弓 瑜 王 璐

高強(qiáng)度聚焦超聲對(duì)子宮肌瘤患者免疫功能的影響

弓 瑜 王 璐

目的比較高強(qiáng)度聚焦超聲(HIFU)和子宮肌瘤切除術(shù)(Myomectomy)對(duì)子宮肌瘤患者的免疫功能的影響。方法將子宮肌瘤患者80例，隨機(jī)分為HIFU組或Myo組。于入院時(shí)和術(shù)后24 h采集靜脈血樣，流式細(xì)胞術(shù)檢測(cè)患者CD4+、CD8+、CD4+/CD8+、NK細(xì)胞水平，酶聯(lián)免疫吸附法(ELISA)檢測(cè)患者血清IL-2，IL-6 和IL-10水平。結(jié)果HIFU組患者恢復(fù)快，術(shù)后并發(fā)癥較少，住院時(shí)間較短(P<0.05)。行HIFU術(shù)后患者CD4+T細(xì)胞、CD8+T細(xì)胞、CD4+/CD8+、NK細(xì)胞水平無顯著變化(P>0.05)；與之相反，手術(shù)切除后24 h，患者CD4+T細(xì)胞、CD8+T細(xì)胞、NK細(xì)胞水平均顯著下降(P<0.05),CD4+/CD8+比例也顯著下降(P<0.05)。治療后，兩組患者血清IL-6和IL-10水平均顯著升高，IL-2水平顯著降低；HIFU組患者IL-6和IL-10水平顯著低于Myo組，Myo組患者IL-2水平明顯高于HIFU組。結(jié)論HIFU對(duì)患者免疫功能影響較小，更好的免疫功能可能與組織創(chuàng)傷應(yīng)激減少有關(guān)，并有助于減少術(shù)后并發(fā)癥的發(fā)生。

高強(qiáng)度聚焦超聲；子宮肌瘤；免疫功能

手術(shù)創(chuàng)傷應(yīng)激可導(dǎo)致組織器官產(chǎn)生神經(jīng)、內(nèi)分泌、代謝及免疫功能的變化等一系列應(yīng)激反應(yīng)[1-2]，從而影響患者的預(yù)后和轉(zhuǎn)歸[3]，處理不當(dāng)會(huì)發(fā)生嚴(yán)重后果。手術(shù)技術(shù)的改進(jìn)導(dǎo)致微創(chuàng)手術(shù)替代傳統(tǒng)開放性手術(shù)。高強(qiáng)度聚焦超聲(HIFU)是1種新型微創(chuàng)技術(shù)，已廣泛用于治療子宮肌瘤[4]。HIFU可誘導(dǎo)目標(biāo)肌瘤完全凝固壞死，避免手術(shù)暴露[5]，有效地減輕了子宮肌瘤患者月經(jīng)過多，月經(jīng)延長，后背疼痛，盆腔不適和尿頻等癥狀。與傳統(tǒng)開放手術(shù)相比，行HIFU手術(shù)的患者恢復(fù)快，復(fù)發(fā)率低，預(yù)后更好[6]。本研究通過臨床試驗(yàn)，比較HIFU和手術(shù)切除對(duì)子宮肌瘤患者免疫功能及炎癥因子的影響。

1 資料與方法

1.1 病例資料

前瞻性納入2012年2月至2016年12月我院收治的子宮肌瘤患者80例，按奇偶數(shù)法隨機(jī)分為兩組。Myo組(n=40)行子宮肌瘤切除術(shù)；HIFU組(n=40)行高強(qiáng)度聚焦超聲。本研究由我院倫理委員會(huì)批準(zhǔn)實(shí)施，所有入組的患者均簽署了知情同意書。

1.2 入選標(biāo)準(zhǔn)

納入標(biāo)準(zhǔn)：①經(jīng)臨床檢查和超聲檢查確診為子宮肌瘤；②符合手術(shù)指征(異常子宮出血，盆腔區(qū)壓迫癥狀，反復(fù)妊娠丟失)[7]。排除標(biāo)準(zhǔn)：①合并陰道炎，盆腔炎，卵巢腫瘤和子宮內(nèi)膜異位癥等其它婦科疾病者；②結(jié)締組織病或曾用大劑量放射治療者；③麻醉禁忌征者。

