人工气管移植新进展

对于因广泛而严重的炎症或肿瘤引起的良恶性气管狭窄 ,有时需要切除一段病变气管 ,并行气管再建术。当切除气管的长度小于 4 .5～ 6cm时 ,可以直接行端 -端吻合 [1] ,但当缺损更长时 ,就必须行气管移植术。这方面的研究主要包括 ;1、自体组织重建 ;2、同种异体气管移植 ;3、人工气管移植。本文主要综述人工气管的移植。1　人工气管移植的概况Neville等 [2 ]认为理想的人工气管假体应具备 :1、密闭不漏气 ;2、有适当的坚硬度 ;3、不被受体排斥 ;4、炎症反应轻微 ,并能被周围组织固定 ;5、对成纤维细胞和管腔内的细菌无通透性 ;6、允许呼吸道…     

实验性犬气管照射与深低温保存后同种异体移植的研究

目的 探讨气管大剂量照射与深低温保存后同种异体节段性气管移植的可行性。方法 健康杂种狗22只，分两组：对照组供体气管不做任何处理。实验组供体气管照射100000cGy后液氮深低温（－196℃）保存，同种异体气管移植长度为4cm(5-6个环）。移植后两组动物均不使用免疫抑制剂。结果 对照组动物均于移植后2－3周因气管狭窄窒息死亡或处死，肉眼标本见移植段气管明显狭窄，挛缩，部分软骨脱落。照射与深低温保存组动物于移植后1个月内无狭窄症状，但半数动物于术后1．5－2个月出现不同程度的狭窄，其中3只动物气管内置管后临床症状缓解。半数实验组动物移植段气管无狭窄发生，内膜光滑，吻合端愈合良好，动物长期生存。结论 气管大剂量照射与深低温保存方法可降低同种异体移植的免疫原性，经此法处理的气管移植后可不使用免疫抑制剂，是一种值得继续探讨、有临床应用前景的方法。     

自体肺修补气管缺损的动物实验研究

目的 :用肺组织行胸内气管大面积缺损修补。方法 :14例实验犬的气管进行一侧壁切除形成气管壁的缺损 ,于缺损处放置与气管管型一致的金属网架做支撑。缺损处用带血运的肺组织进行修补 ,重建气管。结果 :3条术后 1周内死亡 ,11条存活 ,最长存活时间达 72周。存活犬的气管管腔可观察到新生纤毛柱状上皮 ,修补局部轻微增生。结论 :说明应用肺组织行胸内气管大面积缺损修补有可能是一种较为理想的新术式。     

芥子气致大鼠气管损伤的形态学研究

目的建立芥子气致大鼠呼吸道损伤的动物模型，观察芥子气损伤大鼠气管的组织和细胞形态学变化。方法雄性大鼠72只，随机分为芥子气组（n=32）、丙二醇对照组（n=32）和正常对照组（n=8）。芥子气组气管内注入稀释的芥子气（0．1ml，2mg／kg），光镜和电镜下观察气管组织和细胞形态学改变。结果芥子气组（6h、24h、48h、72h）光镜所见：气管黏膜上皮细胞部分脱落，灶性溃疡形成，纤毛紊乱，黏膜固有层腺体增多，黏膜下层大量炎细胞浸润。芥子气组（72h）电镜所见：杯状细胞细胞膜缺失，线粒体嵴模糊、髓样变；纤毛细胞、基底细胞、成纤维细胞细胞核膜不清，核固缩，染色质边集。丙二醇对照组气管组织和细胞结构与正常对照组相同。结论芥子气（2mg／kg）可致大鼠气管组织和细胞急性损伤，组织损伤以黏膜上皮细胞脱落、灶性溃疡形成、黏膜下炎细胞浸润为特征，损伤程度随时间延长而加重。细胞损伤表现为杯状细胞细胞膜和细胞器损伤，纤毛细胞、基底细胞、成纤维细胞细胞核染色质损伤。     

