梗阻性黄疸时脾切除对肠黏膜屏障影响的实验研究

目的 探讨脾脏在梗阻性黄疸(阻黄)中对肠黏膜屏障的作用及其机制.方法 50只Wistar大鼠随机分组,阻黄组开腹结扎胆总管;阻黄+脾切除组,同时切除脾脏.术后7d观察血浆内毒素水平的变化,用乳果糖/甘露醇(L/M)比值检测肠黏膜通透性;采用免疫组织化学、Western印迹检测末端回肠紧密连接蛋白闭锁小带-1(ZO-1)、闭锁蛋白的表达,并利用图像分析系统对Western印迹图像进行定量分析.结果 阻黄+脾切除后L/M的比值和血浆内毒素水平较阻黄组明显下降(均P=0.001).与阻黄组相比,阻黄+脾切除组的平均肠绒毛高度和隐窝深度有所上升(P=0.019、0.001).免疫组化显示术后7 d阻黄组ZO-1蛋白强阳性表达数(6/18)下降明显(P=0.021),阻黄+脾切除组(8/17)染色较阻黄组变化不大;闭锁蛋白的染色阻黄+脾切除组强阳性表达(7/17)高于阻黄组(4/18)(P=0.026).通过对Western印迹图像进行定量分析也得出同样的结论.结论 阻黄后肠黏膜通透性增加,肠黏膜屏障受损.同时切除脾脏,肠紧密连接蛋白成分的数量和分布改变,肠黏膜屏障的损害减轻.

Abstract：

Objective To investigate the effects of splenectomy on the intestine mucosa barrier in rats with obstructive jaundice. Methods 50 Wistar rats were divided randomly into the obstructive jaundice group (OJ), in which the animals underwent operation to ligate common bile duct, and the obstructive jaundice + splenectomy group (OJ+ S). Seven days post-operation, plasma endotoxin levels were detected. Intestinal mucosa permeability was measured by the ratios of lactulose and mannitol (L/M). Immunohistochemistry and Western blot were used to examine the expression of tight junction proteins (ZO-1 and occludin) in the distal ileum mucosa. Western blots images were analyzed quantitatively. Results Average ratios of L/M and plasma endotoxin were decreased obviously in the OJ+S group compared to those in the OJ group (all P=0. 001). Compared with the OJ group, the average intestinal villus height and mucosa thickness were upgraded somewhat in the OJ + S group (P = 0.019, 0. 001 ). By immunohistochemistry staining seven days post-operation, same comment as above the amounts of strong positive expression of ZO-1 were significantly decreased in the OJ group (6/18, P-0. 021). There wewas no difference between the OJ+S group(8/17) and the OJ group.The amount of strong positive expression of occludin was higher in the OJ + S group than that of the OJ group(10/17 vs 4/18, P= 0. 026). The same outcomes were obtained by quantitative Western blot images. Conclusion The intestinal epithelial permeability was increased in rats with obstructive jaundice,and intestinal barrier was damaged. After excising spleen, the amount and distribution of tight junction proteins were changed and the impairment of intestinal barrier was abated.     

乌司他丁在梗阻性黄疸时保护肠黏膜屏障功能的实验研究

梗阻性黄疸引起肝细胞的损伤，释放多种细胞因子及炎性介质致肠黏膜屏障损伤，肠道细菌移位产生肠源性内毒素血症，可导致肝肾等多脏器功能衰竭。乌司他丁（ulinastatin，UTI）有抑制多种水解酶活性，抑制细胞因子和炎性介质的释放，本研究探讨UTI在梗阻性黄疸大鼠模型中保护肠黏膜屏障功能的作用机制。     

