俞逊婕+++++翁明钢++++梁赣锋+++沈扬+++蒋亚萍
[摘要] 意图 评论肠道去污剂对肝硬化患者肝功用、血浆内毒素、肿瘤坏死因子-α(TNF-α)及降钙素原(PCT)水平的影响。 办法 将84例肝硬化患者随机分为对照组和调查组。两组均予以低盐饮食、弥补白蛋白及保肝利尿等对症医治。调查组加用口服肠道去污剂10 mL/次,3次/d,连用14 d。调查并比较两组医治前和医治14 d后肝功用、血浆内毒素、TNF-α及PCT水平的改动。成果 医治14 d后,两组ALT、AST和TBIL均显着下降(P<0.05或P<0.01),且调查组下降更显着(P<0.05);一起两组血浆内毒素、TNF-α及PCT水均匀显着下降(P<0.05或P<0.01),且调查组下降更显着(P<0.05)。定论 选用肠道去污剂医治肝硬化能显着改进肝功用目标,并能下降血浆内毒素、TNF-α及PCT水平,然后减轻肠源性内毒素血症,维护及改进患者的肠道屏障功用。
[关键词] 肝硬化;肠道去污剂;肝功用;肿瘤坏死因子-α;降钙素原
[中图分类号] R575.2[文献标识码] A[文章编号] 1673-9701(2014)15-0004-03
Influence of intestinal decontamination agent on liver function, plasma endotoxin, tumor necrosis factor-α (TNF-α) and procalcitonin (PCT) of patients with cirrhosis
YU Xunjie1 WENG Minggang1 LIANG Ganfeng1 SHEN Yang1 JIANG Yaping2
1.Department of Infectious Disease,the First Peoples Hospital of Taizhou in Zhejiang Province(Affiliated Huangyan Hospital of Wenzhou Medical College),Taizhou318020,China; 2.Clinical Laboratory,the First Peoples Hospital of Taizhou in Zhejiang Province (Affiliated Huangyan Hospital of Wenzhou Medical College),Taizhou318020,China
[Abstract] Objective To discuss influence of intestinal decontamination agent on liver function, plasma endotoxin, tumor necrosis factor-α(TNF-α) and procalcitonin(PCT) of patients with cirrhosis. Methods A total of 84 cases of patients with cirrhosis were divided into control group and observation group at random. The patients in two groups were given symptomatic treatment such like low salt diet (LSD), albumin added, liver protection, diuresis and etc. The patients in observation group were additionally given 10 mL intestinal decontamination agent through the mouth per time, three times a day for 14 days. Excepted for oral intestinal decontamination agent, the medical treatment was the same as that in observation group. The changes of liver function, plasma endotoxin, TNF-α and PCT levels of patients in two groups before and 14 days after medical treatment were observed and compared. Results After 14 days medical treatment, ALT, AST and TBIL of patients in two groups obviously declined than before(P<0.05 or P<0.01), and the declining rate of patients in observation group was much higher than that in control group(P<0.05). Meanwhile,the plasma endotoxin, TNF-α and PCT levels of patients in two groups obviously declined than before (P<0.05 or P<0.01), and the declining rate of patients in observation group was much higher than that in control group(P<0.05). Conclusion The application of intestinal decontamination agent to treat patients with cirrhosis can obviously improve the liver function index, reduce the plasma endotoxin, TNF-α and PCT levels, thus, the intestinal endotoxemia (IETM) will be reduced, gut-barrier function of patients will be protected and improved.