骨化性气管支气管病4例及文献复习

目的:总结骨化性气管支气管病(TO)的临床特点，减少临床误诊率及漏诊率。方法:收集我院诊治的4例TO患者的临床资料，并检索国内数据库，总结116例TO患者的临床特点。结果:116例TO中男性65例，女性51例。临床表现无特异性，以组合性呼吸道症状多见。支气管镜检查可见气管及支气管前壁及侧壁黏膜下多发质硬结节，突向管腔，后壁不易受累。组织病理活检可见黏膜下出现软骨或成熟骨组织。治疗上对症处理，出现严重管腔狭窄可采用内镜介入或外科手术。结论：TO是一种预后较好的良性疾病， 支气管镜及组织病理活检有特征性改变,可以确诊。     

小鼠气管异位移植后肺移植慢性排斥反应模型的建立

目的通过建立小鼠的气管异位移植模型来模拟肺移植慢性排斥反应,为国内的闭塞性细支气管炎研究提供一种新的模型选择。方法同种异体移植组（Allograft组）以BALB／c小鼠为供者,C57BL／6小鼠为受者,同系移植组（Isograft组）供受者均为BALB／c小鼠。取供体小鼠的气管、左右主支气管连续气道作为供体,异位移植到受体小鼠背部皮下。分别于移植后第5、14、28天时,各取3只,将移植气管段取出作组织学分析。结果18例模型动物全部存活,无感染。病理切片示Allograft组小鼠移植气管管腔闭塞,慢性炎细胞浸润广泛,气管上皮完全脱落,纤维组织增生明显,呈现闭塞性细支气管炎表现;Isograft组小鼠移植气管的组织形态未见明显异常。结论小鼠异位气管移植的动物模型简单、经济、稳定性强、重复性好,能准确复制肺移植后闭塞性细支气管炎的病理过程。     

尼龙圈结扎胃结肠壁全层安全性的初步实验研究

目的初步探讨尼龙圈结扎胃及结肠壁全层的安全性，为不断扩展的临床应用提供依据。方法成年狗4只，在纤维胃镜及开腹直视配合下应用尼龙圈结扎胃及结肠壁全层，术后3、7、10、17d分别行剖腹术观察结扎部位组织愈合情况。结果所有动物术后恢复良好，观察期间无感染及出血征象。剖腹检查未发现胃结肠穿孔，无局部脓肿形成。结扎部位可见溃疡样缺损。组织学检查可见胃结肠壁肌层断裂，肉芽组织连接胃结肠缺损部位，并逐渐转化为瘢痕组织。术后17d可见再生黏膜完全覆盖缺损表面。结论尼龙圈结扎胃结肠壁全层具有一定安全性，可进一步拓宽尼龙圈结扎在临床中的应用。     

T-1型脱细胞异体组织补片在口腔颌面外科的临床应用

各种原因引起的口腔黏膜缺损的修复，临床一般采取自体组织移植法，这种传统的方法在治疗口腔颌面部皮肤黏膜组织病损中发挥了一定的作用，但又有难以克服的弊病。近年来人工真皮的研究进展迅速，尤其是脱细胞异体真皮基质已经在烧伤和整形领域中皮肤移植的成功应用。脱细胞异体组织补片是应用组织工程学技术，将异体组织经过脱细胞处理后，去除引起异体组织间排斥反应的细胞成分，保留细胞外基质成分即细胞支架结构，以“细胞支架”的形式移植到受体部位，为细胞提供生长的场所和空间，诱导和调节细胞的生长、分化和代谢。我科在2003年以来使用了异体脱细胞真皮软组织修复材料修复口腔颌面部口腔黏膜缺损，并取得了较满意的效果。     