胆汁外引流对梗阻性黄疸大鼠肠黏膜紧密连接影响的实验研究

目的探讨胆汁在保护小肠黏膜屏障中的作用及其机理。方法 50只Wistar大鼠随机分为对照组(n=10)、梗阻性黄疸(阻黄)组(n=20)及外引流组(n=20)。造模10 d后测定血浆内毒素水平;取末端回肠黏膜组织,光镜下观察黏膜形态改变并测量相关指标,采用免疫组化及Western blot法检测紧密连接相关蛋白(闭锁小带蛋白-1及闭锁蛋白)的表达。结果阻黄组小肠黏膜萎缩明显,其肠绒毛高度、黏膜厚度和隐窝深度与对照组相比分别下降27.8%、21.7%和25.4%(P=0.001、0.001、0.040);外引流组各指标较对照组无明显变化(P=0.050、0.070、0.080),而明显优于阻黄组(均P=0.001)。阻黄组的血浆内毒素水平高达(1.49±0.27)EU/ml,明显高于对照组的(0.27±0.09)EU/ml(P=0.001);外引流组为(0.91±0.25)EU/ml,高于对照组而低于阻黄组(P=0.001)。免疫组化结果显示,闭锁小带蛋白-1的强阳性表达从对照组的7/10例降至阻黄组的6/20例(P=0.040),闭锁蛋白则从8/10例降至7/20例(P=0.020);而外引流组分别为8/20例(P=0.100、0.210)和9/20例(P=0.060、0.200),与前2组相比差异均没有统计学意义。Western blot分析显示,阻黄组闭锁小带蛋白-1和闭锁蛋白的表达水平较之对照组均明显下降(P=0.001、0.010);外引流组高于阻黄组(P=0.005、0.014),而闭锁小带蛋白-1的表达水平低于对照组(P=0.001),闭锁蛋白的表达与对照组比较差异无统计学意义(P=0.062)。结论肠道内胆汁缺乏会破坏肠紧密连接相关蛋白的成分,损伤肠黏膜屏障;胆道梗阻时由于存在其他因素,肠黏膜屏障损伤更严重。胆汁在保护肠黏膜屏障中具有重要作用。     

硬膜外复合全身麻醉对梗阻性黄疸术后肠屏障功能的影响

目的探讨硬膜外复合全身麻醉对梗阻性黄疸患者术后肠屏障功能的影响。方法选择梗阻性黄疸拟行手术治疗患者40例,男15例,女25例,年龄26~65岁,ASAⅠ~Ⅲ级,手术时间90~320min,血清总胆红素(TBIL)水平100μmol/L。所有患者随机分为全凭静脉麻醉组(GA组)和硬膜外复合全麻组(GE组),每组20例。GA组患者面罩吸氧后快速诱导气管插管行全身麻醉,GE组患者取左侧卧位行T8~9或T9~10间隙硬膜外穿刺并置管,改平卧位后予以2%利多卡因5ml试验量,5min确认无麻醉并发症及其他异常后行全身麻醉。于入手术室后(T1)、术毕(T2)、术后24h(T3)和术后48h(T4)分别采集外周静脉血,采用ELISA法测定血浆D-乳酸(D-LA)浓度;PCR技术定性检测大肠杆菌特异性β-半乳糖苷酶基因BG;提取血浆标本中的细菌DNA,进行PCR扩增,凝胶电泳后扫描凝胶并分析结果。结果与T1时比较,T2~T4时两组血浆D-LA浓度明显逐步升高(P0.05);T2~T4时GA组D-LA浓度明显高于GE组(P0.05)。PCR技术定性检测大肠杆菌特异性半乳糖苷酶基因BG,扩增长度为762bp。T1时两组患者大肠杆菌DNA检测结果均为阴性,术后两组患者大肠杆菌DNA阳性例数随时间依次增多,且T4时GA组明显高于GE组(P0.05)。结论与全凭静脉麻醉比较,硬膜外复合全身麻醉能够减轻梗阻性黄疸患者术后肠屏障功能的损伤。     

