腹腔镜手术对HIV感染者免疫功能的影响
【摘要】 目的:检测HIV(+)者腹腔镜手术前后主要细胞和体液免疫指标的变化并与HIV(?)者对照,探讨微创手术对HIV感染者主要免疫功能的影响。方法:将42例胆囊疾病患者分为2组:观察组(HIV+)22例,对照组(HIV?)20例。用同样方法施行腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)。于术前1d,术后3、7d(POD3,7)检测血常规、白蛋白,CD3、CD4、CD8及其百分比和CD4/CD8;IgG、IgM、IgA,补体C3和C4,CRP。HIV(+)者检测HIV?RNA。常规统计学方法处理所得数据。结果:白细胞总数HIV(?)组>HIV(+)组(POD3,7)(P<0.05)。淋巴和中性粒细胞无显著变化(P>0.05)。白蛋白2组手术前后>35 g/L。IgA手术前后HIV(+)>HIV(?)(P<0.05)。IgG、IgGM、C3和C4 2组手术前后均无显著变化,均在正常范围。CD4 HIV(+)者术前1天至术后1月<50 copy/ml。组间比较:CD4手术前后HIV(+)< HIV(?)(P<0.05)。HIV(+)组内CD4(POD 3) 【关键词】 HIV感染 腹腔镜术 免疫功能 Effects of laparoscopic surgery on immune function of HIV?infected patients 【Abstract】 Objective:To evaluate the effects of laparoscopic operations on immune function of HIV?infected patients.Methods:Fourty?two cases of benign gallbladder diseases were divided into two groups:22 HIV(+)cases and 20 HIV(?)cases,and all cases underwent the laparoscopic cholecystectomy(LC).All cases were analyzed for peripheral blood cells and plasma albumin,the subset of T Lymphocyte(CD3,CD4,CD8,their percentages and CD4/CD8)with flow cytometric assessment,IgG,IgM,IgA,C3,C4 and CRP on the day before operation,the third and seventh day after operation.Plasma HIV?RNA was detected in HIV positive cases.Statistical analysis was performed by SPASS 12.0.Results:There were no clinically significant decrease of peripheral blood cells and plasma albumin in HIV(+)group compared with HIV(?)and HIV?RNA measured below 50 copies/ml in all of HIV(+)group.Mean CD4counts in HIV(+)patients were 309.1,260.5,300 cell/ml while 499.3,580,462 in HIV(?)group respectively on POD 1,3,7.There were statistical significant difference between the two groups(P<0.05).In HIV(+)group,CD4 were significantly lower on POD 3 than those on POD 1 and 7(P<0.05).There were also lower expression CD4/CD8 in HIV(+)group(0.47,0.53,0.50)than those in HIV(?)group(0.96,1.04,1.15)(P<0.05).No significant difference of CD4 were seen in the same group of HIV(?)group and CD4/CD8 in the same group of the two in pre? and postoperative time(P>0.05).IgA in HIV(+)group were higher than those in HIV(?)group and There was no clinically significant difference of IgG、IgM,C3,C4 in preoperative and postoperative time between the two groups.Significantly higher CRP of preoperation was seen in HIV(+)group than those