小肠移植急性排斥反应期移植肠白细胞介素2受体和细胞间粘附分子1的表达

目的　探讨移植肠白细胞介素２ 受体（ Ｉ Ｌ２ Ｒ） 和细胞间粘附分子１（ Ｉ Ｃ Ａ Ｍ１） 的表达在小肠移植排斥反应中的意义及诊断价值。方法　选用近交系大鼠 Ｆ３４４／ Ｎ 和 Ｗｉｓｔａｒ／ Ａ 进行全小肠异位移植,实验分４ 组,第１ 组： Ｗｉｓｔａｒ;第２ 组： Ｗｉｓｔａｒ→ Ｗｉｓｔａｒ ;第３ 组： Ｆ３４４ → Ｗｉｓｔａｒ;第４ 组： Ｆ３４４ → Ｗｉｓｔａｒ＋环孢霉素 Ａ（６ ｍｇ·ｋｇ － １·ｄ － １） 。术后第３ 、５ 、７ 天取各组动物移植肠标本进行病理学检查,应用免疫组化技术（ Ｓ Ｐ 法） 检测移植肠 Ｉ Ｌ２ Ｒ 和 Ｉ Ｃ Ａ Ｍ１ 的表达。结果　病理学检查显示第３ 组大鼠在术后第３ 、５ 、７天分别符合轻、中、重度排斥,第２ 、４ 组无明显排斥征象。第３ 组 Ｉ Ｌ２ Ｒ 表达在术后均非常显著高于其他３ 个对照组;第３ 组 Ｉ Ｃ Ａ Ｍ１ 表达在术后第３ 、５ 天较相似,尤其在上皮细胞表现为强阳性,并显著高于第１ 组。但第２ 、４ 对照组 Ｉ Ｃ Ａ Ｍ１ 表达也较高,第３ 组仅在术后第３ 天 Ｉ Ｃ Ａ Ｍ１ 评分显著高于第２ 组。结论　 Ｉ Ｌ２ Ｒ 和 Ｉ Ｃ Ａ Ｍ１ 阳性细胞在小肠移植排斥反应过程中发挥重要作用。应用单克隆抗体阻     

小肠移植急性排斥反应期移植肠白细胞介素2受体和细胞间粘？…

目的 探讨移植肠白细胞介素２受体（ＩＬ－２Ｒ）和细胞间粘附分子１（ＩＣＭＡ－１）的表达在小肠移植排斥反应中的意义及诊断价值．方法 选用近交系大鼠Ｆ３４４／Ｎ和Ｗｉｓｔａｒ／Ａ进行全小肠异位移植,实验分４组,第１组：Ｗｉｓｔａｒ;第２组：Ｗｉｓｔａｒ→Ｗｉｓｔａｒ;第３组：Ｆ３４４→Ｗｉｓｔａｒ;第４组：Ｆ３４４→Ｗｉｓｔａｒ＋环孢霉素Ａ（６ｍｇ·ｋｇ＾－１·ｄ＾－１）。术后第３、５、７天取各组动物     

大鼠移植小肠急性排斥反应期组织病理学研究

目的　探讨大鼠异位小肠移植急性排斥反应期移植小肠病理学特点及意义。方法　实验分 4组 ,每组 6只。A组为非手术对照组 ;B组为异系移植组 ;C组为同系移植组 ;D组为异系移植加环孢霉素A治疗组。术后 3 ,5 ,7,10d取移植小肠进行病理学检查 ,测量黏膜厚度 ,绒毛高度和隐窝深度 ;并检测 3 ,5 ,7d移植小肠黏膜细胞凋亡。结果　A组小肠黏膜正常 ;B组移植小肠炎性细胞浸润、黏膜结构破坏程度和黏膜细胞凋亡数目明显高于C ,D组 ,随移植时间的延长黏膜细胞凋亡数目增加 ,黏膜结构破坏程度加重 ;C组移植小肠黏膜结构损伤程度较B组轻 ;D组仅有少量炎性细胞浸润 ,间质轻度水肿 ,未见黏膜结构破坏。结论　炎性细胞浸润、黏膜细胞凋亡和黏膜结构破坏是移植小肠急性排斥反应损伤病理学变化的主要特点。动态观察移植小肠病理学变化和细胞凋亡 ,对诊断小肠移植急性排斥反应和估计损伤程度有一定的价值。     

