纤维蛋白生物胶外周支持对大鼠颈静脉移植物的增殖和凋亡的影响

目的研究纤维蛋白胶血管外周支持对静脉移植物平滑肌细胞增殖、凋亡的影响。方法建立大鼠颈总动脉自体颈静脉移植模型,按照有无纤维蛋白胶血管外周支持,分为外周支持组、无外周支持组,每组24只。术后1周、2周、4周分别切除移植静脉,用免疫组织化学方法检测静脉移植物平滑肌细胞增殖细胞核抗原(PCNA)表达,用原位DNA断裂位点3’-羟基末端标记(TUNEL)法检测静脉移植物平滑肌细胞凋亡的变化,以及检测内膜厚度。结果静脉移植术后1-4周,无外周支持组静脉移植物血管平滑肌细胞的凋亡和增殖均明显升高,内膜明显增厚;纤维蛋白胶血管外周支持组静脉移植物血管平滑肌细胞的凋亡和增殖同处于低水平,内膜增厚不明显。两组静脉移植物血管平滑肌细胞的凋亡和增殖具有显著相关性。结论纤维蛋白胶外周支持可以抑制血管平滑肌的增殖和凋亡,使两者同时处于低水平,一方面减少细胞凋不足所造成的对血管重塑造成的影响,另一方面使凋亡程度与巨噬细胞及正常血管平滑肌吞噬作用达到平衡,抑制了静脉移植物的内膜增生。     

NiTi放射性支架置入兔腹主动脉后对平滑肌细胞增殖和凋亡的影响

目的　观察NiTi放射性支架对平滑肌细胞增殖和凋亡的影响。方法　在 76只家兔腹主动脉中分别置入放射与非放射性支架。用免疫组化法和TUNEL法观察放射性支架对平滑肌细胞增殖和凋亡的影响。结果　 (1) 2周时放射与非放射性组新生内膜面积无显著差异 (P >0 0 5 ) ,1个月和 3个月时放射支架组新生内膜面积小于非放射性组 (P <0 0 1) ;(2 )PCNA法测定平滑肌细胞增殖显示放射性组在各时间点PCNA表达低于非放射性组 (P <0 0 5 ) ;(3)TUNEL法测定放射性组平滑肌细胞凋亡与对照组相比在 2周和 1个月时有显著差异 (P<0 0 5 ) ,在 3个月时两组平滑肌细胞凋亡无显著差异 (P >0 0 5 )。结论　 (1)放射性支架可减少支架置入术后支架内新生内膜面积。 (2 )放射性支架可抑制血管平滑肌细胞增殖。 (3)放射性支架促进血管平滑肌细胞凋亡     

冠状动脉不稳定斑块中平滑肌细胞和炎性细胞PCNA阳性及TUNEL阳性细胞分布特点

目的　探讨增殖细胞核抗原 (PCNA)的表达和细胞凋亡在人冠状动脉不稳定斑块中的作用。方法　取人冠状动脉不稳定斑块标本 2 3例 ,采用免疫组织化学技术SP法检测细胞PCNA表达原位末端标记法 (TUNEL)检测细胞凋亡。结果　纤维帽区与肩部炎性细胞PCNA表达显著高于其余二区 ;脂核区平滑肌细胞、炎细胞TUNEL阳性细胞数明显高于其余三个区。纤维帽和肩部中平滑肌细胞和炎细胞PCNA阳性表达大于TUNEL阳性细胞数 (P <0 0 5;P <0 0 1) ;脂核内TUNEL阳性细胞明显大于PCNA阳性表达细胞 (P <0 0 1)。结论　冠状动脉不稳定斑块内细胞凋亡主要发生在斑块脂核周围 ,炎细胞的增殖主要发生在斑块的肩部     

冠状动脉支架置入后局部内膜增生模式的探讨

目的探讨冠状动脉支架置入局部血管内膜的增生模式。方法建立冠状动脉支架置入的广西种的微型猪模型。分别于支架置入后3,7,28,90和180 d截取支架段血管连同临近的近端正常血管段,进行病理组织学检查和聚合酶链反应检测支架局部血管内膜增生情况。结果正常血管段表达增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)mRNA在各个时间段没有显著性差异。支架置入后3 d局部血管壁PCNA mRNA的表达明显增高。并在术后7 d达到高峰。术后90 d PCNA mRNA的表达呈现下降的趋势,但仍显著高于正常血管段,并且差异一直持续到术后180 d。术后7～180 d支架段内膜及中膜面积明显大于正常血管段。结论冠状动脉支架置入后局部内膜呈现了一种持续过度的增生反应。     

