大鼠创伤性脑损伤后肠黏膜屏障的应激性变化

目的探讨创伤性脑损伤后大鼠肠黏膜屏障的应激性变化及其发生的形态学基础。方法雄性Wistar大鼠64只,均分为创伤性脑损伤组和假手术对照组,再分别按术后6、12、24和48 h时相点分为4个亚组(n=8);偶氮显色法鲎实验定量测定门静脉血内毒素水平;荧光显微镜检测肠系膜淋巴结、肝、脾、胰、肺和肾组织匀浆中标记的大肠杆菌移位率;观察肠黏膜组织病理及扫描和透射电镜下超微结构的变化。数据采用t检验。结果损伤后6 h,脑损伤但大鼠内毒素水平即开始升高,为(0.382±0.014)Eu/ml,12 h为(0.466±0.018)Eu/ml,24 h达高峰,至(0.478±0.029)Eu/ml,此后回落, 48 h为(0.412±0.036)Eu/ml,仍未降至正常,与对照组各时相点内毒素水平(0.102±0.007、0.114±0.021、0.112±0.018、0.108±0.011)比较,差异有统计学意义(P值均<0.05);多脏器荧光标记检出大肠杆菌的大鼠数均比对照组明显升高(P<0.05);光学显微镜下脑损伤组大鼠肠黏膜上皮细胞受损;透射电镜下可见细胞间紧密连接较对照组增宽。结论大鼠创伤性脑损伤后早期肠黏膜屏障功能即受损,肠黏膜通透性增高,细胞间紧密连接增宽可能是其形态学基础。     

脑外伤大鼠肠运动功能障碍及与血清Ghrelin的关系

目的探讨创伤性脑损伤（TBI）后大鼠肠运动功能异常及其与血清Ghrelin改变的关系。方法雄性Wistar大鼠64只,随机分为两组。TBI组采用改良Feeney自由落体撞击伤法建立TBI模型;对照组只开骨窗,不行落体致伤。两组大鼠分别在致伤后3、6、12、24 h观察血清Ghrelin水平、小肠传输系数及肠黏膜病理改变。结果 TBI后各组大鼠光镜下肠黏膜上皮细胞明显受损,电镜下可见细胞连接较对照组增宽;各时间点的肠道传输系数及血清Ghrelin值均低于对照组,二者呈正相关。结论大鼠在TBI后早期即可出现小肠黏膜损伤和小肠运动功能减低,在此期间血清Ghrelin的变化可能起一定作用。     

早期细胞凋亡在创伤性脑损伤肠黏膜屏障应激性变化中的作用

目的 探讨早期细胞凋亡在创伤性脑损伤(TBI)大鼠肠黏膜屏障应激性变化中的作用.方法 选用雄性Wistar大鼠64只,随机分为TBI组(32只)和假手术对照组(32只).2组大鼠分别按术后6、12、24和48 h时相点分为4个亚组(每个亚组8只).在光镜和透射电镜下观察肠黏膜组织形态学变化,同时用Annexin Ⅴ-PI双染法经流式细胞仪检测各组早期细胞凋亡率.结果 光镜下TBI组可见肠黏膜上皮细胞受损,电镜下可见其细胞间紧密连接较假手术对照组增宽,并可见典型的凋亡细胞.TBI组的创伤后早期即可见肠黏膜细胞的凋亡率较假手术对照组明显升高[6 h:(13.5±3.7)%比(6.1±1.7)%,P＜0.05;12 h:(66.1±6.0)%比(5.2±1.1)%,P＜0.05;24 h:(39.8±4.8)%比(8.4±2.6)%,P＜0.05;48 h:(7.5±1.3)%比(6.6±0.5)%].结论 大鼠TBI后的早期,肠黏膜屏障功能即可受损,肠黏膜上皮细胞早期凋亡率的增加可能在这一病理生理过程中起着重要作用.     