肾移植急性排斥反应中肾小管上皮细胞凋亡的观察

目的 探讨肾移植急性排斥小以细胞凋亡与移植排斥的关系。方法 选用近交系ＤＡ大鼠,ＬＥＷ大鼠进行原位左肾移植。实验组：异基因移植组（ＤＡ－ＬＥＷ）,对照组;基因移植组（ＬＥＷ→ＬＥＷ）。于手术后第２、４、６天分别取移植肾进行病理学检查及电镜扫描,采用ＴｄＴ介导的脱氧核苷酸原位末端标记法（ＴＵＮＥＬ）检测移植肾脏中的凋主血清肌酐水平。结果 病理学检查结果显示实验组大鼠在术后第２、４、６天分别发生轻、中     

肾移植急性排斥反应中Fas-L表达与肾小管上皮细胞凋亡的研究

目的 探讨异基大鼠肾移植急性排斥期肾小管上皮细胞凋亡与Ｆａｓ－Ｌ表达的变化。方法 选用近交系ＤＡ（ＲＴ１＾ａ）、ＬＥＷ（ＲＴ１＾ｌ）大鼠进行原位左肾移植。实验组：异基因移植组（ＤＡ→ＬＥＷ）;对照组：同基因移植组（ＬＥＷ→ＬＥＷ）。于手术后第２、４、６天分别取移植肾进行病理学检查及电镜扫描,采用末端脱氧核苷酸转移酶（ＴｄＴ）介导的脱氧核苷酸原位末端标记法（ＴＵＮＥＬ）检测移植肾脏中的凋亡细胞,逆转     

大鼠小肠移植早期排斥反应中肠黏膜细胞凋亡与IL-1β的关系研究

目的明确小肠移植排斥反应中的细胞凋亡现象,并探讨白细胞介素1β(IL1β)在凋亡中的作用。方法选用SD/Wistar大鼠进行节段性小肠移植。实验分3组:同基因移植组(SD→SD);异基因移植组(Wistar→SD)和异基因移植加环孢素A治疗组(Wistar→SD+CsA)。术后第1,3,5,7天分别用TUNEL法检查移植肠上皮凋亡细胞,用ELISA法测定血清IL1β。结果TUNEL法显示:Wistar→SD组肠黏膜上皮细胞在其发生轻、中、重度排斥反应中存在细胞凋亡,凋亡细胞数随排斥反应的加重而增加(P<0.01),并显著高于SD→SD组(P<0.01)。Wistar→SD+CsA组细胞凋亡数亦有显著增加(P<0.01)。SD→SD组排斥反应轻微,凋亡细胞数无明显变化(P>0.05)。ELISA法显示:在SDSD组血清IL1β无明显变化(P>0.05),WistarSD组和Wister→SD+CsAz组随凋亡细胞数的增加血清IL1β亦增高(P<0.01)。IL1β增加与细胞凋亡指数增加呈正相关(r=0.798,P<0.01)。结论小肠移植排斥反应中存在细胞凋亡现象,IL1β在细胞凋亡发生中起促进作用。     