103 Pd支架预防支架内再狭窄的量效及机制

目的　探讨1 0 3Pd支架对血管成形术后再狭窄的预防作用的量效关系及其机制。方法　5 0只雄性新西兰白兔随机分为普通支架组和各剂量的核素支架组 (8只 组 )。支架置入术后 8周行腹主动脉血管内超声和造影检查、行免疫组化染色并检测细胞凋亡。结果　在核素支架组 ,随剂量增加 ,支架段最小内径和支架内管腔面积均增大而狭窄程度减小。核素支架各组增殖细胞核抗原(PCNA)阳性细胞率均显著小于普通支架组 ,而凋亡指数除 5Gy组外均显著大于普通支架组。结论　1 0 3　Pd支架可抑制支架内血管内膜的增生 ,减少支架内狭窄的程度 ,显示出量效关系。1 0 3Pd支架既抑制血管平滑肌细胞 (VSMC)增生也诱导细胞凋亡。     

重组水蛭素局部治疗球囊扩张术后内膜增殖和管腔狭窄的实验研究

目的 :探讨重组水蛭素经多孔球囊导管局部治疗兔髂总动脉球囊扩张术后内膜增殖和管腔狭窄的作用。方法 :2 4只纯种日本大耳白兔随机分成对照组 （n=12 ）和重组水蛭素局部治疗组 （n=12 ） ,采用兔髂总动脉球囊扩张术后内膜增殖和管腔狭窄动物模型 ,治疗组经多孔球囊导管于球囊扩张局部在 2个大气压下给予重组水蛭素 re-fludin（14 .5× 10 6 ATU· g- 1 ） 1m g· kg- 1 ,对照组给予生理盐水。术后 2周和 4周复查血管造影 ,术后 4周取髂总动脉标本行 HE染色、Masson三色染色、平滑肌肌动蛋白 （α- actin）免疫组织化学染色和增殖细胞核抗原 （PCNA ）免疫组织化学染色 ,并进行计算机图象分析。结果 :治疗组术后 2周和 4周血管造影平均髂总动脉直径分别较对照组扩大 5 9.9% （P<0 .0 1）和 6 1.6 % （P<0 .0 1） ,平均髂总动脉面积分别较对照组扩大 135 .6 % （P<0 .0 1）和 191.1% （P<0 .0 1）。图象分析示球囊扩张术后 4周治疗组髂总动脉血管腔面积较对照组扩大 113.0 4 % （P<0 .0 1） ,管壁面积和内膜面积分别减少 2 9.2 0 % （P<0 .0 1）和 82 .0 0 % （P<0 .0 1）。术后 4周治疗组球囊扩张血管壁α- actin和 PCNA免疫组化染色阳性细胞均较对照组明显减少。结论 :重组水蛭素经多孔球囊导管局部治疗 ,可显著减轻兔髂总动脉     

大鼠胸主动脉球囊损伤对细胞凋亡及凋亡相关基因Fas、Bcl-2表达的影响

目的探讨大鼠胸主动脉球囊损伤后细胞凋亡和凋亡相关基因表达的变化规律。方法将30只400~500 g的雄性SD大鼠随机分为2组,手术组(n=24)行球囊扩张损伤大鼠胸主动脉术;对照组(n=6)不行球囊损伤,作为正常对照。分别于术后2、7、14、28 d取胸主动脉应用HE染色、TUNEL法、免疫组化和计算机图像分析仪进行形态学、细胞凋亡、增殖细胞核抗原(PCNA)、凋亡基因Fas;抗凋亡基因Bcl-2表达水平检测。结果对照组管壁处于非增殖状态;手术组球囊损伤后7 d形成新生内膜,血管平滑肌细胞(VSMC)增殖活跃;14 d内膜明显增厚,但VSMC增殖已减弱;28 d内膜继续缓慢增厚,管腔明显狭窄。动脉损伤后Fas表达和TUNEL法测定的凋亡规律一致,两周内凋亡较明显,但细胞凋亡高峰时间(中膜7 d、内膜14 d)迟于增殖高峰(中膜2 d、内膜7 d),两周后凋亡与增殖均明显下降。动脉损伤后抗凋亡基因Bcl-2表达下调,在中膜和内膜分别在7 d1、4 d达最低水平,后回升,与凋亡基因Fas表达呈明显负相关(r=-0.878,P<0.001)。结论动脉球囊损伤后,平滑肌细胞的凋亡呈现规律性变化,可能在管腔狭窄的病理过程中具有重要作用。     

