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。     

GLP-2对实验性梗阻性黄疸小肠上皮细胞MLCK表达的影响

目的探讨类高血糖素多肽-2(GLP-2)对大鼠实验性梗阻性黄疸小肠上皮细胞肌球蛋白轻链激酶(MLCK)的影响。方法建立梗阻性黄疸大鼠模型,10d后对照组给予0.01mmol/LPBS0.5mL,实验甲组给予250g/(kg.d),实验乙组给予125g/(kg.d)的GLP-2溶液0.5mL,分别皮下注射,均为每天2次,连续7d后处死。并设假手术组。检测末端回肠黏膜形态学变化;采用免疫组化和Western blots法检测MLCK的分布和表达,并利用图像分析系统对Westernblots图像结果进行定量分析。结果梗阻性黄疸时小肠黏膜萎缩明显,肠绒毛短而稀疏。外源性补充GLP-2后小肠绒毛上皮结构有所恢复;实验甲组平均肠绒毛高度、黏膜厚度和隐窝深度与对照组相比分别上升27.1%,26.4%和25.3%(均P0.01)。梗阻性黄疸时对照组MLCK染色稀疏,分布不均。实验甲组的MLCK染色有所恢复,强阳性表达例数(8/10)较对照组(2/10)明显升高(P0.05),实验乙组(4/10)没有变化(P0.05)。Westernblot图像定量分析所得结果相同。实验甲组的绒毛高度的下降值与MLCK图像的吸光度的下降值呈正相关(r=0.62,P0.01)。结论梗阻性黄疸时小肠黏膜明显萎缩,外源性补充GLP-2能增强小肠黏膜上皮MLCK的分布和表达,恢复肠黏膜上皮的形态。     

胰高血糖素样肽-2对实验性梗阻性黄疸大鼠肠道屏障功能的保护作用

目的 探讨胰高血糖素样肽-2(GLP-2)对梗阻性黄疸模型大鼠肠道屏障功能的保护作用机制.方法 将72只SD大鼠随机分为3组:实验组(T组,n=24)、手术对照组(C组,n=24)和假手术组(SO组,n=24).T组和C组双重结扎胆总管,建立梗阻性黄疸模型;SO组开腹但不结扎胆总管.结扎后,T组腹腔注射GLP-2 (250 μg·kg-1·d-1),C组和SO组注射等体积0.01 mol/L的PBS溶液.于手术后第1、3、7天分别分批处死动物.应用RT-PCR技术半定量检测空肠黏膜GLP-2R mRNA的表达,应用免疫组织化学方法检测肠黏膜B细胞淋巴瘤/白血病基因-2(bcl-2)的表达.结果 T组肠黏膜GLP-2R mRNA的表达量比C组高,差异有统计学意义(P＜0.05),比SO组表达量稍低,差异无统计学意义(P＞0.05);C组肠黏膜bcl-2的表达于术后逐渐减少,差异有统计学意义(P＜0.05),且其表达量较SO组和T组少(P＜0.05),特别是第3、7天时,比SO组和T组降低更明显(P＜0.05).结论 GLP-2可以增加实验性梗阻性黄疸时肠黏膜细胞GLP-2R的表达,阻止肠黏膜细胞的凋亡,从而发挥保护肠道屏障功能的作用.     

胰高血糖素样肽-2对短肠大鼠残留小肠代偿的影响

目的研究胰高血糖素样肽-2(GLP-2)对短肠大鼠残留小肠形态及功能代偿的影响。方法将20只切除小肠75%的大鼠随机分成对照组和GLP-2组,术后1-5 d内自由进食。GLP-2组每日2次腹腔注射GLP-2(250μg·kg~(-1)·d~(-1))；对照组每日2次腹部皮下注射生理盐水0．5 ml；另设1组正常进食大鼠作空白对照。术后第6天行残留小肠黏膜形态学检测、细胞增殖核心抗原(PCNA)测定,钠葡萄糖共同转运体(SGLT1)和二肽转运体(PEPT1)的mRNA表达检测以及在体小肠循环灌流实验测定大鼠回肠的单位长度及单位重量的葡萄糖吸收率。结果GLP-2组残留小肠黏膜形态学指标、PCNA指数显著高于对照组；而小肠黏膜细胞凋亡显著低于对照组；残留回肠SGLT1和PEPT1的mRNA表达显著高于对照组；均P＜0．05。但两组灌洗段回肠每g湿重葡萄糖吸收率差异无统计学意义(P＞0．05)。结论GLP-2能刺激小肠黏膜上皮增生、抑制凋亡,促进短肠大鼠残留小肠黏膜的形态及功能代偿。     