肠移植早期黏膜地址素细胞黏附分子在大鼠移植小肠及其肠系膜淋巴结的表达

目的 探讨黏膜地址素细胞黏附分子（MAdCAM-1）在大鼠小肠移植早期移植肠及其肠系膜淋巴结中的表达及意义。方法 选用近交系F344／N和BN大鼠建立全小肠异位移植模型后分3组：第1组，非手术对照组（F344／N）；第2组，同基因移植组（F344／N→F344／N）；第3组，异基因移植组（BN→F344/N）。术后1、3、5、7d取各组移植肠及其肠系膜淋巴结检测MAdCAM-1表达的分布及变化，同期进行移植肠组织病理学检查。结果 同基因移植组各检测时点的肠黏膜组织表现与正常小肠的组织学特征基本相同；异基因移植组肠黏膜组织表现符合轻-中-重度排斥反应的渐进过程，2周后移植肠绒毛变的低平，散在黏膜上皮脱落，移植肠相关肠系膜淋巴结萎缩明显。MAdCAM-1在急性排斥反应期，高表达于移植肠固有层及其肠系膜淋巴结，特别是高表达于肠黏膜固有层中的扁平血管内皮细胞表面。同基因移植组术后MAdCAM-1的表达在1—7d均无明显量的变化；而异基因移植组MAdCAM-1在移植肠中的表达呈上升趋势，而在其肠系膜淋巴结中的表达呈下降趋势。结论 MAdCAM-1与小肠移植急性排斥反应的进展关系密切。     

TGF-β1修饰的未成熟树突状细胞对大鼠移植小肠细胞凋亡的影响

目的 探讨经TGF-β1修饰的未成熟树突状细胞(imDC)预处理大鼠小肠移植受体后移植肠细胞凋亡的变化及意义.方法 选用近交系F344/N和BN大鼠建立全小肠异位移植模型,分4组,每组24只.A组:同基因移植组(BN→BN);B组:异基因移植组(F344/N→BN);C组:F344/N→BN异基因移植+TGF-β1基因转染imDC;D组:F344/N→BN异基因移植+TGF-β1基因转染imDC+FK506.术后3、5、7 d各处死6只,取出移植肠.行免疫组化检测Bcl-2和Bax表达,TUNEL及电镜观察细胞凋亡.同期进行移植肠组织病理学检查.结果 C组中Bcl-2在术后有轻度下降,而Bax的表达则略有升高,但明显低于B组,差异有统计学意义(P＜0.05);D组术后Bcl-2及Bax的表达与A组无明显差异.C组的凋亡细胞数在术后逐渐增加,但数量始终较少,与B组比较差异有统计学意义(P＜0.05);D组仅见少量凋亡细胞.结论 经TGF-β1基因转染的imDC预处理受体可以抑制细胞凋亡,从而减轻小肠移植术后急性排斥反应的程度.     

雷帕霉素和中药百令胶囊对大鼠小肠移植后细胞凋亡和FasL mRNA表达作用

目的：观察雷帕霉素（RAPA）和中药百令胶囊对大鼠小肠移植后细胞凋亡和凋亡基因FasL表达的作用。方法：以SD大鼠为假移植组作对照（1组），采用Wistar→SD大鼠异位小肠移植模型根据不同处理分为排斥组、RAPA2mg/kg和RAPA4mg/kg组以主RAPA2mg/kg加百令胶囊组，术后1、3、5、7d每组各取6只动物处死，获取移植肠组织进行病理学检查。取冰冻移植小肠标本行细胞凋亡的检测，采用QRT-PCR方法检测移植小肠村本FasLmRNA表达的情况。结果：排斥反应肆生时出现大量的肠上皮细胞凋亡，RAPA4mg/kg可显著地抑制肠细胞凋亡的发生，因2mg/kg与中药百令胶囊1mg/kg联合应用于术后7d抑的制凋亡的能力与RAPA4g/kg组无显著性差异。结论：细胞凋亡是诊断小肠移植排斥反应的一个良好的指示剂，RAPA4mg/kg可显著抑制细胞凋亡及凋亡基因FasLmRNA的表达，RAPA2mg/kg加百令胶囊虽有显著抑制细胞凋亡，但对FasLmRNA的表达无抑制作用。RAPA2mg/kg加百令胶囊联合应用对于抑制大鼠小肠移植排斥反应，抑制细胞凋亡是有相加或协同作用。     