新型血管内可吸收镁合金支架的实验研究

目的评估自行设计制作的新型血管内可吸收镁合金支架的生物相容性、有效性和安全性。方法杂种犬35只,每只犬均于冠状动脉和股动脉置入可吸收镁合金支架1枚,分别于术后1、3、5 d和1、2、3、4周,每个时间点5只犬,复查冠状动脉和股动脉,血管造影后取材,分离支架段血管行组织病理观察及计算机图像分析,测量内弹力板面积、管腔面积、内膜增生面积及内膜增生面积百分比。结果 51枚支架成功置入35只犬的冠状动脉和股动脉,各时间点冠状动脉及股动脉造影均证实管腔通畅,无狭窄病变,无血栓形成。组织病理显示,支架置入术后1、3、5 d无内膜增生,仍有支架残留;1周支架完全降解;2周开始出现内膜增生,3周至4周内膜增生相对明显。各时间点均未见明显炎性反应和血栓形成;术后2、3、4周,内膜增生面积分别为(0.04±0.03)mm~2,(0.10±0.03)mm~2,(0.15±0.04)mm~2;内膜增生面积百分比分别为(1.84±1.18)%,(3.72±1.12)%,(6.29±3.36)%,差异有统计学意义(P<0.05)。结论血管内可吸收镁合金支架具有良好的生物相容性,安全有效,易操作,再狭窄程度轻,临床应用前景好。     

骨髓间充质干细胞移植对兔颈动脉球囊损伤后再狭窄的影响

目的 探讨兔颈动脉行球囊损伤后,骨髓间充质干细胞(BMSC)移植对损伤血管内皮修复和再狭窄的影响.方法 建立兔颈动脉粥样硬化狭窄模型48只,随机分成BMSC移植组24只和对照组24只.体外培养BMSC,携带增强型绿色荧光蛋白(EGFP)的腺病毒转染标记后备用.颈总动脉球囊损伤后,以107个/kg的细胞数经颈外动脉移植到损伤动脉局部,对照组注射等量的PBS液.移植后1周取材行免疫组织化学检测BMSC归巢.移植后2周免疫组织化学染色检测血管内膜血小板-内皮细胞黏附分子(CD31)、α-平滑肌肌动蛋白(SM α-actin)及增殖细胞核抗原(PCNA)的表达;移植后4周行颈总动脉造影检测血管狭窄率,HE染色检测损伤血管新生内膜面积、新生内膜面积/中膜面积的变化.结果 BMSC移植组在术后1周损伤血管的内膜有表达EGFP的BMSC归巢.术后2周BMSC移植组血管内膜有连续性CD31的表达,对照组为阴性;BMSC移植组PCNA的表达较对照组明显降低(23.43％±2.80％比50.49％±3.60％,P＜0.05),而BMSC移植组SM α-actin的表达较对照组明显增加(0.437±0.049比0.197 ±0.032,P＜0.01).术后4周HE结果显示:BMSC移植组血管新生内膜面积(0.103±0.022比0.214±0.024,P＜0.01)、新生内膜/中膜面积(0.771±0.096比1.646±0.223,P＜0.01)均较对照组减轻;颈动脉造影结果显示:BMSC移植组较对照组血管再狭窄率减轻(39.64％±2.30％比63.31％±2.82％,P＜0.05).结论 移植BMSC可促进颈动脉球囊损伤后早期再内皮化和血管平滑肌细胞表型转化,抑制血管新生内膜的增生,减轻了血管再狭窄.     