含谷氨酰胺白TPPN对梗阻性黄疸大鼠肠黏膜形态学的影响

目的：研究不同氨基酸配方的TPN对梗阻性黄疸大鼠肠黏膜形态学的影响。材料与方法：封闭群SD大鼠45只，平均分为5组。A组；假手术经口饮食对照组，B组：胆总管结扎经口饮食对照组；C至E组为胆总管结扎加TPN组，其中C组以15－氨基酸800为氮源，D组以Novamin为氮源，E组以Glamin为氮源，E组以Glamin为氮源。各组TPN为等氮，等热量。分别于TPN0h,72h和120h处死实验大鼠。作空肠和结肠光镜检查及绒毛高度的图象分析，并对空肠作电镜检查。结果：C组大鼠的空肠和结肠绒毛高度均低于相应的饮食组，空肠微绒毛稀疏，缺如：D组大鼠的空肠绒毛高度低于相应的饮食组，结肠绒毛高度则高于相应的饮食组，而E组大鼠，其空肠和结肠绒毛高度与相应的饮食组无显著差异，明显高于C组和D组，空肠微绒毛结构保持较好。结论：胆总管结扎术后，可造成大鼠肝外梗阻性黄疸，并对其空肠及结肠黏膜萎缩具有独立影响作用。提供平衡氨基酸溶液的TPN可有效促进机体对外源性氨基酸的利用而减轻标准TPN对肠黏膜的负面影响。富含Gln的TPN有助于预防标准TPN引起的肠道黏膜萎缩。     

缺氧条件下环磷酸腺苷对肠黏膜屏障功能的调控研究

目的探讨缺氧条件下环磷酸腺苷（cAMP）水平的变化对肠黏膜屏障功能的影响。方法采用人结肠癌Caco．2细胞建立肠上皮细胞缺氧模型,分为常氧组、常氧加Forskolin组、缺氧8h组和缺氧8h加SQ22536（腺苷酸环化酶抑制剂）组。采用cAMP检测试剂盒,检测实验各组cAMP水平的变化;RT-PCR及Westernblot方法分别检测各组肠上皮紧密连接蛋白claudin-1和occludin的mRNA和蛋白表达水平的变化：Millipore电阻抗系统法检测各组肠上皮细胞跨上皮电阻（TER）的变化情况。结果缺氧8h组肠上皮cAMP含量较常氧组明显升高[（6．30±0．50）pmol／L比（2．38±0．18）pmol／L,P〈0．01],而claudin．1和occludin的mRNA及蛋白表达水平均明显降低（均P〈0．05）,TER值下降了6．30±0．64（P〈0．01）。与缺氧8h组相比,缺氧8h加SQ22536组肠上皮cAMP含量明显降低[（2．12±0．23）pmol／L比（6．30±0．50）pmol／L,P〈0．01],claudin-1和occludinmRNA及蛋白表达水平明显升高（P〈0．01）,TER值升高了32．96±2．16（均P〈0．05）。结论缺氧条件下cAMP水平升高,而下调cAMP水平可增加肠道紧密连接蛋白claudin-1及occludinmRNA及蛋白水平的表达,从而减轻缺氧对肠上皮屏障的损伤。     