诱导型一氧化氮合酶在创伤性脑损伤后肠黏膜屏障损伤中表达的变化

目的观察创伤性脑损伤（TBI）后肠黏膜屏障损伤时诱导型一氧化氮合酶（iNOS）表达的变化及其可能的作用。方法 48只健康雄性W istar大鼠随机分为TBI组（n=24）和对照组（n=24）,各组动物分别在手术后3、6、12、24 h处死,每个时间点6只。动物处死后,抽门静脉血测血清内毒素、二胺氧化酶（DAO）,取脑组织和回肠黏膜,观察组织形态学改变,并测定肠黏膜组织DAO的含量和iNOS的表达情况。结果 TBI组肠黏膜受损,血中内毒素含量增加（P〈0.05）;肠黏膜DAO活性下降（P〈0.01）,而血中DAO活性则升高（P〈0.05）;iNOS的表达3h已经增高,12h达到最高,而后逐渐降低,但仍然高于对照组（P〈0.05）。结论 iNOS在TBI后肠黏膜屏障损伤时表达明显增加,参与了TBI后肠黏膜屏障损伤。     

重症急性胰腺炎大鼠并发肠黏膜屏障功能障碍

目的探讨重症急性胰腺炎(SAP)大鼠肠黏膜屏障功能的状况。方法 48只SD大鼠,随机分两组:假手术组(A组,n=24)、SAP模型组(B组,n=24)。用3%牛磺胆酸钠制备SAP大鼠模型。麻醉苏醒,即开始灌胃,6h/次,A、B组用灌胃器按1 mL/100 g/次生理盐水灌胃。制模后各组在6、12、24 h 3个时间点取材;开腹后观察腹水量及其颜色,观察胃肠道大体情况;取血用酶联免疫吸附双抗夹心法检测血清二胺氧化酶(DAO)及D-乳酸浓度;取胰腺及回肠末段组织做病理检查,并进行胰腺病理组织评分;取回肠末段部分组织做扫描电镜检查。结果A组无腹水;B组腹水多,肠道明显扩张,积液积气,部分肠管发黑。B组血清DAO、D-乳酸的浓度较A组升高(P<0.01)。B组胰腺及回肠病理损害重,胰腺病理组织评分较A组高(P<0.05);扫描电镜检查A组基本正常,B组损伤重。结论 SAP大鼠并发肠黏膜屏障功能障碍。     

氧自由基在弥漫性脑损伤大鼠应激性肠黏膜损伤发生中的作用

2002年6月至2004年6月,我们采用光镜观察了重度弥漫性脑损伤大鼠肠黏膜的形态学改变,并动态观察了不同时相大鼠肠组织匀浆中氧自由基相关指标黄嘌呤氧化酶(XO)、髓过氧化酶(MPO)、丙二醛(MDA)、二胺氧化酶(DAO)的改变,旨在探讨氧自由基在应激性肠黏膜损伤发生中的作用,为临床重度颅脑损伤后早期肠黏膜屏障的保护及肠道营养的应用提供理论依据。     

G-CSF对创伤性脑损伤大鼠神经再生作用的研究

目的探讨应用粒细胞集落刺激因子（G—CSF）治疗对44伤性脑损伤（TBI）大鼠模型神经功能恢复及神经细胞再生的作用。方法将60只健康雄性Wistar大鼠随机分成假手术对照组、脑创伤对照组、G—CSF治疗组。采用Feeney法制备中度脑创伤模型,O—CSF治疗组在大鼠脑创伤后立即给予G—CSF50μg／（kg·d）,两对照组给予等量的生理盐水,连续3d。通过BrdU标记新生增殖细胞,于术后1d、4d、7d、14d对各组大鼠进行神经功能缺失评分（mNSS）,并取大鼠脑组织行HE染色观察脑组织病理改变,免疫组织化学荧光法进行BrdU染色、BrdU／NeuN双染色检测新生增殖细胞及其分化方向。结果G—CSF治疗组4d、7d、14d时mNSS评分明显低于脑创伤对照组（P〈0．05）,高于假手术对照组（P〈0．05）。BrdU阳性细胞数在用药后4d、7d、14d时G—CSF治疗组明显高于40伤对照组、假手术对照组（P〈0．05）,并且于7d时达高峰;对比7d时创伤周围脑组织BrdU／NeuN双阳性细胞数,O—CSF治疗组明显高于脑创伤对照纽、假手术对照组（P〈0．05）,脑创伤对照纽、假手术对照组相比差异有统计学意义（P〈0．05）。结论应用G～CSF治疗TBI大鼠能明显促进大鼠神经功能恢复,增加创伤周围脑组织细胞增殖,并向神经元细胞方向分化。     