犬冠状动脉内血浆包膜支架的生物相容性研究

目的 :评价血浆包膜支架在犬冠状动脉内的生物相容性。方法 :分别在犬左冠状动脉的回旋支和前降支随机植入 1个血浆包膜支架和 1个裸支架 ,术后 3d和 15 d（n=4）扫描电镜观察血小板粘附和血管内膜的内皮化情况 ,术后 1月 （n=5 ）进行冠脉造影和光镜检查。结果 :支架植入术后 3d,血浆包膜支架组和裸支架组的血小板粘附数无显著差异 （P>0 .0 5 ） ;术后 15 d,两组血管内膜均完全被新生内皮细胞覆盖 ;术后 1月 ,两组血管的损伤程度相同 ,冠脉造影和病理学检查均显示 ,两组的狭窄程度无区别 ,血管壁无大量的异物巨细胞聚积。结论 :血浆包膜支架具有良好的生物相容性     

骨髓间充质干细胞移植加重大鼠主动脉血管成形术后再狭窄程度

目的探讨骨髓间充质干细胞（MSCs）移植对大鼠血管成形术后再狭窄的影响。方法随机将大鼠分为正常对照、损伤和损伤加MSCs移植组,用经皮冠状动脉腔内成形术（PTCA）导管扩张大鼠胸腹主动脉创建动脉损伤模型。贴壁法培养大鼠MSCs,经4,6-联脒-2-苯基吲哚（DAPI）荧光标记后,以2×10^6数量经导管注入移植组大鼠主动脉内。术后第1、2、6周取材寻找DAPI标记的MSCs,行组织形态学及血小板衍生的生长因子受体（PDGFR）家族干细胞因子的受体（c—kit）,增殖细胞核抗原（PCNA）,平滑肌肌动蛋白（αSMA）免疫组化分析。结果移植术后1～2周,可见DAPI标记MSCs归巢到损伤内膜表面或中膜近内膜处,并表达d—SMA。移植组和损伤组新生内膜表面均表达少量c-kit,两组之间无明显差别。正常对照组血管中膜α-SMA均匀强表达,PCNA表达微弱,无新生内膜。移植组新生内膜中PCNA和α—SMA表达均强于损伤组。术后6周,移植组新生内膜／中膜面积百分比和管腔面积狭窄率均较损伤组明显增加,差异具有统计学意义。结论经主动脉移植的骨髓MSCs可归巢到严重受损的主动脉内膜上,并分化为平滑肌样细胞,参与新生内膜的形成,加重大鼠血管成形术后再狭窄程度。     

Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model

OBJECTIVES: We sought to evaluate whether cellular mass changes (including apoptosis and proliferation) after arterial injury could interact with restenosis and arterial remodeling. BACKGROUND: The mechanisms controlling arterial remodeling after angioplasty remain poorly understood. Apoptosis and cell proliferation have been previously described after balloon angioplasty. However, their importance in the occurrence of arterial remodeling and restenosis is unknown. METHODS: Atherosclerosis was induced in 48 femoral arteries of New Zealand White rabbits by air-desiccation and a high-cholesterol diet. One month later, angioplasty was performed in 40 arteries. Apoptosis, cell proliferation, residual stenosis and arterial remodeling were evaluated at 2 h and 3, 7, 14, 21 and 28 days after angioplasty. RESULTS: Cell proliferation and apoptosis profiles were similar, but the peak in cell proliferation occurred approximately four days earlier than the peak in apoptosis in the neointima and media. Apoptosis density was positively correlated with arterial remodeling in the neointima and media (r = 0.69, p = 0.005 and r = 0.50, p = 0.05, respectively). Moreover, residual stenosis was inversely correlated with apoptosis density in the neointima and media (r = -0.62, p = 0.008 and r = -0.52, p = 0.04, respectively). In contrast, cell proliferation was independent of restenosis and arterial remodeling. CONCLUSIONS: In this model, cell proliferation preceded apoptosis throughout the four weeks after angioplasty. Apoptosis was inversely correlated with restenosis. Interestingly, apoptosis was also related to enlargement remodeling after balloon angioplasty.     