[Key words] Cirrhosis; Intestinal decontamination agent; Liver function;Tumor necrosis factor-α(TNF-α); Procalcitonin (PCT)肝硬化是感染科的常见病和多发病,常伴有不同程度的肠源性内毒素血症和肠道屏障功用受损,引起自发性细菌性腹膜炎、肝性脑病和肝肾综合征等并发症,加剧其病况[1,2]。因而,怎么有用减轻肠源性内毒素血症及维护肠屏障功用是医治肝硬化的关键所在[3]。近年来研讨发现肠道去污剂用于医治肝硬化患者具有必定的效果,但机制尚不彻底明晰[4]。本研讨调查了肠道去污剂对肝硬化患者肝功用、血清内毒素、肿瘤坏死因子-α(TNF-α)及降钙素原(PCT)水平的影响,评论其对肝硬化患者肠源性内毒素血症和肠屏障功用的维护效果及效果机制,现报导如下。
1材料与办法
1.1临床材料
挑选2010年1月~2013年9月在我院感染科医治的肝硬化患者84例。归入规范:均契合2000年全国病毒性肝炎会议拟定的有关肝硬化的确诊规范[5],具有典型临床表现,并经生化查看、肝胆超声或CT查看确诊。扫除规范:(1)伴有细菌性腹膜炎、肝性脑病和肝肾综合征等并发症;(2)炎症性肠病、肠瘘、肠梗阻和消化道穿孔等。选用随机数字表将患者随机分为对照组(n=42)和调查组(n=42),两组在性别、年纪和Child-Pugh分级等方面比较差异不显着(P>0.05),具有可比性。见表1。
表1 两组的病例材料比较
1.2 医治办法
两组均予低盐饮食、弥补白蛋白及保肝利尿等对症医治。调查组加用口服肠道去污剂(配方为诺氟沙星0.2 g,乳果糖10 g,黄连素0.3 g和整肠生500 mg)用生理盐水注射液制成悬浊液约30 mL)10 mL/次,3次/d,连用14 d。对照组除不口服肠道去污剂外,余医治与调查组根本相同。调查并比较两组医治前和医治14 d后肝功用、血浆内毒素、TNF-α及PCT水平的改动。
1.3 调查目标
1.3.1 肝功用测定选用全自动生化分析仪测定肝功用目标,包含谷丙转氨酶(ALT)、谷草转氨酶(AST)和血总胆红素(TBIL)等。
1.3.2 血浆内毒素、TNF-α及PCT水平测定选用鲎试验法(试剂盒由厦门市鲎试剂试验厂供给)测定血浆内毒素水平,选用双抗体夹心酶联免疫法(试剂盒由深圳晶美生物公司供给)测定血浆TNF-α水平,选用化学发光法(试剂盒由德国BRAHMS Diagnostica公司供给)测定血浆PCT水平。
1.4 统计学办法
运用SPSS17.0统计学软件,计量材料以均数±规范差(x±s)表明,选用t查验,以P<0.05为差异有统计学含义。
2 成果
2.1 两组医治前后ALT、AST和TBIL水平的比较
两组医治前ALT、AST和TBIL水平比较差异不显着(P>0.05)。医治14 d后,两组ALT、AST和TBIL水均匀有显着下降(对照组医治前后t=2.43、2.45、2.21,P<0.05或调查组医治前后t=3.04、2.91、2.89,P<0.01),且调查组比对照组下降更显着(t=1.19、1.15、1.26,P<0.05)。见表2。
表2 两组医治前后ALT、AST和TB水平的比较(x±s,n=42)
注:与同组医治前比较,*P<0.05,**P<0.01;与对照组比较,▲P<0.05
2.2 两组医治前后血浆内毒素、TNF-α及PCT水平比较
两组医治前血浆内毒素、TNF-α及PCT水平比较差异不显着(P>0.05)。医治14 d后,两组血浆内毒素、TNF-α及PCT水均匀显着下降(对照组医治前后t=2.46、2.36、2.27,P<0.05或调查组医治前后t=3.19、2.91、2.94,P<0.01),且调查组比对照组下降更显着(t=1.21、1.38、1.37,P<0.05)。见表3。
表3 两组医治前后血浆内毒素、TNF-α及PCT水平比较(x±s,n=42)
注:与同组医治前比较,*P<0.05,**P<0.01;与对照组比较,▲P<0.05
3 评论
肝硬化患者门静脉多处于高阻力和高动力这一共同的血液动力学状况,引起肠道和肝脏的微循环改动,肠黏膜毛细血管和静脉过度扩张呈现淤血充血、水肿, 严峻时可引起胃肠黏膜溃烂,使肠道部分免疫力下降,肠道通透性显着上升,加之肝硬化患者肝功用受损,肠道内毒素很多积累,引起血浆内毒素水平反常升高,构成肠源性内毒素血症,加剧患者肠屏障功用障碍[6-8]。内毒素主要是G阴性细菌细胞壁的主要成分。肝硬化患者肠道缺血缺氧时,肠黏膜屏障功用受损,内毒素很多开释经受损肠黏膜进入血循环引起血浆内毒素反常升高,构成肠源性内毒素血症,加剧肝硬化病况[9,10]。TNF-α主要由单核吞噬细胞排泄的炎症因子,可直接或直接发动炎症反响,在肝硬化患者肝细胞炎症反响中起“中心”效果,一起TNF-α可反响肠黏膜结构与功用的完整性,是反映肠黏屏障功用的灵敏目标[11]。PCT是指降钙素前肽物质,无显着的活性,当肝硬化患者呈现肠屏障功用受损时,PCT很多开释入血引起血浆PCT水平升高,血浆PCT水平是反映肠屏障受损和修正[12]。因而,血浆内毒素、TNF-α及PCT水平可反映肝硬化患者肠源性内毒素血症和肠屏障功用的的灵敏目标。经过药物下降血浆内毒素、TNF-α及PCT水平可减轻患者肠源性内毒素血症和维护其肠屏障功用[13,14]。