补气通窍方灌胃对大鼠变应性鼻炎的治疗作用及其机制

目的 通过建立大鼠变应性鼻炎（AR）模型,观察补气通窍方对大鼠AR的治疗作用并分析其机制。方法 将Wistar大鼠随机分为对照组、模型组、补气通窍方组及鼻炎康组,每组10只。除对照组外均使用卵清蛋白抗原佐剂混悬液建造AR模型,建模成功后,模型组给予4 mL/d纯净水灌胃,补气通窍方组给予补气通窍方57.55g/（kg·d）灌胃,鼻炎康组给予鼻炎康462.5 mg/（kg·d）灌胃,对照组常规饲养不灌胃,共灌胃7 d,每日1次。各组每次灌胃结束后观察大鼠30 min内抓鼻、喷嚏及流涕的症状发生情况并计算动物行为学积分;HE染色观察鼻黏膜组织病理学改变;Western blotting法检测脾脏组织NF-κB p65蛋白;16 S rRNA基因测序检测肠道菌群多样性及丰度。结果 模型组、补气通窍方组及鼻炎康组各时点动物行为学积分均高于对照组;灌胃2 d后,补气通窍方组动物行为学积分均低于模型组;灌胃3 d后,鼻炎康组动物行为学积分均低于模型组（P均<0.05）。对照组鼻黏膜假复层纤毛柱状上皮清晰可见,固有层无水肿、充血等病理改变;模型组鼻黏膜纤毛排列杂乱,可见较多嗜酸性粒细胞等炎症细...     

扶正化瘀方对骨髓细胞在纤维化肝脏中迁移与分化的干预作用

[目的]探究扶正化瘀方(Fuzheng Huayu recipe,FZHY)对骨髓细胞在肝纤维化形成中向肝脏迁移与分化的干预作用.[方法]以绿色荧光蛋白(green fluorescent protein,GFP)标记的供体ICR小鼠的骨髓细胞移植入受体ICR小鼠,8周后进行受体外周血GFP鉴定,并分为移植后对照组与移植后模型组,移植后模型组予二甲基哑硝胺(Dimethylnitrosamine,DMN)诱导肝纤维化,4周后移植后模型组进一步分为移植+DMN组、移植+DMN+肝细胞生长因子(hepatocyte growth-promotting factors,pHGF)组与移植+DMN+ FZHY组,pHGF与FZHY分别给药8周后,免疫荧光检测肝组织的GFP、白蛋白(Albumin,Alb)、α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)及CD32的表达.[结果]移植8周末受体外周血涂片可见大量GFP;给药12周末,移植+DMN+ FZHY组纤维间隔与肝实质区均可见GFP,实质区可见Alb,未见GFP+/Alb+,纤维间隔内可见GFP+/α-SMA+,但与移植+ DMN组相比明显减少,窦状隙可见CD32+,可见明显GFP+/CD32+.[结论]在本实验建立的骨髓细胞移植后受体肝纤维化形成的体内微环境下,FZHY给药后,骨髓细胞有向肝实质区迁移的趋向,未能向肝细胞分化,可逆转其向肌成纤维细胞的分化失衡,可部分转分化为肝窦内皮细胞.     

Cellular sequence of tracheal repair in sheep after smoke inhalation injury

The cellular repair process of injured tracheal epithelium is described for sheep after exposure to toxic smoke containing high concentrations of acrolein. Fourteen fasted 3–4-year-old ewes had a portion of their cervical trachea exposed to cotton smoke for 20 min and then were sacrificed at various time intervals ranging from 1 to 22 days after exposure. Within 1 day of injury, columnar epithelium sloughed intact from the trachea with a concomitant reduction of nearly 35% in the basal cell population. At 2 days of recovery, the cellularity of the epithelium had increased and mitotic figures were observed in some tracheal epithelial and gland cells. By 8 days, undifferentiated hyperplastic cells increased to 30/100 µm, differentiated nonciliated columnar cells first appeared, and the basal cell population returned to a normal count of 13 cells/100µm. Thirteen days after exposure, the undifferentiated hyperplastic cell population had declined to 7 cells/100/ µm, nonciliated columnar cells were at control values, and some ciliated cells were identified. At 18 and 22 days, epithelium was normal in appearance and the count was 13 cells/100µm. Data suggest that because the columnar epithelium sloughs intact with the cilia remaining active, toxic smoke may affect their attachment to the basal lamina. Furthermore, the regeneration process involves differentiation of hyperplastic cells in which they elongate down to the basal lamina, thus re-establishing the integrity of tall, epithelium in the sheep trachea. Offprint requests to: R. E. Barrow     