梗阻性黄疸大鼠肠黏膜上皮紧密连接蛋白和MLCK的研究

目的:探讨梗阻性黄疸肠黏膜屏障破坏的机制。方法:建立梗阻性黄疸大鼠的动物模型,分别于胆管结扎10 d和20 d后，采用免疫组化、Western blot方法检测末端回肠黏膜的紧密连接蛋白成员ZO-1和Occludin与肌球蛋白轻链激酶（MLCK）的分布和表达。结果:正常回肠黏膜层ZO-1和Occludin的分布相似，主要位于上皮细胞的边缘，细胞膜顶端，沿绒毛下方均匀连续分布；MLCK主要分布在细胞浆内。梗阻性黄疸时ZO-1和Occludin分布不均, 染色变淡，线条模糊，边缘粗糙有毛刺状突起；MLCK分布散乱，染色稀疏。与对照组相比20 d组和10 d组的ZO-1，Occludin，MLCK数量明显减少，强阳性表达率分别从70.0 %，80.0 %，70.0 %降至10 d组的28.6 %，28.6 %，28.6 % (均P＜0.05)和20 d组的ZO-1从10 d 组的28.6 %降至14.3 %, 35.7 %, 21.4 % (均P＜0.05)。20 d 组的ZO-1下降较10 d组更为明显（P<0.05）, 而Occludin和MLCK变化不明显。Western blot检测的结果与之相似。结论:梗阻性黄疸时大鼠小肠黏膜上皮ZO-1，Occludin，MLCK分布紊乱，表达下降，小肠黏膜上皮屏障的完整性破坏。     

GLP-2对实验性梗阻性黄疸小肠上皮细胞紧密连接的调控

目的:探讨类高血糖素多肽-2（GLP-2）对实验性梗阻性黄疸小肠上皮细胞紧密连接的调控。方法:建立梗阻性黄疸大鼠模型，造模后10d随机分组，每组10只。黄疸组皮下注射0.01 mmol/LPBS 0.5 mL，实验甲组腹腔注射250 g/（kg·d），实验乙组腹腔注射125g/（kg·d）的GLP-2溶液0.5 mL，每天2次，连续7 d后处死。另设正常对照组，用免疫组化及Western blots检测末端回肠黏膜紧密连接蛋白ZO-1,Occludin及Claudin-1, Claudin-4的分布和表达，并用图像分析系统对Western blots图像进行定量分析。结果:正常情况下ZO-1,Occludin和Claudin-1染色强阳性率分别为70.0%,80.0%和70.0%。梗阻性黄疸时ZO-1和Occludin分布不均，染色变淡，线条模糊。补充外源性GLP-2后，实验甲组的ZO-1,Occludin和Claudin-1染色有所恢复，且强阳性表达率分别从黄疸组的20.0%，30.0%和20.0%升至实验甲组的80.0%,90.0%和80.0% (均P<0.05)；Claudin-4表达和分布变化不明显。实验乙组对紧密连接蛋白无影响。Western blots图像定量分析得到相同的结果。 结论:梗阻性黄疸时，补充GLP-2可影响小肠黏膜上皮紧密连接蛋白的分布和表达；提示GLP-2能恢复和维持小肠黏膜上皮屏障的完整性。     

帕瑞昔布钠对脓毒症小鼠肠黏膜屏障的保护作用

目的研究帕瑞昔布钠对脓毒症小鼠肠黏膜屏障功能的影响及可能机制。方法 21只C57BL/6小鼠随机分为三组:假手术组(Sham组)、脓毒症模型组(CLP组)、脓毒症模型+帕瑞昔布钠2mg/kg治疗组(P组),每组7只。术后24h用襻环结扎法检测各组小鼠小肠通透性。另21只C57BL/6小鼠随机分为三组,分组及治疗同前,术后24h处死小鼠,收集小鼠回肠。小肠组织行HE染色观察肠病理损伤。采用Western bolt法检测小肠ZO-1、Occludin、Claudin-1等紧密连接蛋白的表达。采用ELISA法检测小肠黏膜IL-6、PGE2的浓度。结果与Sham组比较,CLP组小鼠小肠明显损伤,门静脉血内FD4浓度明显升高,小肠黏膜内ZO-1、Occludin、Claudin-1蛋白表达明显减少、IL-6与PGE2浓度明显升高(P0.05)。与CLP组比较,P组小鼠小肠损伤明显减轻(P0.05),门静脉血内FD4浓度明显降低(P0.05),小肠黏膜内各蛋白表达水平明显增加、IL-6与PGE2浓度明显降低(P0.05)。结论帕瑞昔布钠治疗可以明显降低脓毒症导致的肠黏膜屏障功能损伤,其机制可能与降低肠组织炎症水平,增加肠紧密连接蛋白表达相关。     

