張阿芳

（駐馬店市中醫(yī)院骨傷科，河南 駐馬店 463000）

帕瑞昔布鈉超前鎮(zhèn)痛對(duì)髖關(guān)節(jié)置換術(shù)患者IL-6和TNF-α的影響

張阿芳

（駐馬店市中醫(yī)院骨傷科，河南 駐馬店 463000）

目的 探討帕瑞昔布鈉超前鎮(zhèn)痛對(duì)髖關(guān)節(jié)置換術(shù)后患者炎癥細(xì)胞因子的影響，并進(jìn)一步觀察術(shù)后鎮(zhèn)痛效果。方法 本組患者60例，年齡40～65歲，ASAⅠ-Ⅱ級(jí)，擇期在全麻下行髖關(guān)節(jié)置換術(shù)。隨機(jī)分成觀察組和對(duì)照組，每組30例。麻醉前20 min觀察組靜脈注射帕瑞昔布鈉40 mg（用生理鹽水稀釋成4 mL）,對(duì)照組靜脈注射生理鹽水4 mL。分別于靜推帕瑞昔布鈉或生理鹽水前10 min（T1）、術(shù)畢（T2）、術(shù)后6 h（T3）、術(shù)后12 h（T4）、術(shù)后24 h（T5）采上肢靜脈血樣，測定IL-6、TNF-α的血漿濃度。采用視覺模擬評(píng)分法（VAS）評(píng)價(jià)術(shù)畢即刻、術(shù)后2 h、6 h、12 h、24 h鎮(zhèn)痛效果。結(jié)果 患者血漿IL-6濃度于T3、T4、T5時(shí)點(diǎn)較術(shù)前顯著升高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；觀察組血漿IL-6濃度于T3、T4、T5時(shí)點(diǎn)比對(duì)照組顯著降低，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）?；颊哐獫{TNF-α濃度于T4、T5時(shí)點(diǎn)較術(shù)前顯著升高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；觀察組血漿TNF-α濃度在T4、T5時(shí)間點(diǎn)比對(duì)照組顯著降低，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。觀察組患者在術(shù)畢即刻、術(shù)后2 h、6 h、12 h VAS評(píng)分均顯著低于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。 結(jié)論 帕瑞昔布鈉超前鎮(zhèn)痛可有效緩解全髖關(guān)節(jié)置換術(shù)患者術(shù)后疼痛，抑制炎性介質(zhì)釋放，降低神經(jīng)系統(tǒng)敏感性，利于患者術(shù)后康復(fù)。

帕瑞昔布鈉；超前鎮(zhèn)痛；髖關(guān)節(jié)置換術(shù)；IL-6；TNF-α

髖關(guān)節(jié)置換術(shù)（total hip replacement ，THR）是以人造髖關(guān)節(jié)置換所有或部分髖關(guān)節(jié)，重建關(guān)節(jié)運(yùn)動(dòng)功能的一種修復(fù)性手術(shù)，是治療多種終末期髖關(guān)節(jié)疾病最有效最普遍的方法[1]。THR能夠矯正髖關(guān)節(jié)畸形，恢復(fù)髖關(guān)節(jié)功能，但髖關(guān)節(jié)置換手術(shù)所致創(chuàng)傷較大，而手術(shù)創(chuàng)傷可引起術(shù)后疼痛,并產(chǎn)生一系列炎癥反應(yīng)。Dahl等[2]認(rèn)為,超前鎮(zhèn)痛是指在傷害性刺激作用機(jī)體前采取措施，防止中樞和外周神經(jīng)敏感化，消除或減輕傷害性刺激所致疼痛。環(huán)氧化酶（COX）抑制劑可通過降低外周COX與前列腺素（PGs）合成酶的活性，抑制外周敏感化，從而達(dá)到超前鎮(zhèn)痛的目的。帕瑞昔布鈉是一種新型非甾體解熱鎮(zhèn)痛藥（NSAIDs），具有抗炎、鎮(zhèn)痛、解熱的作用。本研究旨在探討帕瑞昔布鈉超前鎮(zhèn)痛對(duì)THR患者術(shù)后炎性細(xì)胞因子IL-6、TNF-α的影響和術(shù)后鎮(zhèn)痛效果。