肠易激综合征患者小肠黏膜5-HT信号系统的研究

目的探讨肠易激综合征（IBS）患者不同部位小肠黏膜5-羟色胺（5-HT）水平及肠嗜铬细胞（EC细胞）数量是否改变。方法选取24例便秘型IBS（IBS-C）、26例腹泻型IBS（IBS-D）患者和26名健康人,行小肠镜及结肠镜检查并取十二指肠降段、近端空肠和回肠末段黏膜,用高压液相色谱-电化学法和免疫组织化学检测5-HT含量和EC细胞。结果IBSC患者近端空肠黏膜的5-HT含量与健康人相比有统计学意义（122±54ng／mg蛋白比188±91ng／mg蛋白,P〈0．05）,而十二指肠降段和回肠末段黏膜5-HT含量（182±90ng／mg蛋白、61±35ng／mg蛋白）与健康人相比（256±84ng／mg蛋白、93±45ng／mg蛋白）无统计学意义（P〉0．05）。IBS-D患者不同部位小肠黏膜5-HT含量与健康人相比均无统计学意义（P〉0．05）。IBS-C和IBSD患者不同部位小肠黏膜EC细胞数量与健康人相比均无统计学意义（P〉0．05）。结论上述结果提示1BS患者小肠黏膜5HT信号系统异常是其发病机制之-,但是在IBS-C和IBS-D之间有差异。     

肝衰竭与肠屏障功能障碍关系的研究进展

肝衰竭是指由多种因素引起的严重肝脏损害,导致肝脏本身合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,临床上出现以凝血机制障碍、黄疸、肝性脑病、腹水等为主要表现的一组症候群.肠屏障功能障碍引起肠源性内毒素血症在肝衰竭的发病中起着重要作用,是引起肝功能衰竭患者病情恶化和死亡的重要原因.因此,对肠屏障功能障碍的早期诊断并采取有效的防治措施显得极其重要.但是,由于肠道功能的复杂性及缺乏明确的功能监测指标,对于肠屏障功能障碍的发生机制、诊治等问题尚缺乏一致意见.现将目前关于肝衰竭与肠屏障功能障碍之间关系的研究进展综述如下.     

肠易激综合征患者小肠运动功能的研究

肠易激综合征(IBS)是临床上最常见的功能性肠病,其病因及发病机制仍不清楚,可能与精神心理异常、内脏感觉异常、胃肠动力紊乱及肠道感染等因素有关。有关IBS结肠动力异常的研究较多,但IBS与小肠运动功能相关关系的研究国内尚少见报道。本研究观察IBS患者小肠消化间期移行性复合运动(MMC)及胃肠通过时间的变化,客观评价IBS     

Effects of intestinal mucosal blood flow and motility on intestinal mucosa

AIM:To investigate the role of intestinal mucosal blood flow(IMBF) and motility in the damage of intestinal mucosal barrier in rats with traumatic brain injury.METHODS:Sixty-four healthy male Wistar rats were divided randomly into two groups:traumatic brain injury(TBI) group(n = 32),rats with traumatic brain injury;and control group(n = 32),rats with sham-operation.Each group was divided into four subgroups(n = 8) as 6,12,24 and 48 h after operation.Intestinal motility was measured by the propulsion ratio o...     