不同营养方式对梗阻性黄疸大鼠肠紧密连接蛋白的影响

目的 观察肠内营养(EN)及肠外营养(PN)对阻塞性黄疸(OJ)大鼠小肠紧密连接蛋白的影响.方法 将50只Wistar大鼠随机分5组,EN组和PN组给予等热量等氮量营养.7 d后采用免疫组织化学和Western blot法检测各组末端回肠黏膜的闭锁小带-1(ZO-1)、闭锁蛋白(Occludin)与肌球蛋白轻链激酶(MLCK)的表达,并对Western blot图像进行定量分析.结果 正常回肠黏膜ZO-1和Occludin沿绒毛下方均匀连续分布,MLCK主要分布在细胞质内.阻黄时ZO-1、Occludin和MLCK分布散乱,染色稀疏.PN组的ZO-1、Occludin和MLCK的强阳性染色数由阻黄组的2、2、1例升至4、5、3例(P均>0.05),而EN组的强阳性染色数分别上升为7、6、5例(P均<0.05).通过对Western blot显影图像进行定量分析,EN组和PN组的ZO-1的灰度值较阻塞性黄疸组明显上升(均P<0.05);Occludin和MLCK的灰度值在EN组上升(P<0.05),PN组没有变化.结论 梗阻性黄疸时大鼠小肠黏膜上皮ZO-1、Occludin和MLCK分布紊乱,表达下降.肠内、外营养均能够恢复受损的紧密连接蛋白,肠内营养的作用更强.     

不同胆汁引流方式对梗阻性黄疸大鼠肠黏膜屏障功能的影响及机制

目的：探讨不同胆汁引流方式对梗阻性黄疸（OJ）大鼠肠黏膜功能的影响及其机制。 方法：将60只SD大鼠采用胆总管结扎法制作OJ模型,1周后随机均分为无引流组（不行胆汁引流术）,内引流组（行胆汁内引流术）和外引流组（行胆汁外引流术）,引流时间1周。以20只假手术大鼠为对照组,实验共2周,结束时分别用ELISA法和Western blot法检测各组血清内毒素水平和小肠黏膜组织闭锁蛋白（occludin）及闭锁小带蛋白1（ZO-1）的表达,并观察小肠黏膜组织形态学改变。 结果：大鼠造模后出现明显的OJ表现,二次手术后,内引流组大鼠一般情况明显好于无引流组和外引流组。无引流组和外引流组OJ大鼠血清内毒素水平明显升高,与对照组比较,差异均有统计学意义（均P<0.01）,而无引流组与外引流组间内毒素水平差异无统计学意义（P>0.05）;内引流组OJ大鼠血清内毒素水平较无引流组和外引流组明显下降（均P<0.01）,与对照组水平无统计学差异（P>0.05）。与对照组比较,无引流组和外引流组OJ大鼠小肠黏膜组织occludin及ZO-1蛋白表达均明显降低（均P<0.01）,且外引流组两者表达水平降低较无引流组更为明显（均P<0.01）;内引流组OJ大鼠的occludin及ZO-1的表达水平明显高于无引流组和外引流组（均P<0.01）,且基本接近对照组（均P>0.05）。病理学观察显示,无引流组和外引流组OJ大鼠肠黏膜结构破坏,大量或中量炎性细胞浸润,而内引流组OJ大鼠组肠黏膜结构完整,仅见少量炎性细胞浸润。 结论：胆汁内引流对OJ大鼠肠黏膜屏障具有保护作用,其机制可能与胆汁维持肠黏膜上皮细胞间紧密连接相关蛋白的表达有关。     