p38蛋白激酶在小肠移植后肠黏膜上皮细胞凋亡机理中的作用

目的 探讨p38蛋白激酶（p38 MAPK）在小肠移植早期排斥反应中肠黏膜上皮细胞凋亡机理中的作用。方法 选用近交系SD和Wistar大鼠进行节段性小肠移植，实验分3组：同基因移植组（Wistar→Wistar组）、异基因移植组（SD→Wistar组）和异基因移植加环孢素A组（SD→Wistar＋CsA组）。分别于移植术后1、3、5及7d采集移植肠管行病理学检查排斥反应，TUNEL法检测凋亡细胞，并行Western—blotting测定p38MAPK表达；同时，ELIsA法测定血清TNF—α活性。结果 SD→Wistar组肠黏膜上皮细胞发生轻、中、重度排斥反应中存在细胞凋亡，凋亡细胞数随排斥反应的加重而增加（P〈0．01）；Wistar→Wistar组排斥反应轻微，凋亡细胞数无明显变化（P〉0．05）；SD→Wistar＋CsA组随着CsA的应用，排斥反应逐渐得到控制，且凋亡细胞数也随着减少。SD→Wistar组及sD→Wistar＋CsA组的血清TNF-α随移植肠管上皮细胞凋亡的轻重而发生相应的变化（P〈0．01）。p38 MAPK在SD→Wistar组随凋亡细胞数增加而表达加强（P〈0．01），Wistar→Wistar组p38 MAPK表达无明显变化（P〉0．05），在SD→wistar＋CsA组随凋亡细胞数而发生相应的变化（P〈0．01）。小肠移植早期排斥反应中肠黏膜上皮细胞凋亡现象与p38MAPK呈正相关（r=0．875，P〈0．01），血清TNF-α与移植肠上皮细胞凋亡呈正相关（r=0．837，P〈0．01），血清TNF-α与p38 MAPK亦呈正相关（r=0．826，P〈0．01）。结论 大鼠小肠移植排斥反应中存在肠黏膜上皮细胞凋亡现象，p38 MAPK参与细胞凋亡信号转导过程并起重要作用。     

脾肠联合移植对大鼠小肠移植免疫耐受的影响

目的　探讨脾肠联合移植对小肠移植免疫耐受的诱导作用。方法　选用SD大鼠为供体、Wistar大鼠为受体 ,进行异位全小肠和脾脏联合移植。实验分 3组 ,每组 6只。A组 :小肠移植非免疫干预组 ;B组 :受体脾切除 ,脾肠联合移植组 ;C组 :小肠移植环孢霉素A(CsA)治疗组。术后 3、5、7、10d取移植小肠回肠段 0 .5～ 1.0cm进行病理学检查 ,用病理图像分析系统测量黏膜厚度 ,绒毛高度和隐窝深度。采用TdT介导的脱氧核苷酸原位末端标记法 (TUNEL)检测 3、5、7d移植小肠黏膜细胞凋亡 ,评价移植小肠急性排斥反应损伤程度。结果　A、B两组均有不同程度的急性排斥反应损伤 ,但A组高于B组 ,移植后 3、5、7d分别属于轻、中、重度排斥 ,10d黏膜基本完全脱落。B组移植后 3、5d符合轻度排斥 ,7d中度以下排斥 4只 ,重度排斥 2只 ,10d中度排斥 2只 ,重度 4只 ,但仍可见黏膜层。C组移植后 10d 1只出现轻度排斥其余未见明显损伤。黏膜厚度、绒毛高度和隐窝深度B组明显高于A组 ,黏膜上皮细胞凋亡数目较A组低。结论　受体脾切除 ,脾肠联合移植可减轻移植小肠急性排斥反应损伤 ,诱导一定程度的小肠移植免疫耐受     