Growth factors accelerate epithelial repair in sheep trachea

Toxic gases and fumes have been shown to be injurious to the upper airways. Repair of this injury involves proliferation and migration of surviving nonciliated cells, followed by differentiation to a normal phenotype. Because recent results suggested that growth factors could improve the outcome of an airway injury, we undertook this study to determine the efficacy of these materials as an initial treatment to accelerate the healing process. In 24 anesthetized sheep, a portion of the trachea was exposed to smoke from smouldering cotton cooled to 37°C. Twelve received aerosolized epidermal growth factor plus platelet derived growth factor, while twelve received placebo. At 10 days after injury, nonciliated and ciliated cells were totally absent in the injured trachea receiving the placebo. In animals receiving growth factors, nonciliated and ciliated cells, however, were present (56% and 31% of uninjured trachea, respectively). At 13 days after injury, nonciliated and ciliated cell counts in those receiving placebo were 67% and 33% of uninjured, respectively. In sheep receiving growth factors, tracheal nonciliated and ciliated cell counts had increased to 105% and 64% of uninjured trachea, respectively. We conclude that growth factors therapy after airway injury stimulates cell proliferation and differentiation, and this therapeutic intervention to accelerate the repair process in acute airway injury is an approach applicable to humans. Offprint requests to: R. E. Barrow     

Cardia-type metaplasia arising in the remnant esophagus after cardia resection

BACKGROUND: Specialized intestinalized metaplasia in the distal esophagus (Barrett's esophagus) is a recognized precursor of esophageal adenocarcinoma, but its pathogenesis is incompletely understood. The aim of this study was to investigate the mucosal effects of esophagogastrostomy, an artificial interface between esophageal squamous and gastric oxyntic epithelium. METHODS: EGD was performed in 14 consecutive patients (median age 63 years, range 26-71 years) who had undergone esophagogastrostomy from 3 to 88 months earlier. Biopsy specimens were obtained in 13 patients from the anastomosis and, when present, columnar epithelium in the remnant esophagus. RESULTS: In 10 patients, EGD demonstrated tongue-shaped segments of columnar epithelium extending from 0.3 to 7 cm into the remnant esophagus. Biopsy specimens revealed cardia-type mucosa in all patients, whether at the anastomosis or proximally in esophageal segments of columnar epithelium. Magnification endoscopy of cardia-type mucosa visualized a long-oval, tubular, or ridged surface pattern. In 3 cases, complete intestinal metaplasia was observed within the cardia-type mucosa. CONCLUSIONS: The frequent transformation of squamous epithelium into cardia-type mucosa in the distal remnant esophagus after esophagogastrostomy supports the concept that cardia-type mucosa is a reflux-induced metaplasia that may give rise to the subsequent development of specialized intestinalized metaplasia.     

Substitution of the wall of the trachea by absorbable synthetic material

Synthetic, absorbable tissue proved to supply a valuable "interim support" for an orderly reconstruction of the wall of the trachea during the first three months following surgery. This is in general the result of experiments in which the use of implanted Polyglactin 910 as a substitute material for the tracheal wall of rats and rabbits was tested. Additionally the possibilities for satisfactory stabilization of the tracheal wall by means of Polydioxanon, another synthetic substance, which is absorbed more slowly, were investigated. The experiments were performed in a total of 30 rats and 70 rabbits. Initial attempts to substitute the entire circumference of the tracheal wall in the area of the neck by synthetics resulted in excessive difficulties post-surgically. Frequently substantial stenoses, obstructing respiration, developed. Consequently, patches of substitute material, covering more than half of the circumference of the trachea, were applied. The periods of survival of the animals ranged from one to 23 weeks. Following autopsy and macroscopical inspection, selected specimens were examined histologically by means of light microscopes and scanning electron microscopes. Evaluation of the samples showed progressive lining of the inner surface of the prosthetic patches with connective tissue and subsequent covering with squamous cell epithelium. On the average, approximately six weeks after surgery, ciliated columnar epithelium resembling normal respiratory mucosa developed. Gradually the synthetic fabric was replaced by dense connective tissue, which finally contained newly generated hyaline cartilage also. The very slow rate of dissolution of the polydioxanone material provided sufficient time for the formation of a new, stratified wall of the trachea, maintaining sufficient clearance in the tracheal lumen.     