生长激素对肠缺血-再灌注肠粘膜屏障功能的保护作用

目的 研究生长激素对肠缺血—再灌注肠粘膜屏障的保护作用。方法 观察小肠缺血—再灌注24h小肠粘膜形态学，腹腔淋巴结细菌培养、门静脉内毒素水平、小肠粘膜细胞凋亡的改变及生长激素对其改变的影响。结果 小肠缺血—再灌注24h，小肠粘膜细胞凋亡增加，绒毛高度和数量显著降低，门静脉内毒素水平升高，腹腔淋巴结细菌培养阳性升高；生长激素能显著改善上述改变。结论 生长激素对肠缺血—再灌注肠粘膜屏障具有明显保护作用。     

The effect of pentoxifylline on the healing of intestinal anastomosis in rats with experimental obstructive jaundice

The aims of this study were (1) to investigate the effect of experimental obstructive jaundice on the healing of intestinal anastomosis, and (2) to investigate the effect of pentoxifylline on the healing of intestinal anastomosis in rats with obstructive jaundice. Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after this operation, either pentoxifylline or isotonic saline solution was administered intraperitoneally to these jaundiced rats and controls, and then intestinal anastomosis was performed. The concentrations of serum tumor necrosis factor α (TNF-α) and serum triglyceride of jaundiced and nonjaundiced rats were measured, and the quality of healing was evaluated by measuring the bursting preasure and hydroxyproline content of the anastomoses on the fifth and tenth days of anastomotic healing. Obstructive jaundice resulted in an impaired wound healing of the intestinal anastomosis in the rats. The administration of pentoxifylline to the jaundiced rats resulted in better anastomotic wound healing. The beneficial effects of pentoxifylline on anastomotic healing in rats with obstructive jaundice was attributed to its inhibitor effect on the endotoxin-induced TNF-α release from macrophages and monocytes, and the stabilizing effect on the neutrophils. Received: March 29, 1999 / Accepted: March 24, 2000     

阻塞性黄疸大鼠肠黏膜屏障功能变化及力肽的治疗作用

目的探讨阻塞性黄疸大鼠肠黏膜屏障功能变化以及力肽的治疗作用。方法将36只Wistar大鼠随机分成胆管结扎组（BDL）、假性手术组（SL）、胆管结扎＋力肽治疗组（Dipeptiven）3组,分别于术后24h、72h、1周和2周测定血浆内毒素值（Endotoxin,ET）,并于2周后作细菌移位率和肠黏膜组织学检查。结果BDL组厌氧菌移位阳性率（58．33％）及各时间点血浆ET值显著高于SL组（0）和Dipeptiven组（8．33％）（P〈0．01）,Dipeptiven组在各时间点血浆ET值较BDL组显著降低（P〈0．01）。组织学检查显示,BDL组肠黏膜发生了实质性损害。结论阻塞性黄疸时肠黏膜屏障损害可能促进肠道细菌移位,导致感染易感性增高。而力肽可改善受损小肠黏膜结构及减轻肠道细菌移位。     

The effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with experimental obstructive jaundice

Purpose  Intestinal anastomotic healing is a complex procedure in which several mediators and cytokines play roles. Calcitonin gene-related peptide is an important neuropeptide in inflammation. In this study we aimed to investigate the effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with obstructive jaundice. Materials and methods  Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after the operation, intestinal anastomosis was performed, and either calcitonin gene-related peptide or 0.9% NaCl was administered intraperitoneally to these jaundiced rats and controls. The concentrations of serum tumor necrosis factor-α (TNF-α) and triglyceride levels of all rats were measured, and healing of the anastomosis was evaluated by measuring the bursting pressure and hydroxyproline content on the 7th postoperative day. Results  Calcitonin gene-related peptide was found to have positive effects on healing of the anastomosis by inhibiting the effects of TNF-α and increasing the bursting pressure and hydroxyproline content of the anastomosis. Conclusion  Calcitonin gene-related peptide increases anastomotic wound healing in experimental anastomosis in the presence of obstructive jaundice in rats.     