外源性生长激素对梗阻性黄疸大鼠血白细胞介素-2及其受体的影响

梗阻性黄疸时体内过多的内毒素对免疫系统造成损害并导致感染，生长激素具有促进合成代谢，减轻肠黏膜屏障损伤，降低血内毒素水平的作用，并可进一步降低血肿瘤坏死因子α水平。本文拟探讨外源性生长激素对大鼠血白细胞介素-2(IL-2)及其受体的影响。     

重组胰高血糖素样多肽2对烧伤大鼠肠黏膜的保护作用

目的验证重组胰高血糖素样多肽2（GLP-2）对严重烧伤大鼠的肠道保护作用。方法将SD大鼠随机分为正常对照组；烧伤对照组；重组GLP-2治疗组（重组治疗组），烧伤后4h皮下注射重组GLP-2，100nmol·kg^-1·d^-1；化学合成GLP-2治疗组（合成治疗组），烧伤4h后皮下注射合成GLP-2，剂量同上。每组6只大鼠。伤后第7天检测各致伤组大鼠肠黏膜通透性、肠黏膜湿质量与肠段及躯壳质量比、肠黏膜蛋白含量以及观察肠道组织病理学变化，正常对照组观察指标相同。结果重组治疗组及合成治疗组与烧伤对照组[（0．350±0．040）mg／m1]比较，大鼠肠黏膜通透性明显降低（P〈0．01），分别为（0．250±0．026）、（0．243±O．008）mg／ml；肠黏膜湿质量与躯壳质量比及肠黏膜蛋白含量明显增加，重组治疗组大鼠肠黏膜蛋白含量为（57．9±2．8）mg／g，高于合成治疗组（48．9±4．1）mg／g。与正常对照组比较，各致伤组大鼠伤后第7天肠黏膜绒毛明显变短脱落、排列紊乱、基底层变薄。重组治疗组损伤较烧伤对照组有所减轻，与合成治疗组大鼠无明显区别。结论重组GLp02与合成GLP-2，能减轻烧伤大鼠肠道损伤，具有明显的肠道保护作用。     

Bcl-2基因在阻塞性黄疸大鼠肝细胞凋亡中的作用

目的:探讨Bcl-2基因对阻塞性黄疸大鼠肝细胞损害中细胞凋亡的调控作用。方法:采用胶原酶原位肝灌注法获取对照组大鼠肝细胞及阻塞性黄疸实验组术后3、7、14、21d大鼠的肝细胞,分别用RT-PCR检测Bcl-2mRNA的表达。分离对照组及实验组14d组大鼠的肝细胞行原代培养后,使用100μmol/L甘氨鹅脱氧胆酸钠(GCDC)作用于两组肝细胞24h后,用FCM法测定肝细胞的凋亡比率,用TUNEL技术进行肝细胞凋亡的原位检测。结果:(1)对照组大鼠肝细胞无Bcl-2mRNA表达,实验组术后7、14、21d组大鼠肝细胞均有Bcl-2mRNA表达;(2)GCDC作用两组大鼠肝细胞后,实验组比对照组肝细胞凋亡明显减少(P<0.001)。结论:在阻塞性黄疸过程中,大鼠肝细胞通过表达Bcl-2基因是抑制胆盐致肝细胞的凋亡作用的途径之一。     

