和45%[3]。雖然部分患者不經(jīng)治療病變可自然消退或逆轉(zhuǎn)，但HPV陽性婦女在隨訪中診斷CINⅠ可能性是初次HPV陰性婦女的3.8倍，發(fā)展為CINⅡ和CINⅢ的可能性是HPV陰性婦女的12.7倍。故對(duì)CINⅠ高危型HPV陽性的患者早期發(fā)現(xiàn)、早期診斷和早期治療就尤為重要。且CIN發(fā)展成為浸潤癌為正常情況的7倍，這就要求對(duì)CIN予以更高的重視和正確、及時(shí)的處理。

槲皮素是一種中藥，它具有抗病毒、抗腫瘤、抗炎、抗氧化等多種生物活性[4]，本研究使用的槲皮素由本院藥劑科購進(jìn)并加工。通過本研究可認(rèn)為，中藥槲皮素治療高危型HPV陽性的CINⅠ患者取得滿意療效，其可以通過控制高危型HPV感染，阻斷宮頸病變的發(fā)生發(fā)展，而有效降低宮頸癌的發(fā)生率。因該研究樣本量較少，其抗HPV和抗炎機(jī)制有待進(jìn)一步深入研究。

[參考文獻(xiàn)]

[1]郎景和. 子宮頸癌預(yù)防的現(xiàn)代策略[J]. 中國醫(yī)學(xué)科學(xué)院學(xué)報(bào), 2007, 29(5):575-578.

[2]謝幸.婦產(chǎn)科學(xué)[M]. 8版.北京：人民衛(wèi)生出版社,2013：301-304.

[3]曹澤毅.中華婦產(chǎn)科學(xué) [M]. 2版.北京:人民衛(wèi)生出版社,1999：2012-2028.

[4]舒毅，譚陶，張思宇，等.槲皮素的藥理學(xué)研究進(jìn)展[J].華西藥學(xué)雜志,2008,23(6):689-691.

(本文編輯：甘輝亮)

Clinical effects of quercetin in the treatment of 30 patients with high-risk type HPV positive CIN

Feng Yanhong, Zhang Bingjie, Shi Shuai, Liang Man, Li Qin

(Second Affiliated Hospital, Shanxi University of Chinese Medicine, Xianyang 712000,China)

[Abstract]ObjectiveTo investigate the clinical effects of quercetin in the treatment of patients with high-risk type human papillomavirus (HPV) positive cervical intraepithelial neoplasia (CIN).Methods Ninety patients with HPV positive CIN hospitalized in the Outpatient Department of Gynecology, Second Affiliated Hospital, Shanxi Chinese Pharmacological University, from September 2012 to December 2015 were selected for the study. The patients were equally divided into 3 groups: the treatment group, the positive control group and the blank control group. The treatment group received medication of 3 g quercetin by the way of vagina. The positive control group was given 6 g Opin (plug) also by the way of vagina, and the blank control group had routine cleansing of vagina. The patients of the 3 groups received treatment once every other day, for a succession of 2 weeks, with 2 weeks as a treatment course, and with a total of 3 treatment courses. Three months later, the patients were reexamined on HPV and fluid-based cells, and had pathological examination as well.ResultsTwenty-two patients with high-risk type HPV in the treatment group turned negative, with the negative-turning rate of 73.3%, while 21 patients with high-risk type HPV in the positive control group turned negative, with the negative-turning rate of 70.0%, and 17 patients in the blank control group turned negative, with the negative-turning rate of 33.3%. Following treatment, the negative-turning rates of the treatment group and the positive control group were higher than that of the negative control group(P<0.05). With regard to fluid-based cells, 28 patients in the treatment group turned negative, with the negative-turning rate of 93.3%. On the other hand, there were 18 patients in the positive control group that turned negative, with the negative-turning rate of 60.0%; and there were only 10 patients in the blank control group that turned negative, with the negative-turning rate of 33.3%. The negative-turning rate of the treatment group was significantly higher than those of the positive control group and the blank control group(P<0.05). With regard to pathological detection results, 21 patients in the treatment group turned negative, with the negative-turning rate of 70.0%, 19 patients in the positive control group turned negative, with the negative-turning rate of 63.3%, while in the blank control group, there were only 16 patients that turned negative, with the negative-turning rate of 53.3%. The negative-turning rates of the treatment group and the positive control group after treatment were higher than that of the blank control group, and statistical significance could be seen when comparisons were made between them(P<0.05).ConclusionQuercetin could produce significant therapeutic effects on the CIN patients infected with HPV, and it also turned out to have certain anti-inflammatory effect.

[Key words]Quercetin; Human papillomavirus; Cervical intraepithelial neoplasia; Comparative study

(收稿日期：2015-09-15)

[中圖分類號(hào)]R737.33

[文獻(xiàn)標(biāo)識(shí)碼]A[DOI]10.3969/j.issn.1009-0754.2016.02.018

[通信作者]李勤，電子信箱：liqin9800@163.com

[基金項(xiàng)目]陜西省教育廳專項(xiàng)科研計(jì)劃項(xiàng)目(12JK0779)

·論著·

[作者單位]712000陜西 咸陽，陜西中醫(yī)藥大學(xué)第二附屬醫(yī)院