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      巨泌乳素檢測(cè)在女性住院精神分裂癥患者中的意義

      2020-12-23 04:35:57陳海支費(fèi)小聰王振華沈曄雷禮磊趙徐東曾雷任麗華
      關(guān)鍵詞:利培酮泌乳素精神分裂癥

      陳海支 費(fèi)小聰 王振華 沈曄 雷禮磊 趙徐東 曾雷 任麗華

      [摘要] 目的 探討巨泌乳素(MPRL)檢測(cè)在女性住院精神分裂癥患者中的意義。 方法 收集2018年1月-2019年6月浙江省湖州市第三人民醫(yī)院精神科住院的65例精神分裂癥患者,常規(guī)使用利培酮片治療。在治療過程中記錄患者月經(jīng)情況,并于治療前、治療后第6周末分別用發(fā)光免疫分析與酶聯(lián)免疫吸附測(cè)定法檢測(cè)泌乳素(PRL)和MPRL含量。應(yīng)用前后自身對(duì)照研究對(duì)治療前后PRL及MPRL含量進(jìn)行比較,同時(shí)根據(jù)第6周末PRL及MPRL含量將65例患者劃分為PRL正常組16例、高PRL血癥組49例,將高PRL血癥組再分為MPRL血癥組21例、非MPRL血癥組28例,并對(duì)不同組月經(jīng)延遲情況進(jìn)行比較。 結(jié)果 65例患者治療后PRL及MPRL水平較治療前明顯升高,差異均有高度統(tǒng)計(jì)學(xué)意義(均P < 0.01)。PRL正常組、高PRL血癥組、MPRL血癥組及非MPRL血癥組出現(xiàn)的月經(jīng)延遲數(shù)及發(fā)生率分別是2例(12.5%)、30例(61.2%)、5例(23.8%)及25例(89.3%)。四組月經(jīng)延遲發(fā)生率兩兩比較,MPRL血癥組與PRL正常組比較,差異無統(tǒng)計(jì)學(xué)意義(P > 0.05),非MPRL血癥組月經(jīng)延遲發(fā)生率分別高于高PRL血癥組、MPRL血癥組及PRL正常組,差異有高度統(tǒng)計(jì)學(xué)意義(均P < 0.01),高PRL血癥組月經(jīng)延遲發(fā)生率高于MPRL血癥組及PRL正常組,差異有高度統(tǒng)計(jì)學(xué)意義(均P < 0.01)。 結(jié)論 利培酮所致MPRL血癥可能不會(huì)導(dǎo)致患者月經(jīng)延遲,臨床上檢測(cè)MPRL有利于指導(dǎo)高PRL血癥的治療。

      [關(guān)鍵詞] 利培酮;精神分裂癥;泌乳素;巨泌乳素;月經(jīng)延遲

      [中圖分類號(hào)] R749.3? ? ? ? ? [文獻(xiàn)標(biāo)識(shí)碼] A? ? ? ? ? [文章編號(hào)] 1673-7210(2020)10(a)-0105-04

      Significance of macroprolactin detection in the female inpatients with schizophrenia

      CHEN Haizhi1? ?FEI Xiaocong1? ?WANG Zhenhua1? ?SHEN Ye2? ?LEI Lilei1? ?ZHAO Xudong1? ?ZENG Lei1? ?REN Lihua1

      1.Department of Psychiatry, the Third People′s Hospital of Huzhou City, Zhejiang Province, Huzhou? ?313000, China; 2.Clinical Laboratory, the Third People′s Hospital of Huzhou City, Zhejiang Province, Huzhou? ?313000, China