谷氨酰胺对饥饿大鼠肠黏膜屏障功能的保护作用

目的探讨谷氨酰胺对饥饿大鼠肠黏膜屏障功能的保护作用。方法90只健康雄性SD大鼠,随机分为正常对照组(C组,n=10)、全饥饿组(S组,n=40)和谷氨酰胺组(G组,n=40),S、G组随机分为为饥饿3、5、7、9d亚组(n=10)。实验期间无饲料供应,自由摄水。G组给予谷氨酰胺1．0 g·kg-1·d-1水溶液灌胃,每天一次。取小肠组织,光镜下观察肠黏膜的形态改变,并观察细胞凋亡情况,测定小肠组织匀浆中一氧化化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果饥饿可以导致小肠黏膜损伤,凋亡细胞增加,小肠NO、MDA含量增加,SOD活性降低,谷氨酰胺可减弱饥饿诱导的上述改变(P<0．05或0．01)。结论谷氨酰胺对饥饿大鼠肠黏膜屏障功能有保护作用。     

氨基胍对梗阻性黄疸大鼠治疗作用的实验研究

目的 探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对梗阻性黄疸大鼠的治疗作用及作用机制.方法 雄性Wistar大鼠40只,随机分为正常对照组、假手术组、黄疸组、氨基胍治疗组4组,每组10只.通过测定治疗前后肝功、血胆红素、内毒素、乳酸、肝组织丙二醛水平,以及通过对肝脏、小肠的形态学分析来探讨氨基胍对梗阻性黄疽大鼠的治疗作用.结果 血浆内毒素和血清乳酸、肝组织丙二醛随着胆道梗阻时间的延长逐步升高,并伴随着肝脏小肠病理形态学的改变.氨基胍治疗组各项指标显著低于对照组,并能改善肝组织及小肠病理形态.结论 氨基胍(AG)可通过减轻脂质过氧化与内毒素血症发挥保护肝脏及小肠的作用,为治疗梗阻性黄疸患者提供了一种新的思路和方法.

Abstract：

Objective To evaluate the therapeutic effect and mechanism of specific inducible nitric oxide synthase(iNOS)aminoguanidine(AG)in rats with obstructive jaundice.Methods Forty male Wistar rats were divided randomly into four groups: normal control group, sham operation group, obstructive jaundice group and aminoguanidine therapeutic group.Each group had 10 rats.We assayed levels of liver function,hemobilirubin, endotoxin,lactic acid and malondialdehyde before and after therapy, and we also analyzed pathology of the liver and small intestine.Then we could explore the therapeutic effect of AG in rats with obstructive jaundice.Results The levels of endotoxin,lactic acid and malondialdehyde in blood increased progressively along with the pathological changes of the liver and small intestine.Each of the AG group parameters was significantly lower, and the pathological changes of liver and small intestine were improved.Conclusion AG could protect liver and small intestine by attenuating lipid peroxidative and endotoxemia,and provide a new way to cure obstructive jaundice.     

阻塞性黄疸大鼠小肠中组织细胞间粘附分子-1的表达

目的　探讨组织细胞间粘附分子 1 (ICAM 1 )在阻塞性黄疸小肠粘膜损伤中的表达及其作用。方法　建立阻塞性黄疸模型 ,于胆管结扎 7、1 4d两个时相点分别检测小肠组织中I CAM 1表达、髓过氧化物酶 (MPO)变化 ,观察小肠组织结构的病理改变。结果　在 7、1 4d两个时相点 ,阻黄组 (BDL组 )MPO活性明显增强 (2 .851± 1 .2 2 0 ,4.92 7± 1 .371 ,P <0 .0 5) ,肠粘膜结构明显受损 ;ICAM 1表达主要在小肠粘膜上皮细胞 ,其表达强度随梗阻时间延长而增强 (P <0 .0 5) ,与MPO变化、病理结构改变一致。结论　在阻塞性黄疸大鼠中 ,ICAM 1表达增强与小肠粘膜损伤的发生有关。