of postoperation.Adversely,CRP of preoperation in HIV(?)group were less than that of postoperation.No postoperative complications and mortality occurred in all cases.Conclusions:LC has no clinical effects on humoral immune responses of HIV?infected patients.Although LC has been shown mild immunesuppression temporarily in HIV(+)patients, LC may result in less induced surgical trauma than conventional open surgery without postoperative risk of complications or death.However,perioperative CD4 and HIV?1 RNA may be useful risk indicators for HIV(+)patients.In these cases,CD4 count should be maximized to ≥200 cell/ml so as to minimize postoperative complications and mortality. 本研究通过检测HIV感染者腹腔镜手术(laparoscopic surgery,LS)前后主要细胞和体液免疫指标的变化,探讨LS对HIV感染者免疫功能的影响。 1 资料与方法 患者分为2组,观察组:经蛋白印迹法确诊为HIV感染者22例中男15例,女7例,32~52岁,平均39.3岁,无艾滋病相关症状,经B超诊断为慢性胆囊炎、胆囊结石13例;急性胆囊炎、胆囊结石7例,胆囊息肉2例;对照组:经ELISA法初筛HIV(?)20例中男6例,女14例,42~56岁,平均50.2岁;其中慢性胆囊炎急性发作并胆囊结石12例,急性胆囊炎、胆囊结石6例,胆囊息肉2例,无其他慢性消耗性疾病。2组用同法完成腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)。手术顺利,无麻醉和手术意外。2组分别于术前1d,术后3、7d(POD?1,3,7)抽外周血,用常规方法检测血常规、白蛋白、IgG、IgM、IgA,补体C3和C4,CRP。用流式细胞仪检测血中CD3、CD4、CD8,各淋巴细胞百分比和CD4/CD8。HIV(+)用bDNA法检测HIV?RNA。主要数据的统计学处理按常规进行。 2 结 果 2组均于术前1d、术后3、7d(POD?1,3,7)抽外周血检测。外周血白细胞数和主要分类结果见表1。2组手术前后白蛋白>35g/L。观察组患者术前1天至术后1月的HIV?RNA<50 copy/ml。2组主要淋巴细胞亚群检测结果的平均值见表2。2组同组和组间比较,手术前后CD3和CD8及其百分比无显著变化(P>0.05)。表1 2组患者手术前后外周血白细胞数与炎性指标的结果(略)表2 2组患者手术前后主要淋巴细胞亚群的变化(略) 3 讨 论 外科手术对机体免疫功能的影响有多方面因素。高龄、伴随疾病以及同时出现的药物,手术后的创面愈合也会不同程度的影响患者的免疫功能[1] 。除了抗菌药物外,减少手术后并发症,尤其术后感染的最有效方法是减少手术创伤,进而减轻创伤带来的应激反应对机体免疫功能的抑制。营养支持和保持机体内环境的平衡稳定也可改善机体免疫功能。腹腔镜手术与传统开放手术比较,术后患者疼痛较轻,创伤小,应激反应小,康复快,相应对机体免疫功能的抑制较小[2]。然而,术中CO2气腹对机体组织结构、代谢和免疫功能的影响,尤其对特异性细胞免疫功能的影响至今仍不完全明了[3,4]。
【Key words】 HIV infection;Laparoscopy;Immune function
外科手术对艾滋病患者和HIV感染者的影响越来越受到关注。不同类型的手术创伤使艾滋病患者和HIV感染者的免疫功能在一定程度上发生了改变,影响到术后并发症的发生率和手术死亡率,从而直接或间接关系到手术的安全性。有学者根据外周血CD4值将HIV感染者的免疫状态分为3级[5]:无免疫抑制(non immunodepressed,NID),CD4>500个/μl;轻度免疫抑制(mildly immunodepressed,MID),CD4200~500;重度免疫抑制(severely immunodepressed,SID),CD4<200。CD4、病毒载量和全身营养状况(尤其白蛋白等)是常用于评估HIV感染者是否发病、疾病预后及是否有效的指标[6]。