1.3 治療方法

高強(qiáng)度聚焦超聲(HIFU):在超聲引導(dǎo)下，給予超聲消融治療(聚焦超聲腫瘤治療系統(tǒng)，重慶海扶醫(yī)療科技股份有限公司，國械注準(zhǔn)：20153230178)。患者取俯臥位，靜注瑞芬太尼50～400 μg和咪達(dá)唑侖1～4 mg鎮(zhèn)靜鎮(zhèn)痛，治療期間患者均保持清醒狀態(tài)?；叶茸兓癁镠IFU超聲消融導(dǎo)致靶腫瘤組織壞死，當(dāng)整個(gè)靶肌瘤灰度增加時(shí)停止治療。治療功率為300～400 w。手術(shù)切除(Myo):患者經(jīng)氣管插管和全身麻醉(初始：芬太尼0.02 mg，異丙酚100 mg，維庫溴銨：6 mg，咪達(dá)唑侖2 mg;維持：異丙酚6～10 mg/kg/h)，經(jīng)腹橫切口切除子宮肌瘤。

1.4 觀察指標(biāo)

所有患者于治療前后采外周血5 ml。免疫功能：流式細(xì)胞術(shù)檢測(cè)治療前后CD4+、CD8+、CD4+/CD8+、NK細(xì)胞水平。炎癥因子：酶聯(lián)免疫吸附法(ELISA)檢測(cè)治療前后IL-2，IL-6 和IL-10水平。不良反應(yīng)：術(shù)后患者不良反應(yīng)發(fā)生情況。

1.5 統(tǒng)計(jì)學(xué)方法

2 結(jié)果

2.1 患者一般資料及手術(shù)指標(biāo)比較

80例患者手術(shù)均順利完成。HIFU組與Myo組患者年齡、體質(zhì)指數(shù)、子宮體積、腫瘤體積的差異均無統(tǒng)計(jì)學(xué)意義(P>0.05)，兩組數(shù)據(jù)具有臨床可比性。HIFU組與Myo組在手術(shù)時(shí)間上無統(tǒng)計(jì)學(xué)差異，Myo組的平均術(shù)中出血量為100 ml，HIFU組術(shù)中出血量為0 ml。HIFU組的術(shù)后住院時(shí)間，日?；顒?dòng)恢復(fù)正常時(shí)間均顯著短于Myo組(P<0.05)。見表1。

表1 患者一般資料和手術(shù)指標(biāo)比較

2.2 HIFU和手術(shù)切除對(duì)患者免疫功能的影響

行HIFU術(shù)后患者CD4+T細(xì)胞、CD8+T細(xì)胞、CD4+/CD8+、NK細(xì)胞水平無顯著變化(P>0.05)；與之相反，手術(shù)切除后24 h，患者CD4+T細(xì)胞、CD8+T細(xì)胞、NK細(xì)胞水平均顯著下降(P<0.05),CD4+/CD8+比例也顯著下降(P<0.05)，且顯著低于HIFU組(P<0.05)。見表2。

表2 兩種方式對(duì)患者免疫功能的影響

注：與治療前比較，*為P<0.05；與治療后HIFU組比較，#為P<0.05。

2.3 HIFU和手術(shù)切除對(duì)患者炎癥因子的影響

治療后兩組患者血清IL-6和IL-10水平均顯著升高，HIFU組IL-6和IL-10水平顯著低于Myo組(P<0.05)；血清IL-2水平顯著降低，Myo組明顯高于HIFU組(P<0.05)。見表3。

表3 兩種手術(shù)方式對(duì)炎癥因子的影響

注：與治療前比較，*為P<0.05；與治療后HIFU組比較，#為P<0.05。

2.4 HIFU和手術(shù)切除不良反應(yīng)比較

HIFU組患者不良反應(yīng)發(fā)生率顯著低于Myo組(χ2=4.501,P=0.034)。兩組疼痛、便秘腹瀉發(fā)生率相比，差異無統(tǒng)計(jì)學(xué)意義(P>0.05)，陰道出血、嘔吐/腹脹等不良反應(yīng)發(fā)生率HIFU組明顯更低(P<0.05)。見表4。

表4 不良反應(yīng)發(fā)生情況比較(例，%)