以平常经过预防性运用灵敏或大剂量抗生素以削减肠道细菌易位,减轻患者肠源性内毒素血症,维护其肠屏障功用,取得了必定的效果。可是长时间大剂量运用抗生素可使肠道细菌,尤其是革兰阴性菌开释内毒素;且长时间大剂量运用抗生素可抑制肠道正常菌群的成长繁衍,使耐药菌很多过成长,引起肠道内毒素水平升高,构成肠源性内毒素血症[15,16]。肠道去污剂经过口服抗生素杀灭肠道内时机致病菌,操控肠源性感染,医治肝硬化取得了较好效果[17,18]。覃慧敏等[19]研讨发现肠道去污剂用于肝硬化患者可改进肝功用目标,下降内毒素水平,减轻肠源性内毒素血症,维护和改进肠屏障功用。王志勇等[20]研讨发现肠道去污剂用于肝硬化医治能显着改进肝细胞目标,康复肝功用,并能下降肠黏膜的通透性及患者内毒素水平,下降细菌性腹膜炎、肝性脑病和肝肾综合征等并发症发生率。本研讨成果发现医治14 d后,调查组患者ALT、AST和TBIL水平比对照组下降更显着,提示肠道去污剂医治肝硬化可改进肝功用目标,有利于肝功用的康复。一起研讨还发现医治14 d后,调查组患者血浆内毒素、TNF-α及PCT水平比对照组下降更显着,提示肠道去污剂医治肝硬化可下降血浆内毒素、TNF-α及PCT水平,减轻肠源性内毒素血症,维护和改进其肠屏障功用。
总归,肝硬化患者选用肠道去污剂医治肝硬化能显着改进肝功用目标,使受损肝功用逐渐康复,并能下降血浆内毒素、TNF-α及PCT水平,然后减轻肠源性内毒素血症,维护及改进患者的肠道屏障功用,对肝硬化患者具有杰出的辅佐医治效果。
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[10]胡振斌,吕建林,邱华,等. 肝硬化中医辨证分型与血浆内毒素水平的相关性研讨[J]. 辽宁中医杂志,2012, 39(1):92-93.
[11]吴静黎,温帆渊,朱瑞芳,等. 肝硬化患者血清内毒素、TNF-α、IL-6检测的临床含义[J]. 现代医药卫生,2004, 20(8):602-603.
[12]堵一乔,徐 刚,杨振华. 肝硬化腹水患者血浆降钙素原水平的临床研讨[J]. 查验医学, 2012, 27(5):376-378.
[13]Mol M, Van Kan HJ, Schultz MJ, et al. Systermic tobramycin concentration during selective decontamination of the digestive tract in intensive care unit patients on continuous venovenous hemofiltration[J]. Intensive Care Med,2008,34(5):903-904.
[14]Hu HL, Gao M. Research advance in intestinal barrier function and evaluation index[J]. Chinese Journal of Animal Science,2012,48(17):78-82.
[15]Guzmn-dela Garza FJ, Gmara-Lemarroy CR, et al. Different patterns of intestinal response to injury after arterial,venous or arteriovenous occlusion in rats[J]. World J Gastroenterol,2009,15(31):3901-3907.
[16]黄宏春,王秀敏. 肠黏膜通透性改动对肝硬化自发性细菌性腹膜炎的影响[J]. 胃肠病学和肝病学杂志,2008,17(10):852-853.
[17]周福喜. 肠道去污联合微生态制剂医治晚期肝硬化的临床研讨[J]. 中华消化杂志,2009, 26(2):125-126.
[18]Zabielski R. Reefs in experimental gastroenterology-cyclic activities of the gastrointestinal tract[J]. J Physiol Pharmaco,2004,55(Suppl 2) :19-32.
[19]覃慧敏.肠道去污剂经不同途径给药对肝硬化患者肠黏膜通透性及血清内毒素水平的影响[J]. 我国全科医学,2012,15(6):674-676.
[20]王志勇. 肠道去污剂对肝硬化患者肠道屏障功用、内毒素水平及肝功用状况的影响[J]. 胃肠病学和肝病学杂志,2013,22(7):691-693.
(收稿日期:2014-01-03)
[4]李玉银,简燕婷. 肠道去污剂联合疗法在肝硬化患者医治中的效果[J]. 我国医学工程, 2013,21(3):101.