本研究显示,LC后HIV感染者白细胞数、中性粒细胞等变化不显著,且2组CRP的不同变化都表明,HIV感染者微创术后应激和炎症反应比对照组要低,其临床意义尚待进一步研究。本研究中,HIV感染者无抗病毒治疗情况下特异性细胞免疫状态都为MID,尤其术前CD4和CD4/CD8都明显低于正常对照,表明患者尽管尚未发病,且病毒载量也在正常范围,但细胞免疫功能已受到影响。CD4在控制机体有害的炎症反应,维持免疫平衡,减轻创伤后的免疫抑制等方面起着重要的作用[7]。CD8在这些方面究竟起何种作用仍未明了[8]。本研究最能反映艾滋病患者或HIV感染者细胞免疫功能或与手术耐受性相关的CD4值在术后短时间内轻度下降,1周恢复到术前水平。这种现象是否由于LC的微创对细胞免疫有短暂的抑制作用,抑或同时存在术中高压CO2气腹对机体免疫的影响,有待进一步研究。LC对HIV感染者的主要体液免疫指标无显著影响,也表明了细胞免疫在HIV感染中的重要性。本研究中,HIV感染者术后均未出现手术并发症(各种形式的感染等)、艾滋病相关症状,也没有死亡病例,应该与术前CD4值和CD4/CD8相对较高,特异性细胞免疫功能仍有相当“储备”等因素有关。有学者认为,术后并发症主要与机体免疫状态有关,而与抗病毒治疗和围手术期抗生素预防无直接关系[9]。严重并发症甚至死亡病例多发生在SID患者以及HAART仍不能有效控制病情的艾滋病患者[10]。就HIV感染者或艾滋病患者而言,选择合适的病例和手术指征,术前适当和有针对性的准备,能够达到减少手术并发症和风险,改善生活质量的目的[11]。
总之,LS对HIV感染者的特异细胞免疫功能有短暂的轻度抑制作用。尽管如此,LS对于多数HIV感染者而言是安全的,预后也较好。但术前应常规检测CD4和病毒载量,将CD4作为评估手术风险的主要指标,病毒载量作为辅助判断标准。术前CD4≥200是保证手术安全的基本条件。CD4较低或病毒载量高时,可考虑术前应用HAART治疗提升CD4值和降低病毒载量以确保手术的安全。
【】
[1]Esposito S.Immune system and surgical site infection[J].J Chemother,2001,13(1):12?16.
[2]Novitsky YW,Litwin DE,Callery MP.The net immunologic advantage of laparoscopic surgery[J].Surg Endosc,2004,18(10):1411?1419.
[3]Neuhaus SJ,Watson DI.Pneumoperitoneum and peritoneal surface changes:a review[J].Surg Endosc,2004,18(9):1316?1322.
[4]Ng CS,Whelan RL,Lacy AM,et al.Is minimal access surgery for cancer associated with immunologic benefits?[J].World J Surg,2005,29(8):975?981.
[5]Bahebeck J,Bedimo R,Eyenga V,et al.The management of musculoskeletal infection in HIV carriers[J].Acta Orthop Belg,2004,70(4):355?360.
[6]Lin PH,Bush RL,Yao Q,et al.Abdominal aortic surgery in patients with human immunodeficiency virus infection[J].Am J Surg,2004,188(6):690?697.
[7]Choileain NN,MacConmara M,Zang Y,et al.Enhanced regulatory T cell activity is an element of the host response to injury[J].J Immunology,2006,176(1):225?236.
[8]Tomaras GD,Lacey SF,McDanal CB,et al.CD8+ T cell?mediated suppressive activity inhibits HIV?1 after virus entry with kinetics indicating effects on virus gene expression[J].Proc Natl Acad Sci USA,2000,97(7):3503?3508.
[9]Grubert TA,Reindell D,Kastner R,et al.Rates of postoperative complications among human immunodeficiency virus?infected women who have undergone obstetric and gynecologic surgical procedures[J].Clin Infect Dis,2002,34(6):822?830.
[10]Miro JM,DelRio A,Mestres CA.Infective endocarditis and cardiac surgery in intravenous drug abusers and HIV?1 infected patients[J].Cardiol Clin,2003,21(2):167?184.
[11]Wheeler DW,Baigrie RJ.Palliative surgery for acute bowel obstruction caused by Kaposi's sarcoma in a patient with AIDS[J].Int J Clin Pract,2003,57(4):347?348.