1 資料與方法

1.1 一般資料

選取2013年9月至2014年4月在駐馬店市中醫(yī)院擇期行髖關(guān)節(jié)置換術(shù)患者60例為研究對(duì)象，性別不限，年齡43～68歲，體質(zhì)量51～75 kg，ASA Ⅰ-Ⅱ級(jí)，無免疫系統(tǒng)疾病，心、肝、肺、腎功能未見異常，術(shù)前4周未接受過阿片類藥物或非甾體類藥物治療, 無感染癥狀，無藥物過敏史及慢性疼痛史，無長期服用麻醉性鎮(zhèn)痛藥物史。將該60例患者隨機(jī)分為觀察組與對(duì)照組，每組30例。兩組患者性別、年齡、體質(zhì)量、身高、手術(shù)時(shí)間、術(shù)中失血量等一般情況比較差異無統(tǒng)計(jì)學(xué)意義（P＞0.05），見表1。

表1 兩組患者一般資料及術(shù)中情況比較（x±s，n=30）

1.2 麻醉和實(shí)驗(yàn)方法

患者進(jìn)入手術(shù)室，常規(guī)監(jiān)測生命體征。麻醉前20 min觀察組靜脈注射帕瑞昔布鈉40 mg（用生理鹽水稀釋成4 mL）,對(duì)照組靜脈注射生理鹽水4 mL。誘導(dǎo)麻醉：采用咪達(dá)唑侖0.05 mg/kg、芬太尼2 μg/kg、異丙酚 1.5～2.0 mg/kg或依托咪酯0.2 mg/kg 、維庫溴銨 0.08 mg/kg對(duì)兩組患者進(jìn)行麻醉誘導(dǎo)，為患者行氣管插管，氣管插管成功后行機(jī)械輔助呼吸，潮氣量8～10 mL/kg，隨時(shí)調(diào)節(jié)呼吸參數(shù)，維持呼氣末二氧化碳濃度（PETCO2）在35～35 mmHg。常規(guī)復(fù)蘇后拔氣管插管。

1.3 觀察指標(biāo)及檢測方法

全部患者分別于靜推帕瑞昔布鈉或生理鹽水前10 min（T1）、術(shù)畢即刻（T2）、6 h（T3）、12 h（T4）、24 h（T5）各時(shí)間點(diǎn)抽取上肢靜脈血樣。采用酶聯(lián)免疫吸附試驗(yàn)雙抗體夾心法測定不同時(shí)間點(diǎn)IL-6、TNF-α血漿濃度。觀察兩組患者術(shù)畢即刻、術(shù)后2 h、6 h、12 h、24 h靜態(tài)和動(dòng)態(tài)視覺模擬評(píng)分（VAS），評(píng)價(jià)患者疼痛程度（0分為無痛，10分為劇痛），通常認(rèn)為VAS≤3分為鎮(zhèn)痛效果好。

1.4 統(tǒng)計(jì)學(xué)處理

采用SPSS11.0軟件包進(jìn)行數(shù)據(jù)分析，計(jì)量資料以（x±s）表示；組內(nèi)比較采用重復(fù)測量資料方差分析；觀察組和對(duì)照組比較采用t檢驗(yàn)（方差齊時(shí)）或t'檢驗(yàn)（方差不齊時(shí)）；計(jì)數(shù)資料比較采用卡方檢驗(yàn)。 P＜0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié) 果

2.1 兩組患者炎性細(xì)胞因子IL-6、TNF-α血漿濃度比較

患者IL-6血漿濃度于T3、T4、T5時(shí)間點(diǎn)均較術(shù)前顯著升高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；兩組患者比較，觀察組血漿IL-6濃度在T3、T4、T5時(shí)間點(diǎn)比對(duì)照組顯著降低，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。患者血漿TNF-α濃度于T4、T5時(shí)間點(diǎn)較術(shù)前顯著升高，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；觀察組TNF-α濃度在T4、T5時(shí)間點(diǎn)比對(duì)照組顯著降低，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。見表2。

表2 兩組患者 IL-6、TNF-α的平均血漿濃度（x±s，n=30）

2.2 兩組患者VAS評(píng)分比較

兩組患者比較，觀察組患者在術(shù)畢、術(shù)后2 h、6 h、12 h VAS評(píng)分均顯著低于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。術(shù)后24 h VAS評(píng)分觀察組和對(duì)照組差異無統(tǒng)計(jì)學(xué)意義（P＞0.05 ），見表3。

表3 兩組患者視覺模擬評(píng)分比較（x±s， n=30）

3 討 論

THR是沿患側(cè)髖關(guān)節(jié)作一切口，首先暴露髖關(guān)節(jié)，其次切除股骨頭及髖關(guān)節(jié)窩，最后將人工關(guān)節(jié)頭和金屬桿置入股骨，再將塑料關(guān)節(jié)窩置入已擴(kuò)大的骨盆關(guān)節(jié)凹內(nèi)。由于該手術(shù)創(chuàng)面較大，可導(dǎo)致患者術(shù)中、術(shù)后產(chǎn)生中度至重度疼痛。THR可對(duì)患者產(chǎn)生傷害刺激及炎癥反應(yīng)，導(dǎo)致炎性介質(zhì)、致痛物質(zhì)等大量釋放，除造成直接疼痛外，還可引發(fā)組織水腫、血管擴(kuò)張，降低疼痛閾值，并導(dǎo)致周圍痛覺過敏[3]。