小肠移植急性排斥反应中bcl-2及bax表达的意义

目的探讨bcl-2及bax的异常表达与小肠移植急性排斥反应的关系。方法选用近交系F344/N和封闭群Wistar/A大鼠建立同种异基因小肠移植模型,并随机分为同基因移植组、异基因移植组、异基因加普乐可复(FK506)治疗组和对照组,用免疫组织化学技术检测36只大鼠术后移植肠组织中bcl-2及bax在移植肠组织中的表达。结果异基因组术后第3天,bcl-2的表达显著低于对照组(P<0.05),并随着移植天数的增加,差异更加具有显著性意义(P<0.01);bax的表达与对照组比较差异无显著性意义(P>0.05);FK506治疗组bcl-2及bax表达与对照组比较,差异均无显著性意义(P>0.05)。结论移植肠组织内bcl-2表达水平可作为早期诊断急性排斥反应的一个有参考意义的指标。     

Characterization of allograft rejection in an experimental model of small intestinal transplantation

Graft rejection continues to be a major barrier to the success of clinical small intestinal transplantation. The objective of this study was to characterize histopathologic and immune parameters of allograft rejection in an experimental model of small intestinal transplantation. Heterotopic intestinal transplants were performed in allogeneic and isogeneic rat strain combinations. An additional group of allogeneic recipients was treated with tacrolimus (1 mg/kg/day) for 7 days beginning on posttransplant day 1. Recipients of allografts and isografts were killed on days 1 to 7 following transplantation, and tacrolimustreated allograft recipients were killed on days 4 and 7. Grafts and native intestines were examined for histopathology and cytokine gene expression. Very early rejection was observed on posttransplant day 3 and severe rejection was apparent by day 7. The key histopathologic features of acute graft rejection including apoptosis, crypt epithelial cell injury, and an inflammatory infiltrate were uniformly identifiable on day 4 and progressed in severity through day 7. Interleukin (IL)-2, IL-4, IL-5, IL-6, interferon-γ (IFN-γ), and tumor necrosis factor-γ mRNA were readily detectable in allografts on days 1 to 7. However, only IFN-γmRNA showed a significant early and sustained increase in allografts as compared to isografts and native intestine. Treatment of allograft recipients with tacrolimus abrogated the major histopathologic features of rejection and markedly inhibited IFN-γgene expression. These results indicate that graft rejection in small intestinal transplantation is characterized by a local and specific immune response marked by WN-γproduction that results in crypt epithelial cell injury and apoptosis. Tacrolimus abrogates the histopathologic features of rejection in association with a marked inhibition of IFN-γgene expression. Supported by grants from the Lucile Packard Foundation and the Office of Technology and Licensing, Stanford University     

大鼠移植心脏的细胞凋亡及其与急性排斥反应的关系

目的 观察移植心脏的细胞凋亡现象及其与急性排斥反应的关系。方法 建立大鼠异位心脏移植模型,用ＨＥ梁色和原位末端标记（ＴＵＮＥＬ）技术检测移植心脏切片,进行排斥反应的病理分级,计算凋亡指数（ＡＩ）。结果 发生凋亡的细胞主要是心肌细胞,在各级排斥反应中均可见凋亡细胞存在,且ＡＩ与急性排斥发生的分级成正相关;各级的ＡＩ与０级（无排斥反应）比较,差异均有显著性。结论 细胞凋亡与移植心脏急性排斥反应的严重程     