      [Abstract] Objective To explore the significance of macroprolactin (MPRL) detection in the female inpatients with schizophrenia. Methods From January 2018 to June 2019, 65 schizophrenics patients were collected in Department of Psychiatry, the Third People′s Hospital of Huzhou City, Zhejiang Province and all of them were treated with Risperidone Tablets. The menstrual situation of the patients was recorded during the treatment, and the contents of prolactin (PRL) and MPRL were measured by luminescent immunoassay and enzyme-linked immunosorbent assay respectively before and at the end of the sixth weekend of the treatment. The content of PRL and MPRL were compared by self-control study before and after the treatment, at the same time, according to the content of PRL and MPRL at the end of the sixth weekend, 65 patients were divided into the normal PRL group (16 cases) and the hyperprolactinemia group (49 cases). The hyperprolactinemia group was then divided into the macroprolactinemia group (21 cases) and the non-macroprolactinemia group (28 cases), and the menstrual delay in different groups was compared. Results The levels of PRL and MPRL in 65 patients after treatment were significantly increased compared with those before treatment, and the differences were highly statistically significant (all P < 0.01). The number and incidence of menstrual delay of the normal PRL group , the hyperprolactinemia group, the macroprolactinemia group and the non-macroprolactinemia group were 2 cases (12.5%), 30 cases (61.2%), 5 cases (23.8%) and 25 cases (89.3%), respectively. The incidence of menstrual delay in four groups was compared in pairs, there was no significant difference between the macroprolactinemia group and the normal PRL group (P > 0.05), the incidence of menstrual delay in the non-macroprolactinemia group was higher than that in the hyperprolactinemia group, the macroprolactinemia group and the normal PRL group, with highly statistically significant differences (all P < 0.01). The incidence of menstrual delay in the hyperprolactinemia group was higher than that in the macroprolactinemia group and normal PRL group, with highly statistically significant differences (all P < 0.01). Conclusion Macroprolactinemia caused by Risperidone may not lead to menstrual delay. The clinical detection of macroprolactin is helpful to guide the treatment of hyperprolactinemia.

      [Key words] Risperidone; Schizophrenia; Prolactin; Macroprolactin; Menstrual delay

      抗精神病藥物往往會(huì)引起泌乳素(PRL)水平增高,導(dǎo)致女性患者月經(jīng)延遲,甚至閉經(jīng)等一系列問題[1-3],影響患者生活質(zhì)量使患者服藥的依從性下降[4-5]。臨床發(fā)現(xiàn)同樣抗精神病藥物,也只有67%患者出現(xiàn)PRL水平增高,在這些患者中并不是所有的均會(huì)出現(xiàn)月經(jīng)延遲或者閉經(jīng)[1,6-7],這可能與PRL中一種無活性的巨泌乳素(MPRL)有關(guān)[7]。為此,本課題組進(jìn)行了本研究,現(xiàn)將結(jié)果報(bào)道如下:

      1 資料與方法

      1.1 一般資料

      所有病例均來自2018年1月—2019年6月浙江省湖州市第三人民醫(yī)院(以下簡(jiǎn)稱“我院”)住院精神分裂癥患者。共收集65例女性患者,年齡18~45歲,平均(32.80±5.75)歲;婚姻狀況:已婚42例,未婚23例;病程3~48個(gè)月,平均(7.0±25.0)個(gè)月;利培酮?jiǎng)┝?~5 mg/d,平均(3.50±0.84)mg/d。本項(xiàng)目獲得我院醫(yī)學(xué)倫理委員會(huì)審批通過,并且所有研究對(duì)象監(jiān)護(hù)人簽署了知情同意書。

      納入標(biāo)準(zhǔn):①符合《精神疾病診斷與統(tǒng)計(jì)手冊(cè)第五版》(DSM-V)[8]精神分裂癥診斷標(biāo)準(zhǔn);②陽(yáng)性和陰性癥狀量表(PANSS)總分≥60分[9];③入院前半年內(nèi)月經(jīng)規(guī)律且月經(jīng)周期在28~30 d之間。排除標(biāo)準(zhǔn):①有心、肝、腎、內(nèi)分泌、神經(jīng)系統(tǒng)疾病;②無酒精依賴及其他精神活性物質(zhì)濫用者;③高過敏體質(zhì)者;④實(shí)驗(yàn)室檢查指標(biāo)超過正常值2倍以上且有臨床意義;⑤6個(gè)月內(nèi)接受抗精神病藥治療。