3 討論

與開放的子宮肌瘤切除術(shù)比較，高強(qiáng)度聚焦超聲(HIFU)有恢復(fù)快，術(shù)后并發(fā)癥少，住院時(shí)間短等優(yōu)點(diǎn)，我們的研究也證實(shí)了這一點(diǎn)，這些結(jié)果可能與微創(chuàng)技術(shù)減少了創(chuàng)傷和對(duì)腹腔的影響有關(guān)[8]。此外，HIFU消融的腫瘤裂解物可激活人體的免疫系統(tǒng)，誘發(fā)特異性免疫反應(yīng)[9]。本研究中，與行常規(guī)切除術(shù)患者術(shù)后免疫功能相比，行HIFU患者特異和非特異免疫功能更好，具體表現(xiàn)為行HIFU術(shù)后患者免疫細(xì)胞百分比無顯著變化(P>0.05)，而手術(shù)切除后患者免疫細(xì)胞百分比顯著下降。這闡明了行HIFU患者術(shù)后并發(fā)癥較少的可能原因，也表明了HIFU治療潛在的抗腫瘤優(yōu)勢(shì)；因?yàn)镠IFU熱消融導(dǎo)致的全身免疫反應(yīng)對(duì)轉(zhuǎn)移性腫瘤的生長控制非常重要[10]。

Th1和Th2細(xì)胞是CD4+T淋巴細(xì)胞亞群，在體液免疫和細(xì)胞免疫調(diào)節(jié)中發(fā)揮重要作用。Th1細(xì)胞主要分泌干擾素-γ(IFN-γ)和IL-2，Th2細(xì)胞主要分泌IL-4，IL-6和IL-10。在生理?xiàng)l件下，機(jī)體會(huì)維持Th1/Th2亞群功能平衡。手術(shù)應(yīng)激誘使Th2型免疫應(yīng)答增加，導(dǎo)致體液免疫應(yīng)答增強(qiáng)，細(xì)胞免疫應(yīng)答減弱[11]。這與本研究結(jié)論一致：HIFU/手術(shù)切除后，兩組患者血清IL-6和IL-10均顯著升高；IL-2水平顯著降低。有文獻(xiàn)表明，IL-6的濃度與術(shù)后組織創(chuàng)傷程度成正比[12]，IL-6水平在術(shù)后早期不斷增加，誘導(dǎo)急性期反應(yīng)并上調(diào)IL-10[8]。這表明了無論哪一種手術(shù)方式，均會(huì)導(dǎo)致患者術(shù)后IL-6，IL-10同時(shí)增加。

綜上所述，我們證實(shí)了HIFU消融術(shù)后，患者特異和非特異性免疫功能更好，有利于降低患者圍手術(shù)期并發(fā)癥發(fā)生率。因此，在符合HIFU指征的條件下，HIFU應(yīng)成為治療子宮肌瘤的首選方式。

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InhibitoryEffectoftheSteroidSaponinsfromtheFlowersofCestrumNocturnum，Linn(SSFCN)onProliferationofLeukemiaK562CellsandPI3K/AKtPathwayRegulation

GONGYu,WANGLu.

WomenandInfantsHospitalofZhengzhou,Zhengzhou,450000

ObjectiveTo compare the effect of high-intensity focused ultrasound(HIFU) and conventional myomectomy on immune function in patients with uterine fibroids.Methods80 patients with uterine fibroids were divided into the HIFU or Myo group randomly.Venous blood samples were collected 24 h before and after operation.The percentages of CD4+and CD8+T cells and natural killer (NK) cells were quantified by flow cytometry (FCM).Serum levels of interleukin-2 (IL-2),IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay.ResultsHIFU was associated with earlier recovery,fewer post-operative complications,and shorter hospital stay (P<0.05).The levels of CD4+and CD8+T cells and NK cells in the HIFU group were not significantly altered after treatment compared with before treatment.In contrast,the levels of these cells in the Myo group decreased significantly after conventional myomectomy (P<0.05).The CD4+/CD8+T cell ratios also decreased significantly (P<0.05).Serum levels of IL-6 and IL-10 increased after treatment in both groups.IL-6 and IL-10 levels were significantly lower in the HIFU group than in the Myo group (P<0.05).In contrast,IL-2 level decreased significantly in the Myo group compared to the HIFU group(P<0.05).ConclusionHIFU treatment has little influence on immune functions.Better preserved immune function may reflect a reduction in tissue trauma after HIFU treatment and has less complications.

High-intensity focused ultrasound(HIFU);Uterine fibroids;Immune function

(ThePracticalJournalofCancer,2017,32:2067～2069)

450000 河南省鄭州市婦幼保健院(弓 瑜)；450000 鄭州大學(xué)第一附屬醫(yī)院(王 璐)

10.3969/j.issn.1001-5930.2017.12.047

R737.33

A

1001-5930(2017)12-2067-03

2017-06-09

2017-08-29)

(編輯：吳小紅)