Experimental carinal replacement with an Y-shaped collagen-conjugated prosthesis

BACKGROUND: A new prosthesis was designed for reconstruction of the bifurcation of the trachea and used for experimental carinal replacement in dogs. METHODS: The main Frame of the new prosthesis consists of Y-shaped Marlex mesh tube reinforced with polypropylene spirals. It is coated with collagen extracted from porcine skin to provide biocompatibility and airtightness. Carinal replacement with omentopexy was performed in 17 dogs. RESULTS: Seven dogs survived the postoperative period, and 10 dogs died within 11 days after the operation. The main causes of early postoperative death were fistula and air leakage from the prosthesis. Causes of late postoperative death were obstruction of the main bronchus (two) and lung abscess (one). The four long-term survivors had no stenosis or dehiscence until they were sacrificed 15 months after the operation. Histological examination of these dogs revealed that the luminal surface was covered either with ciliated columnar epithelium or non-ciliated squamous epithelium. CONCLUSIONS: The study results suggest the possibility of successful prosthetic carinal reconstruction with epithelial regrowth using this Y-shaped prosthesis.     

Experimental reconstruction of dog's esophagus with biotype artificial esophagus

OBJECTIVE: At present, there are few materials available for esophagus reconstruction anywhere in the world. The reported survival rate in animals during the perioperative period is comparatively low. The present study assessed the feasibility of using a biotype artificial esophagus in the reconstruction of a dog's esophagus. METHODS: In 30 mongrel dogs, a portion of the thoracic esophagus was resected and an 8 cm section of artificial esophagus was transplanted to reconstruct the organ. The survival rate, food intake and process of healing were observed. RESULTS: Of the 30 dogs, 28 survived the peri­operative period (93.3% survival). Two dogs (6.7%) developed an anastomotic fistula; 19 dogs survived for 1 year, a survival rate of 79.2% (19/24) with the remaining six dogs were killed according to the experimental protocol. Detachment of the artificial esophagus occurred on average 28.8 days after operation and the dogs suffered from varying degrees of dysphagia 23?45 days after operation. Gradual remission occurred after 4 months. The histological study revealed that the regenerated esophagus was composed of fibrous and connective tissues and the luminal surface was covered with squamous epithelium in 3?6 months. CONCLUSION: The transplanted artificial esophagus detached after the surrounding ‘regenerated esophagus’ had formed, and the squamous epithelium gradually covered the luminal surface. Continuous remodeling of the ‘regenerated esophagus’ gradually relieved the stenosis. Whether detachment of the implant and the postoperative stenosis can be solved is the key problem restricting the use of the biotype artificial esophagus in clinical practice.     

Omentopexy for revascularization of free tracheal grafts in rats.

In rats, we examined the effect of an omentum wrapping on the vascularization of the trachea and on regeneration of the mucosal epithelium in the very early stage after free tracheal grafting. Two pieces of trachea were obtained from each donor rat. One piece was transplanted into the peritoneal cavity of the recipient rat and wrapped with omentum. The other piece was transplanted subcutaneously into the abdominal wall, without omentopexy. Recipients were sacrificed at random on days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels rose significantly earlier in the omentopexy tracheas than in those without omentopexy (p less than 0.01), with all the former showing a normal ciliated, columnar epithelium in the membranous region of the trachea on day 4, accompanied by excellent epithelial regeneration in the cartilaginous region. These results suggest that omentopexy causes revascularization to occur earlier and to be completed in a shorter time, and that it also promotes epithelial regeneration following free tracheal grafting.     

Complete regression of Barrett's esophagus with heat probe thermocoagulation: mid-term results.