      1.2 方法

      患者入院后首日使用抗精神病藥物利培酮片1 mg口服(西安楊森制藥有限公司,批號(hào):170615975),2周內(nèi)依病情需加至治療劑量(2~5 mg/d)。在住院治療過程中記錄患者月經(jīng)情況,可以使用勞拉西泮片(山東信宜制藥有限公司,批號(hào):171001)0.5~1.0 mg/d,普萘洛爾片(江蘇亞邦愛普森制藥有限公司,批號(hào):1801011)20~30 mg/d對(duì)睡眠障礙及心動(dòng)過速分別進(jìn)行處理,也可以酌情使用苯海索片及護(hù)肝藥等對(duì)癥支持治療。

      1.3 觀察指標(biāo)及檢測(cè)方法

      治療前及治療后第6周末上午7∶00分別空腹采靜脈血,檢測(cè)PRL及MPRL水平,血常規(guī)、血糖,肝、腎、甲狀腺功能。檢測(cè)PRL所用儀器為美國(guó)貝克曼庫(kù)爾特有限公司生產(chǎn)的ACCESS型全自動(dòng)微粒子化學(xué)發(fā)光免疫分析系統(tǒng),所用PRL試劑盒為該公司配套的試劑盒(生產(chǎn)批號(hào):07218UI00);用酶聯(lián)免疫吸附測(cè)定的方法檢測(cè)MPRL,MPRL試劑盒為人MPRL檢測(cè)Elisa試劑盒(生產(chǎn)批號(hào):E20180301A)。檢驗(yàn)過程嚴(yán)格按試劑盒說明書進(jìn)行操作。

      1.4 分組標(biāo)準(zhǔn)

      根據(jù)PRL及MPRL含量將65例患者分為四個(gè)亞組:①PRL正常組:患者血清PRL含量≤29.2 ng/mL;②高PRL血癥組:患者血清PRL含量>29.2 ng/mL[1];③MPRL血癥組:患者血清PRL達(dá)到高PRL血癥水平且MPRL水平/總PRL水平≥30%[1];④非MPRL血癥組:患者血清PRL水平達(dá)到高PRL血癥但未達(dá)到MPRL血癥水平。

      1.5 統(tǒng)計(jì)學(xué)方法

      采用SPSS 23.0對(duì)所得數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析,計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,組間比較采用t檢驗(yàn),計(jì)數(shù)資料采用例數(shù)和百分率表示,組間比較采用χ2檢驗(yàn)。以P < 0.05為差異有統(tǒng)計(jì)學(xué)意義。

      2 結(jié)果

      2.1 四個(gè)亞組一般資料比較

      四個(gè)亞組一般資料比較,差異無統(tǒng)計(jì)學(xué)意義(P > 0.05)。見表1。

      2.2 治療前后PRL及MPRL含量比較

      65例患者治療后PRL及MPRL水平較治療前明顯升高,差異均有高度統(tǒng)計(jì)學(xué)意義(均P < 0.01)。見表2。

      2.3 四個(gè)亞組發(fā)生月經(jīng)延遲情況比較

      四個(gè)亞組月經(jīng)延遲發(fā)生率比較,差異有統(tǒng)計(jì)學(xué)意義(P < 0.05);MPRL血癥組月經(jīng)延遲發(fā)生率與PRL正常組比較,差異無統(tǒng)計(jì)學(xué)意義(χ2=0.757;P = 0.384);非MPRL血癥組月經(jīng)延遲發(fā)生率分別高于高PRL血癥組、MPRL血癥組及PRL正常組,差異有統(tǒng)計(jì)學(xué)意義(χ2=6.875,P = 0.009;χ2=21.670,P = 0.000;χ2=25.321,P = 0.000);高PRL血癥組月經(jīng)延遲發(fā)生率高于MPRL血癥組及PRL正常組,差異有統(tǒng)計(jì)學(xué)意義(χ2=8.231,P = 0.004;χ2=11.457,P = 0.001)。見表3。

      3 討論

      PRL主要有:?jiǎn)误w小分子泌乳素(SPRL)、大分子泌乳素(BPRL)以及MPRL分子三種[10]。1985年Jackson等人首次將以MPRL水平升高為主的高PRL血癥患者稱為MPRL血癥[11],此類患者血液中PRL以MPRL為主,SPRL和BPRL水平正常且無明顯臨床癥狀[12]。在精神醫(yī)學(xué)領(lǐng)域國(guó)內(nèi)外對(duì)PRL研究甚廣[1-3],而對(duì)PRL中的MPRL相關(guān)研究較少[13-14],這也是進(jìn)行本研究的主要原因。