胰高血糖素样肽-2对短肠大鼠残留小肠代偿的影响

目的　研究胰高血糖素样肽 2 (GLP 2 )对短肠大鼠残留小肠代偿的影响及机制。方法　 75 %小肠切除大鼠随机分成空白 (SB)组、生长激素 (GH )组和GLP 2组。术后 6d行残留回肠黏膜形态学检测、细胞增殖核心抗原 (PCNA)测定及原位末端标记 (INST法 )染色。结果　GLP 2组回肠黏膜形态学指标显著高于SB组 (P <0 .0 5 ) ,并且其黏膜厚度显著高于GH组 (P <0 .0 5 )。GLP 2组PCNA指数显著高于SB组 (0 .5 1± 0 .0 9与 0 .40± 0 .0 6比较 ,P <0 .0 5 ) ,但和GH组比较差异无统计学意义 (P >0 .0 5 )。GLP 2组细胞凋亡显著低于SB组 (67.7± 10 .1与 81.7± 12 .9比较 ,P <0 .0 5 ) ,但和GH组比较差异无统计学意义 (P >0 .0 5 )。结论　GLP 2能刺激小肠黏膜上皮增生 ,抑制凋亡 ,显著促进短肠大鼠残留小肠黏膜的形态代偿。     

胰高血糖素样肽-2对烧伤大鼠肠粘膜细胞增殖的影响

目的　探讨胰高血糖素样肽 2 (GLP 2 )对烧伤大鼠肠粘膜细胞增殖及肠粘膜结构的影响。　方法　 5 5只Wistar大鼠随机分为烧伤组、GLP 2组 (烧伤后经GLP 2处理 ,2 0 0 μg/kg ,2次 /d腹腔注射 )与正常对照组。前两组动物于 30 %TBSAⅢ度烧伤后 6、12h及 1、3、5d分别处死 ,另处死正常对照组大鼠。检测各组增殖细胞核抗原 (PCNA)、细胞周期蛋白CyclinD的表达情况以及血浆二胺氧化酶 (DAO)的活性 ,并行肠粘膜组织学观察。　结果　与正常对照组比较 ,烧伤组伤后 6、12hPCNA表达稍有增强 ,伤后 1d减弱 ,3d时最低 ,5d时仍低于正常 ;GLP 2组PCNA表达的变化在伤后早期与烧伤组基本一致 ,但伤后 3、5d时强于烧伤组。烧伤组大鼠肠粘膜CyclinD蛋白在伤后 6、12h略有升高 ,但 1d时迅速下降至伤前的 4 0 % ,而GLP 2组CyclinD蛋白表达在伤后 1、3、5d高于烧伤组。大鼠烧伤后血浆DAO活性明显升高 ,经GLP 2治疗 5d后该指标明显降低 (P <0 .0 1)。组织学观察见GLP 2组肠绒毛排列较为规则 ,长短较一致 ,未见明显的上皮脱落。　结论　大鼠烧伤后腹腔给予外源性GLP 2能减轻肠粘膜损伤 ,其机制可能与GLP 2使PCNA、ClyclinD表达增加、促进受损肠粘膜细胞增殖有关。     

青藤碱对梗阻性黄疸大鼠肝损伤保护作用研究

目的:探讨青藤碱对梗阻性黄疸大鼠肝脏损伤的保护作用。方法:将32只大鼠随机均分为假手术组,模型组和高、低2个剂量青藤碱干预组。除假手术组外,其余各组大鼠均行胆总管结扎。术后第1天开始,2个青藤碱干预组大鼠分别给予40 mg/kg和80 mg/kg青藤碱灌胃,假手术组和模型组给予等体积的生理盐水灌胃,1次/d。第8天处死各组大鼠,取腹主动脉血测血清总胆红素(TBIL),直接胆红素(DBIL),谷丙转氨酶(AST),谷草转氨酶(ALT)水平,取右肝用试剂盒测肝组织中丙二醛(MDA),髓过氧化物酶(MPO)含量,总抗氧化能力(T-AOC),实时荧光定量PCR法测转化生长因子β1(TGF-β1)mRNA的表达,取左肝做HE和免疫组织化学染色分别检测肝组织病理学和TGF-β1蛋白的表达。结果:除假手术组外,各组大鼠肝组织均出现不同程度的病理改变,其中2个青藤碱干预组大鼠肝组织病变明显轻于模型组。与假手术组比较,各组大鼠血清TBIL,DBIL,ALT,AST水平明显增高;肝组织MDA,MPO含量明显升高,T-AOC明显降低;肝组织TGF-β1的蛋白和基因表达明显增高(均P<0.05)。模型组上述指标的变化程度均较2个青藤碱干预组明显(均P<0.05),而高低2个青藤碱干预组间上述指标均无统计学差异(均P>0.05)。结论:青藤碱对梗阻性黄疸大鼠肝脏的损伤具有保护作用,其机制可能与降低TGF-β1的表达有关。     