BACKGROUND: Barrett's esophagus is a premalignant condition. It has been reported that several methods of endoscopic ablation in combination with acid suppression result in replacement of specialized columnar epithelium by squamous epithelium. The aim of this study was to assess whether ablation of Barrett's mucosa by means of heat probe and acid suppression restores normal esophageal mucosa. METHODS: Thirteen patients with Barrett's epithelium but not dysplasia were enrolled in the study. Helicobacter pylori was eradicated when discovered. Thermal energy was applied using a heat probe (pulses of 5 to 10 joules). Four-quadrant biopsies were obtained at 1 to 2 cm intervals 1 to 3 months after the last treatment session. All patients continuously took omeprazole, 40 mg/day. RESULTS: Macroscopically, ablation of Barrett's mucosa was achieved in all patients after 1 to 5 sessions. Three of the 13 patients had residual specialized columnar epithelium beneath the restored mucosa but not overexpression of p53 and c-erbB-2. During follow-up (6 to 36 months) two patients in whom the length of Barrett's mucosa was greater than 2.5 cm relapsed after omeprazole discontinuation, whereas another two with length of less than 2.5 cm did not. One patient with residual Barrett's islands developed low-grade dysplasia. CONCLUSIONS: Heat probe is an effective and inexpensive method for Barrett's ablation. Islands of residual specialized columnar epithelium were found in 23% of patients. The length of Barrett's epithelium determines relapse after omeprazole discontinuation. (Gastrointest Endosc 1999;50:165-72).     

A case of foregut gastric duplication cyst with pseudostratified columnar ciliated epithelium

Gastrointestinal duplication is a congenital rare disease. Duplication cyst of the stomach with pseudostratified columnar ciliated epithelium is extremely rare. A 44-year-old Japanese woman visited University of Yamanashi Hospital for evaluation of an abnormal tumor detected by abdominal ultrasonography at an annual general health examination. Abdominal computed tomography indicated a subserosal cystic lesion 6 cm in diameter on the posterior wall of the stomach. The cystic lesion was resected through partial resection of the stomach. Histopathology showed that the cyst did not communicate with the gastric lumen, was covered with gastric epithelium and pseudostratified columnar ciliated epithelium with circular muscle layers, and did not contain cartilaginous tissue. Consequently, the patient was diagnosed as having foregut duplication cyst of the stomach. Gastrointestinal duplication can occur in any region of the gastrointestinal tract, but foregut duplication cyst of the stomach is rare. The present case was a subserosal cyst on the greater curvature that did not communicate with the gastric lumen and was covered with gastric epithelium and pseudostratified columnar ciliated epithelium, suggesting a foregut cyst caused by an aberrant respiratory organ.     

Effects of irradiation on canine tracheal epithelium: a physiological and morphological correlate

We delivered 20 Gy irradiation in one fraction to a 6 cm segment of trachea in 11 dogs. Tracheal mucous transport was studied before and whenever possible at weekly intervals after irradiation using a gamma camera system and 99m technetium labeled sulfur colloid. Ten of the eleven animals were sacrificed at three different time intervals (1-2, 15-16 and 30-34 weeks) post-irradiation, and the tracheal epithelium removed for studies using Ussing chambers followed by preparation for microscopic analysis. Mucous transport along the length of the trachea was normal before irradiation, but following irradiation it became abnormal in the irradiated zone. Compared to the epithelium from the cranial and caudal segments, the irradiated epithelium had similar bioelectric measurements (potential difference, short-circuit current and resistance) and mannitol permeability. Also, the changes in the bioelectric measurements following indomethacin (10(-6) M) and epinephrine (10(-6) M) used sequentially, were similar in both the control and irradiated tissues. Scanning electron microscopic analysis of the irradiated zone revealed patches of nonciliated epithelial cells among the ciliates. We conclude that irradiation caused a persistent replacement of ciliated cells with nonciliates throughout the entire study period and that this alteration impaired mucous transport but did not affect epithelial ion secretion or barrier function.