Intestinal tight junction in allograft after small bowel transplantation

INTRODUCTION: In the intestinal physical barrier, tight junctions between intestinal epithelial cells play a central role. There is increasing evidence that rejection after small bowel transplantation promotes intestinal barrier injury to allografts. Our aim was to study the morphological changes of tight junctions in allografts during rejection. METHODS: Small bowel transplantation was performed using the F344 to Lewis rat model. Animals were divided into three groups: isogeneic controls, acute rejection group, and chronic rejection group. Allograft rejection was characterized by hemotoxylin and eosin staining of mucosal tissue sections. Tight junctions in grafts were investigated by transmission electron microscopy. RESULTS: Acutely rejected allografts showed severe mucosal injury and completely loosened tight junctions, while chronically rejected allografts revealed less mucosal injury and remained with partial integrity of their tight junctions. CONCLUSION: Our study demonstrated for the first time the morphological alterations of tight junctions in allograft mucosa during acute and chronic rejections, suggesting disruption of tight junctions was relative to the intestinal inflammatory processes.     

Host immune suppression after small bowel/liver transplantation in rats

Simultaneous liver grafting in the Lewis (RT1¹)-to-DA (RT1^a) rat strain combination protects small intestinal grafts from rejection. The present study examined host immune responses after combined small bowel/liver transplantation (SBL) in this model. Orthotopic liver transplantation and heterotopic small intestinal transplantation were performed simultaneously and compared with isolated small bowel allografts (SBA) and isolated small bowel isografts (SBI). All rats were sacrificed on postoperative day (POD) 7 or 14 for immunological and histological studies. The mean time to rejection of the SBA was 6.6±0.3 days. Incontrast, there was no clinical or histological evidence of intestinal rejection in SBL recipients during the 14 days of follow-up. The SBL recipients showed clinical and histological evidence of graft-versushost disease (GVHD). Lmphocyte proliferation and IL-2 production in response to donor antigens were suppressed after SBL transplantation compared with the SBA or the SBI controls (P<0.05). Cell-mediated cytotoxicity and lymphocytotoxic antibody production against donor cells were also significantly inhibited in the SBL recipients compared with the SBA control group (P<0.05). We conclude that SBL transplantation in the Lewis-toDA rat strain combination: (1) suppresses host alloimmune responses, (2) prevents early intestinal rejection, and (3) favors the development of GVHD.     

烧伤早期家兔小肠细胞凋亡的研究

目的　探讨严重烧伤早期家兔小肠粘膜上皮细胞、淋巴细胞以及蚓状突淋巴细胞凋亡及其意义。　方法　采用日本大耳白兔 2 5只 ,随机分成 5组 :正常对照组、严重烧伤 3、6、12、2 4h组 ,每组均为 5只。各烧伤组制作成 30 %TBSAⅢ度烧伤动物模型 ,于伤后相应时相点对 5个部位的肠组织取材 ,行HE染色、电镜检查及用DNA切口末端标记技术 (TUNEL)行原位细胞凋亡检测 ,TUNEL切片作统计分析。　结果　HE染色烧伤组见较多凋亡细胞单个分散在小肠及蚓状突粘膜上皮层、粘膜固有层 (部分延伸到粘膜下层 )的淋巴小结和散在淋巴组织中 ;伤后 2 4h组有少数肠粘膜断裂 ;所有切片未见明显炎症及坏死现象。电镜显示凋亡小体形成。TUNEL法见大量呈蓝黑色的阳性细胞核 ,分布位置同HE染色。伤后 3h小肠及蚓状突细胞凋亡数较对照组已有明显增多 (P<0 .0 1) ,到 6和 12h显著升高达峰值 (P <0 .0 1) ,伤后 2 4h已下降接近 3h水平 ,但仍高于对照组 (P <0 .0 1) ;烧伤组家兔中段及远端小肠粘膜上皮细胞凋亡数均高于近端小肠 (P <0 .0 5 )。　结论　严重烧伤早期家兔小肠粘膜上皮细胞、淋巴细胞以及蚓状突淋巴细胞大量凋亡 ,中远端小肠粘膜上皮细胞凋亡较近端小肠显著 ,这些变化可能是烧伤后肠道细菌及内毒素移位的细胞学基础。     