生理狀態(tài)下，抗炎細(xì)胞因子（IL-4、IL-10、IL-11、IL-13、IL-β）和促炎細(xì)胞因子（TNF-α、IL-l、IL-6、IL-8）兩種因子處于脆弱平衡，該平衡容易被手術(shù)創(chuàng)傷等異常情況打破。促炎細(xì)胞因子與傷害刺激間存在反饋級(jí)聯(lián)效應(yīng)，而疼痛體驗(yàn)也可使促炎細(xì)胞因子水平升高。目前研究顯示，TNF-α和IL-6是在手術(shù)或創(chuàng)傷早期表達(dá)最早最敏感的組織損傷標(biāo)志，他們的升高水平與組織損傷程度密切相關(guān)[4]。IL-6是代表機(jī)體組織損傷程度和炎性反應(yīng)的重要指標(biāo)。IL-6 作為細(xì)胞因子中與疾病轉(zhuǎn)歸及愈后關(guān)系密切的炎癥介質(zhì)之一，處于樞紐位置，手術(shù)創(chuàng)傷早期機(jī)體可生成大量 IL-6，且血清IL-6水平可反映應(yīng)激反應(yīng)的強(qiáng)烈程度[5]。本研究顯示，患者血漿 IL-6 在術(shù)畢不同時(shí)點(diǎn)均較術(shù)前顯著升高，表明手術(shù)創(chuàng)傷刺激令機(jī)體產(chǎn)生急性炎癥反應(yīng)，使血漿中 IL-6 急劇升高。觀察組術(shù)后6 h、12 h、24h血漿 IL-6濃度均顯著低于對(duì)照組，是由于兩組患者組織損傷范圍、程度及麻醉方式相似，所以認(rèn)為，血漿 IL-6 濃度變化可能由帕瑞昔布鈉通過抑制PGs合成，減少炎癥因子生成所導(dǎo)致。 TNF-α 是機(jī)體接觸傷害性刺激后所分泌的炎性細(xì)胞因子，能增強(qiáng)巨噬細(xì)胞吞噬功能，主要生物活性是致使腫瘤細(xì)胞壞死，且具有抗感染及免疫調(diào)節(jié)作用。TNF-α常作為表達(dá)炎性細(xì)胞因子分泌情況的標(biāo)志物。本研究結(jié)果顯示，患者血漿 TNF-α 濃度于術(shù)后12 h、24 h較術(shù)前顯著升高。觀察組血漿 TNF-α 濃度于術(shù)后12 h、24 h顯著低于對(duì)照組。此結(jié)果顯示，帕瑞昔布鈉能抑制術(shù)后 TNF-α 的釋放，說明帕瑞昔布鈉在平衡炎癥細(xì)胞因子方面有較好作用。

帕瑞昔布鈉是伐地昔布酰胺的前體化合物，靜注后迅速被肝臟羧酸酯酶水解成伐地昔布[6]，伐地昔布在治療濃度時(shí)能選擇性抑制環(huán)氧化酶-2（COX-2），能抑制PGs合成，發(fā)揮鎮(zhèn)痛抗炎作用。本組THR術(shù)后患者VAS評(píng)分顯示，觀察組患者術(shù)畢即刻、術(shù)后2 h、6 h、12 h VAS評(píng)分均顯著低于對(duì)照組。說明本實(shí)驗(yàn)中帕瑞昔布鈉在一定程度上增強(qiáng)了THR術(shù)后鎮(zhèn)痛效果，但隨術(shù)后時(shí)間延長，藥效逐漸減弱，其鎮(zhèn)痛作用也在逐漸減弱。這可能與伐地昔布的作用時(shí)間有關(guān)。

綜上所述，預(yù)先應(yīng)用帕瑞昔布鈉超前鎮(zhèn)痛，可減少THR患者炎性細(xì)胞因子IL-6、TNF-α釋放，有效提高術(shù)后鎮(zhèn)痛質(zhì)量，對(duì)THR患者術(shù)后康復(fù)有重要意義。

[1] 李雪萍, 劉江洪, 劉才堂, 等. 帕瑞昔布提高術(shù)后靜脈鎮(zhèn)痛的安全性和有效性[J]. 臨床醫(yī)學(xué), 2011, 31(8): 15-18.