      抗精神病藥物可以導(dǎo)致患者出現(xiàn)高PRL血癥從而出現(xiàn)泌乳或者月經(jīng)延遲甚至閉經(jīng),影響患者服藥的依從性[4-5]。在臨床即使出現(xiàn)高PRL血癥,也有一部分患者不會(huì)出現(xiàn)月經(jīng)延遲或者閉經(jīng)。究其原因,除個(gè)體差異外,臨床現(xiàn)有的常規(guī)檢測(cè)方法所檢測(cè)的PRL實(shí)際上是總泌乳素(T-PRL)而沒有區(qū)分出其中的MPRL[10]。本研究對(duì)患者PRL及MPRL進(jìn)行檢測(cè),發(fā)現(xiàn)經(jīng)過抗精神病藥物治療后患者的PRL及MPRL水平明顯增高,部分患者達(dá)到高M(jìn)PRL血癥,這表明抗精神病藥物所致高PRL血癥的確有一部分患者是高M(jìn)PRL血癥,與其他研究結(jié)果一致[14-15]。有大量研究顯示MPRL分子無實(shí)際生物學(xué)活性,不會(huì)引起PRL的垂體負(fù)反饋調(diào)節(jié),不會(huì)導(dǎo)致臨床癥狀(閉經(jīng)或者泌乳)[7],但其半衰期較長(zhǎng)且易在血流中積聚,導(dǎo)致MPRL血癥[15-16]。這就不難解釋在本研究中高PRL血癥患者只有部分患者出現(xiàn)月經(jīng)延遲。

      本研究顯示,MPRL血癥患者與無高PRL血癥患者出現(xiàn)月經(jīng)延遲的情況均很低,明顯低于無MPRL升高的高PRL血癥患者,進(jìn)一步表明MPRL的確無生物活性,可能不會(huì)導(dǎo)致患者月經(jīng)延遲,與其他研究結(jié)果一致[10-12]。這也提示在臨床患者出現(xiàn)高PRL血癥時(shí)應(yīng)該進(jìn)行MPRL的檢測(cè)[14],以便確認(rèn)是否需要對(duì)高PRL進(jìn)行干預(yù),預(yù)判高PRL血癥是否會(huì)導(dǎo)致患者月經(jīng)延遲甚至閉經(jīng),對(duì)患者進(jìn)行及時(shí)準(zhǔn)確的宣教,提高患者對(duì)治療的依從性[4-5]。

      臨床對(duì)抗精神病藥物所致高PRL血癥,往往采用減藥[13]、聯(lián)合阿立哌唑[17-18]或者中醫(yī)中藥[19]等辦法來處理,這些方法有的可能導(dǎo)致患者病情波動(dòng)甚至復(fù)發(fā),有的可能增加患者服藥負(fù)擔(dān),降低患者對(duì)治療的依從性。美國(guó)內(nèi)分泌學(xué)會(huì)臨床診療指南強(qiáng)調(diào)對(duì)于無相關(guān)臨床癥狀的高PRL血癥患者,應(yīng)進(jìn)一步測(cè)定MPRL水平和考慮MPRL血癥的可能[20]。本研究顯示高PRL血癥患者有42.9%(21/49)達(dá)到MPRL血癥,顯然對(duì)于高PRL血癥的治療需要慎重對(duì)待,避免對(duì)這一部分患者造成不必要的影響。這也提示臨床對(duì)高PRL血癥患者進(jìn)行必要的MPRL檢測(cè)有利于避免誤診、誤治[10]。

      本研究提示利培酮所致MPRL血癥可能不會(huì)導(dǎo)致患者月經(jīng)延遲,臨床上檢測(cè)MPRL有利于指導(dǎo)高PRL血癥的治療。當(dāng)然,本研究作為描述性研究,未設(shè)立對(duì)照、觀察時(shí)間短等具有一定的局限性,下一步將克服本研究中的不足進(jìn)行進(jìn)一步探討。

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      (收稿日期:2020-01-22)

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