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。     

人重组生长激素对梗阻性黄疸大鼠肠源性细菌/内毒素移位的影响

目的探讨人重组生长激素(rhGH)减轻梗阻性黄疸时肠源性细菌及内毒素移位的作用及机制。方法Wister大鼠42只分为3组假手术组(SO组)、胆总管结扎组(BDL组)及rhGH治疗组(rhGH组)。实验1周后检测各组肝功指标的变化及血浆内毒素水平,取肝、肾、肠系膜淋巴结等肠道外器官组织做细菌培养,电镜观察末端回肠黏膜变化。结果rhGH组多项肝功指标较BDL组明显改善,rhGH组血浆内毒素水平为(0·38±0·03)EU/ml,较BDL组的(0·65±0·04)EU/ml明显降低(P<0·01),与SO组的(0·30±0·02)EU/ml比较无显著差异(P>0·05)。BDL组肝、肾、肠系膜淋巴结中细菌移位率高于另两组,其中肠系膜淋巴结细菌移位率为64·29%,明显高于SO组及rhGH组(P<0·05),后两组之间各部位细菌检出率差别无显著性(P>0·05)。电镜显示BDL组肠黏膜上皮细胞坏死,细胞核固缩,线粒体肿胀变性,内质网明显扩张。rhGH组肠黏膜上皮改变较BDL组明显减轻,接近SO组所见。结论应用rhGH可保护梗阻性黄疸时小肠黏膜屏障功能,减少肠源性细菌/内毒素移位的发生。     

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.     

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.     

热射病对大鼠小肠上皮紧密连接occludin蛋白的影响

目的 观察热射病大鼠小肠上皮屏障通透性的改变,并通过观察肠上皮细胞紧密连接形态及肠上皮细胞紧密连接蛋白occludin蛋白表达的变化,初步探讨热射病对肠上皮屏障通透性的影响及机制.方法 将SD大鼠随机分为两组,每组10只(n=10),热射病组及常温对照组,制备热射病大鼠模型,动物麻醉后放入42 ℃恒温箱热暴露50 mi...     

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     

Effects of obstructive jaundice on the peripheral nerve: an ultrastructural study in rats

Obstructive jaundice (OJ) and hepatic disorders have been shown to be associated with peripheral neuropathy in several clinical studies. The study evaluated the effect of OJ on the ultrastructure of the rat sciatic nerve. In the OJ group, jaundice was created by ligation of common bile duct in Wistar-Albino rats. In the sham-operated control group the same procedure was performed without ligation of the bile duct. On day 7, all rats were re-operated and sciatic nerves were explored to harvest 2-cm-long nerve segments for quantitative and qualitative histopathological analysis by light and electron microscopy. Bilirubin was measured on serum samples. Bilirubin levels were significantly higher in jaundiced rats compared with that of controls (8.46 +/- 0.45 vs. 0.80 +/- 0.14 mmol/l, means +/- SD, p < 0.01). Control nerves did not show anything other than the normal histology. In the OJ group, degenerative changes such as irregularities, thinning, ruffling and invaginations, irregularshaped bodies, vacuolizations and focal segmental demyelination were observed in the myelin sheath. Myelin clusters were noted in the axoplasm. A varying degree of swelling was noted in the nucleus and cytoplasm of the Schwann cells. Morphometric analysis of specimens obtained from sciatic nerves showed that myelin injury (370.9 +/- 51.3 vs. 11.6 +/- 0.5 axons), axonal edema (142.1 +/- 24.2 vs. 10.6 +/- 0.5 edematous axons) and Schwann cell degeneration (50.3 +/- 11.6 vs. 3.2 +/- 0.2 Schwann cells) was significantly higher in the jaundiced rats than in the control group (p < 0.01). The ultrastructural alterations spotted in the rat peripheral nerve were attributed to hyperbilirubinemia and increased concentrations of several neurotoxic substances released from the Kupffer cells in OJ. Neuropathy in jaundiced patients seems to result from accompanying degenerative changes in the peripheral nervous system. However, the exact nature and initiating factors of this nerve injury remains to be unveiled.