血小板源性生长因子A在大鼠移植心脏血管病变及纤维化中的作用

目的 探讨血小板源性生长因子A(PDGF-A)在移植心脏血管病变及心肌纤维化中的作用.方法 选择近交系健康雄性Wistar大鼠及SD大鼠,建立大鼠异位心脏移植模型.实验分为四组,每组8只.正常对照组:取正常Wistar大鼠的心脏作为空白对照.无排斥组:心脏移植的供、受者均为Wistar大鼠,移植后第60天取移植心脏.急性排斥组和慢性排斥组:心脏移植的供者均为Wistar大鼠,受者均为SD大鼠;急性排斥组术后未行免疫抑制治疗,术后第5天取移植心脏;慢性排斥组术后给予环孢素A 10 mg·kg-1·d-1,皮下注射,移植后第60天取移植心脏.采用免疫组织化学染色法检测移植心脏的巨噬细胞浸润(CD68阳性细胞数)情况;逆转录聚合酶链反应(RT-PCR)分析PDGF-A mRNA的表达水平.结果 正常对照组和无排斥组未见巨噬细胞浸润;急性排斥组巨噬细胞浸润主要见于心肌及冠状血管周围;慢性排斥组巨噬细胞浸润见于心肌及血管周围,在心肌坏死纤维化较严重的区域,巨噬细胞浸润尤为明显;正常对照组、无排斥组、急性排斥组和慢性排斥组移植心组织中PDGF-A mRNA的相对表达量分别为:0.26±0.06、0.31±0.04、0.88±0.12和0.94±0.11,慢性排斥组和急性排斥组中PDGF-A mRNA的相对表达量明显高于正常对照组和无排斥组(P＜0.01).结论 巨噬细胞浸润及血小板源性生长因子表达水平与移植心脏血管病变及心肌纤维化有关.     

Apoptosis and functional changes of dipeptide transporter (PepT1) in the rat small intestine after traumatic brain injury

BACKGROUND: Traumatic brain injury (TBI) can induce significant alterations of intestinal mucosal structure and barrier function. However, it has not been investigated whether, and to what degree, apoptosis and alterations of absorptive function in the intestinal mucosal epithelium occur after TBI. MATERIAL AND METHODS: Male Wistar rats were randomly divided into seven groups (five rats each group) including normal group, control group with sham operation, and TBI groups at hours 3, 12, 24, and 72, and on day 7. Parietal brain contusion was adopted using weight-dropping method. Intestinal mucosal structure was examined using histomorphmetric study and electron microscopy, and apoptosis was detected by TUNEL method. An everted sleeve of intestine was securely incubated in Kreb's solution with radioactive dipeptide ((3)H-Gly-Sar, 10 microCi/mL) to measure the uptake and transport of PepT1 of small intestinal epithelial cells. RESULTS: The villous height, crypt depth and surface area were significantly decreased at 24 h after TBI, and further declined to the degree of mucosal atrophy on day 7 after TBI. Apoptotic changes of condensed nuclei in epithelial cells and fractured, distorted, and sparse microvilli were found by electron microscopy. The number of apoptotic cells in the mucosal epithelium was significantly increased since 3 h after TBI, peaked at 72 h post-injury, then declined at 7 days, but was still higher than that of control. There was a highly negative relation between the apoptotic index and the villous height, the crypt depth, and villous surface area. Compared with that of normal and control rats, the transport and uptake of dipeptide was significantly increased at 3 h post-injury (P < 0.01), peaked at 12 h and declined a bit at 24 h post-injury, and returned to the level of normal and control rats at 72 h and 7 days. CONCLUSIONS: It is highly suggested that intestinal mucosa apoptosis plays an important role in the pathogenesis of acute gut damage after TBI. Intestinal PepT1 expression could be up-regulated after traumatic brain injury, and maintained the normal level under the condition of serious intestinal damage. Up-regulation of PepT1 may adaptively improve absorption of di- and tripeptides, independent of changes in the mucosal surface area.