[5]中华医学会流行症寄生虫病学会修订. 病毒性肝炎防治计划[J].中华流行症学杂志,2000,19(6): 241-243.
[6]谭慧敏. 肝硬化患者肠黏膜通透性与Child-Pugh分级的相关性研讨[J]. 临床内科杂志,2011, 28(1):44-45.
[7]王波,宋怀宇,杨建荣. 肝病患者肠道屏障功用改动的研讨进展[J]. 临床肝胆病杂志, 2011, 27(8):893-896.
[8]Lin CY,Tsai IF,Ho YP,et al. Endotoxemia contributes to the immune paralysis in patients with cirrhosis[J]. J Hepatol,2007,46(5):816-826.
[9]杜兰霞,褚燕君,贾百灵. 肝硬化腹水患者血清二胺氧化酶、内毒素和IL-18水平的改动及其临床含义[J]. 有用医学杂志,2011,27(14):2547-2548.
[10]胡振斌,吕建林,邱华,等. 肝硬化中医辨证分型与血浆内毒素水平的相关性研讨[J]. 辽宁中医杂志,2012, 39(1):92-93.
[11]吴静黎,温帆渊,朱瑞芳,等. 肝硬化患者血清内毒素、TNF-α、IL-6检测的临床含义[J]. 现代医药卫生,2004, 20(8):602-603.
[12]堵一乔,徐 刚,杨振华. 肝硬化腹水患者血浆降钙素原水平的临床研讨[J]. 查验医学, 2012, 27(5):376-378.
[13]Mol M, Van Kan HJ, Schultz MJ, et al. Systermic tobramycin concentration during selective decontamination of the digestive tract in intensive care unit patients on continuous venovenous hemofiltration[J]. Intensive Care Med,2008,34(5):903-904.
[14]Hu HL, Gao M. Research advance in intestinal barrier function and evaluation index[J]. Chinese Journal of Animal Science,2012,48(17):78-82.
[15]Guzmn-dela Garza FJ, Gmara-Lemarroy CR, et al. Different patterns of intestinal response to injury after arterial,venous or arteriovenous occlusion in rats[J]. World J Gastroenterol,2009,15(31):3901-3907.
[16]黄宏春,王秀敏. 肠黏膜通透性改动对肝硬化自发性细菌性腹膜炎的影响[J]. 胃肠病学和肝病学杂志,2008,17(10):852-853.
[17]周福喜. 肠道去污联合微生态制剂医治晚期肝硬化的临床研讨[J]. 中华消化杂志,2009, 26(2):125-126.
[18]Zabielski R. Reefs in experimental gastroenterology-cyclic activities of the gastrointestinal tract[J]. J Physiol Pharmaco,2004,55(Suppl 2) :19-32.
[19]覃慧敏.肠道去污剂经不同途径给药对肝硬化患者肠黏膜通透性及血清内毒素水平的影响[J]. 我国全科医学,2012,15(6):674-676.
[20]王志勇. 肠道去污剂对肝硬化患者肠道屏障功用、内毒素水平及肝功用状况的影响[J]. 胃肠病学和肝病学杂志,2013,22(7):691-693.
(收稿日期:2014-01-03)
[4]李玉银,简燕婷. 肠道去污剂联合疗法在肝硬化患者医治中的效果[J]. 我国医学工程, 2013,21(3):101.
[5]中华医学会流行症寄生虫病学会修订. 病毒性肝炎防治计划[J].中华流行症学杂志,2000,19(6): 241-243.
[6]谭慧敏. 肝硬化患者肠黏膜通透性与Child-Pugh分级的相关性研讨[J]. 临床内科杂志,2011, 28(1):44-45.
[7]王波,宋怀宇,杨建荣. 肝病患者肠道屏障功用改动的研讨进展[J]. 临床肝胆病杂志, 2011, 27(8):893-896.
[8]Lin CY,Tsai IF,Ho YP,et al. Endotoxemia contributes to the immune paralysis in patients with cirrhosis[J]. J Hepatol,2007,46(5):816-826.
[9]杜兰霞,褚燕君,贾百灵. 肝硬化腹水患者血清二胺氧化酶、内毒素和IL-18水平的改动及其临床含义[J]. 有用医学杂志,2011,27(14):2547-2548.
[10]胡振斌,吕建林,邱华,等. 肝硬化中医辨证分型与血浆内毒素水平的相关性研讨[J]. 辽宁中医杂志,2012, 39(1):92-93.
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(收稿日期:2014-01-03)