Effects of psychological stress on small intestinal motility and bacteria and mucosa in mice

AIM: To investigate the effects of psychological stress on small intestinal motility and bacteria and mucosa in mice, and to explore the relationship between small intestinal dysfunction and small intestinal motility and bacteria and mucosa under psychological stress. METHODS: Sixty mice were randomly divided into psychological stress group and control group. Each group were subdivided into small intestinal motility group (n= 10), bacteria group (n = 10), and D-xylose administered to stomach group (n= 10). An animal model with psychological stress was established housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (Escherichia coli) and anaerobes (Lactobacilli). The quantitation of bacteria was expressed as Iog10(colony forming units/g). D-xylose levels in plasma were measured for estimating trie damage of small intestinal mucosa. RESULTS: Small intestinal transit was inhibited (39.80±9.50% vs 58.79±11.47%,P<0.01) in mice after psychological stress, compared with the controls. Psychological stress resulted in quantitative alterations in the aerobes (E.coli). There was an increase in the number of E coli in the proximal small intestinal flora (1.78±0.30 log10(CFU/g) vs 1.37±0.21 log10(CFU/g), P<0.01), and there was decrease in relative proportion of Lactobacilli and E.coli of stressed mice (0.53±0.63 vs 1.14±1.07,P<0.05), while there was no significant difference in the anaerobes (Lactobacilli) between the two groups (2.31±0.70 log10 (CFU/g) vs 2.44±0.37 log10(CFU/g), P>0.05). D-xylose concentrations in plasma in psychological stress mice were significantly higher than those in the control group (2.90±0.89 mmol/L vs 0.97±0.33 mmol/L, P<0.01). CONCLUSION: Small intestinal dysfunction under psychological stress may be related to the small intestinal motility disorder and dysbacteriosis and the damage of mucosa probably caused by psychological stress.     

Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats

AIM： To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth （SIBO） in Nonalcoholic steatohepatitis （NASH）, and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied.
METHODS： Forty eight rats were randomly divided into NASH group （n = 16）, cidomycin group （n = 16） and control group （n = 16）. Then each group were subdivided into small intestinal motility group （n = 8）, bacteria group （n = 8） respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes （E. coli and anaerobes （Lactobacilli）. Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis.
RESULTS： Small intestinal transit was inhibited in NASH group （P 〈 0.01）. Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group （P 〈 0.01）. High fat diet resulted in quantitative alterations in the aerobes （E. coli） but not in the anoerobics （Lactobacill）. There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group （1.70 ± 0.12 log10 （CFU/g） vs 1.28 ± 0.07 log10 （CFU/g）, P 〈 0.01）. TNF-α concentration was significantly higher in NASH group than in control group （1.13 ± 0.15 mmol/L vs 0.57 ± 0.09 mmol/L, P 〈 0.01）. TNF-α concentration was lower in cidomycin group than in NASH group （0.63 ± 0.09 mmol/L vs 1.13 ± 0.15 mmol/L, P 〈 0.01）. Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-α levels of NASH rats.
CONCLUSION： SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can allevi     

大鼠创伤性脑损伤后认知行为的变化

目的 建立直接手术损伤大鼠部分脑皮质及海马CA1区的创伤性脑损伤模型,并观察损伤后动物认知行为的改变情况.方法 将大鼠进行脑损伤建模后,于术后11～15 d和26～30 d采用Morris水迷宫的方法评价动物的认知行为变化后,灌杀动物取脑切片,HE染色及尼氏染色观察损伤范围;胶质纤维酸性蛋白(GFAP)免疫组织化学染色观察星型胶质细胞(AST)的活化及胶质瘢痕形成情况;术后5 d行Nestin及GFAP双重免疫荧光染色显示海马内干细胞的激活,并观察损伤边缘的干细胞迁移情况.结果 直接手术损伤部分脑皮质及海马CA1区后,造成了动物认知功能障碍,并且1个月时有自发的认知功能恢复;5 d时星型胶质细胞活化,1个月时胶质瘢痕的形成.结论 本实验采用的模型可成功造成动物认知行为的改变,为组织工程材料的移植治疗脑损伤提供了比较适用的研究模型.     