[2] DAHL J B, MINIEHE S. Pre-emptive analgesia[J]. Br Med Bull, 2004, 2l(1): 13-27.

[3] 吳進(jìn), 戴甫成, 袁菊芳, 等. 切口浸潤麻醉復(fù)合帕瑞昔布靜注用于腹腔鏡膽囊切除術(shù)后鎮(zhèn)痛[J]. 臨床麻醉學(xué)雜志, 2011, 27(4): 351-352.

[4] RITTNER H L, LUX C, LABUZ D, et a1. Neurokinin-l rceptor antagonists inhibit the recnIitment of opioid-containing leukocytes and impair peripheral antinoeiception [J]. Anesthesiology, 2007, 107(6): 1009-1017.

[5] MOSELLI N M, BARICOCCHI E, RIBERO D, et al. Intra-operative epidural analgesis prevents the early proinflammatory response to surgical trauma, Results form a prospective randomized clinical trial of intraoperative epidural versus general analgesia[J]. Ann Surg Oncol, 2011, 18(10): 272.

[6] FOMAJ M, COLUCCI R, GRAZIANI F, et a1. Cyclooxygense-2 induction after oral surgery does not entirely account for analgesia after selective blockade of cyclooxygenase-2 in the preoperative period [J]. Anesthesiogy, 2006, 104(1): 152-157.

（責(zé)任編輯：劉俊華）

Effects of IL-6, TNF-α of preemptive analgesia with parecoxib sodium on the patients with total hip replacement

ZHANG Afang
( Zhumadian City Hospital of Traditional Chinese Medicine, Zhumadian 463000, China )

Objective To investigate the affected inflammatory cytokines of preemptive analgesia with parecoxib sodium on the patients with hip replacement, and observe the postoperative analgesia. Methods 60 cases aged 40 to 65 years, ASA Ⅰ - Ⅱ grade, under general anesthesia for elective hip arthroplasty were randomly divided into observation group and control group, 30 cases in each group. Before general anesthesia for 20 min, the patients of observation group were injected parecoxib sodium 40 mg (diluted with saline to 4 mL) intravenously, the patients of control group were given saline 4 mL intravenously. Before bolus parecoxib sodium or saline 10 min (T1), end of the surgery (T2), after 6 h (T3), Postoperative 12 h (T4), Postoperative 24 h (T5) Exsanguinate vein blood samples and detecting the inflammatory cytokine interleukin -6 (IL-6), tumor necrosis factor-α (TNF-α) inthe plasma concentrations respectively. Using a visual analogue scale (VAS) evaluation of surgery immediately, after operation for 2 h, 6 h, 12 h, 24 h analgesic effects were observed . Results Inflammatory cytokines: The IL-6 plasma concentration of the two groups were significantly higher at the time point T3,T4 and T5 than preoperation. There was statistical difference between the 2 groups(P＜0.05). The IL-6 plasma concentration of the experimental group at the time point T3,T4 and T5 was obviously lower than that of the control group(P＜0.05). The TNF-α plasma concentration of the two groups were significantly higher at the time point T4 and T5 than pre-operation (P＜0.05). The TNF-α plasma concentration of the experimental group at the time point T4 and T5 were obviously lower than that of the control group and there was statistical difference(P＜0.05). Stress hormone concentration: The plasma concentration of the two groups at the different time point were clearly higher than that before operation and there was statistical difference(P＜0.05). The plasma concentration of the experimental group at the different time points T2,T3, T4 and T5 were obviously lower than that of the control group. The plasma E concentration of the two groups at the time point T2 were obviously higher than that before operation. The plasma E concentration of the experimental group at the time point T2 were obviously lower than that of the control group and there was statistical difference(P＜0.05). The evaluation result of VAS: The VAS evaluation results of the experimental group at the different time points ---the very end of the operation, 2h, 6h,12h after the operation, were significantly lower than that of the control group and there was a significant difference between the 2 groups (P＜0.05). Conclusion Parecoxib sodium preemptive analgesia can relieve postoperative pain in total hip arthroplasty patients, inhibit the release of inflammatory mediators, reduce the sensitivity of the nervous system, which will help the rehabilitation of patients after surgery.

parecoxib sodium; preemptive analgesia; total hip replacement; IL-6; TNF-α

R614

A

1674-490X(2014)03-0043-04

2014-04-20

張阿芳（1983—），女，河南上蔡人，主治醫(yī)師，主要從事骨科臨床研究。E-mail: 1565906379@qq.com