丙氨酰—谷氨酰胺二肽对脑外伤大鼠心肌细胞的保护作用

目的探讨丙氨酰—谷氨酰胺二肽（Ala-Gln）对创伤性脑损伤（TBI）大鼠心肌细胞的保护作用。方法48只健康雄性Wister大鼠随机分为假手术对照组（A组）、TBI组（B组）和TBI后Ala-Gln干预组（C组）。各组大鼠均于伤后48 h处死取材,测定血清天门冬氨酸转氨酶（AST）和心肌型肌酸激酶同工酶（CK-MB）;测定心肌组织超氧化物歧化酶（SOD）和丙二醛（MDA）水平,并观察心肌病理学改变。结果与A组比较,B组大鼠48 h血清AST、CK-MB水平升高,心肌组织SOD减少、MDA增加,同时光镜下可观察到心肌组织水肿变性、炎细胞浸润和灶性坏死等改变;C组心肌细胞变性和坏死明显减轻,血清心肌酶及心肌组织SOD、MDA水平较B组有不同程度改善,并且呈明显的时效关系。结论TBI后可出现心肌损伤,应用Ala-Gln可有效减轻TBI引起的心肌损害,在创伤早期应用效果更显著。     

Adaptive changes in postprandial motility after intestinal resection and bypass

An electromyographic technique was used to study the changes in postprandial motility induced by jejunal and ileal resection and jejunal bypass (50% reduction of total length of small bowel). Electrodes were implanted in rats throughout the intestine. Compared to control animals, the duration of postprandial interruption of the myoelectric complex (DIMC) was rapidly increased after jejunal resection, more gradually augmented after jejunal bypass, and remained constant after ileal resection. The frequency of occurrence of spike bursts during the postprandial period was significantly decreased in the short remaining proximal segment after jejunal resection and was not changed in the ileum. The jejunal bypass induced no change in the frequency throughout the remaining bowel. Ileal resection was followed by a decrease on the jejunum. The percentage of slow waves superimposed by a spike burst remained constant after jejunal resection and bypass but was significantly decreased after ileal resection on the whole remaining intestine. These results show important modifications in postprandial motor activity of the small bowel, which appear rapidly after jejunal resection, more gradually after jejunal bypass, and which are less pronounced after ileal resection. This electromyographic study emphasizes the role of intestinal motility in the development of adaptation after small bowel resection or bypass.     

急性脑缺血后肠道血流灌注和动力的变化及其对肠黏膜屏障的影响

目的 探讨急性脑缺血后大鼠肠黏膜血流灌注和动力变化对肠黏膜屏障的影响. 方法雄性Wistar大鼠64只,随机分为急性脑缺血组(32只)和假手术对照组(32 只),两组大鼠分别按术后6、1 2、24和48 h时相点分为4个业组(每组均为8只),进行肠黏膜血流量、肠道传输系数、门静脉血内毒素水平以及多脏器组织匀浆中标记大肠杆菌移位率的检测. 结果 急性脑缺血组6、1 2、24和48 h时相点肠黏膜血流量分别为(34.5±3.2)PU、(22.7±1.9) PU、(26.2±4.3)PU和(30,5±4.1)PU,与对照组(46.8±5.4)PU、(50.1±3.6)PU、(45.4+4.1)PU、(48.7±7.3)PU比较,明显降低(t=2.650、2.875、2.639、2.507,均P＜0.05);肠道传输系数脑缺血组各时相点分别为0.59±0.07、0.48±0.06、0.50±0.08和0,57±0.04,均低于对照组0.73±0.04、0.75±0.02、0.74±0.06、0.76±0.03(t=2.409、2.758、2.649、2.807,均P＜0.05);脑缺血组损伤后6 h内毒素水平即开始升高,24h达到高峰.各时相点较对照组均明显升高(均P＜0.05).脑缺血组多脏器荧光标记大肠杆菌总检出率(11.4％、18.8％、25.0％、12.5％)明显高于对照组(2.1％、4.2％、2.1％、0％);内毒素水平与肠黏膜血流量和肠道传输系数呈显著相关性(r=-0.861、-0.7 96,均P＜0.05). 结论 急性脑缺血后早期肠黏膜通透性就已增高,而脑损伤大鼠肠黏膜血流、肠运动功能的下降是导致此病理生理变化的重要因素.