Morphological and histological studies of in-stent restenosis in seven types of stents implanted in porcine coronary arteries]

OBJECTIVES: Differences in the mechanism of restenosis after stenting between coil and tubular stents were examined in porcine coronary arteries using histological and immunohistochemical methods. METHODS: Twenty-four pigs underwent balloon-induced injury in the left anterior descending coronary artery. Two weeks later, seven different stents clinically available in Japan (Coil stents: GR I, GR II, Wiktor, Cordis; Tubular stents: gfx, Multilink, Palmaz-Schatz) were implanted in the injured site. Four weeks after the stent implantation, the pigs were sacrificed for histological examination and for morphometrical analysis of the lumen, neointima, media and adventitia. Immunohistochemical studies using anti-proliferating cell nuclear antigen (PCNA), anti-alpha-smooth muscle actin and anti-macrophage antibody were also performed. RESULTS: The coil stents formed eccentric, and the tubular stents formed concentric neointimal proliferation. Although there was no difference in the area of neointima between the stents, the area of lumen in the tubular stents was bigger than that in the coil stents (p < 0.01), because the vascular area was bigger in the tubular stents (p < 0.05). Immunohistochemical examination found many PCNA-positive cells in the proliferated neointima, especially in the area around the stent strut. Many of these cells around the stent strut were positively stained by anti-macrophage antibody. Other cells positively stained for PCNA were confirmed as smooth muscle cells. CONCLUSIONS: Tubular stents maintained a wider lumen than coil stents, because negative remodeling after stenting was less in the tubular stents. Implantation of stents with less negative remodeling is very important to prevent restenosis after stenting.     

XS0601对猪冠脉球囊损伤后内膜细胞凋亡及bcl-2、p53基因表达的影响

目的观察XS0601(由川芎和赤芍的有效部位组成)对猪冠状动脉球囊损伤后细胞凋亡及相关基因bcl-2、野生型p53表达的影响.方法球囊扩张损伤猪冠状动脉左前降支(LAD)中段内膜的方法建立再狭窄(RS)模型.其中对照组不给予特殊药物治疗,各药物组于术前2天开始给药,持续至术后4周处死.原位杂交方法观察球囊损伤后内膜中bcl-2、p53mRNA表达,原位末端标记法(ISEL)检测内膜中的凋亡细胞,并研究药物对细胞凋亡的影响.结果损伤后4周动脉在内弹力板(IEL)断裂情况下,形成了明显的新生内膜.小剂量和大剂量XS0601均可增加内膜中的凋亡细胞,其凋亡细胞阳性表达面积率与对照组相比差异有显著性(P<0.01和P<0.05);并能减少内膜中的bcl-2阳性杂交颗粒,增加p53阳性杂交颗粒.结论猪冠状动脉球囊损伤后新生内膜中的细胞凋亡水平较低,凋亡抑制基因bcl-2的表达增加.XS0601可通过减少凋亡抑制基因bcl-2的表达,上调凋亡促进基因p53的表达,从而对猪冠状动脉球囊损伤后SMC增殖过程中较低的凋亡水平进行调控,诱导新生内膜中的细胞凋亡.     

Increased Apoptotic Cell Death in the Neointima after Stent-Based Vascular Irradiation: Role of Radiation-Induced Apoptosis for Restenosis Reduction

Background: Restenosis after stent implantation is a common problem faced today by interventional cardiologists. It is primarily caused by excessive neointimal growth. Early clinical studies showed substantial reductions of neointimal volumes within bodies of³²P radioactive coronary stents. Radiotherapy induces programmed cell death (apoptosis) in tumors but there is still debate whether irradiation causes apoptosis in arteries. Methods: We compared the time course of neointimal apoptosis after implanting 7-mm long ³²P radioactive slotted tubular stents in rabbit iliac arteries. The stents were homogeneously ion-implanted with ³²P at activity levels of 0.5 and 6 μCi. These stents produce continuous beta-particle emission at very low dose rates. Neointima formation was compared with nonradioactive stents by histomorphometry after 1, 4, and 12 weeks. Apoptosis was detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay method and transmission electron microscopy. Results: At an early follow-up of 1 week after stent implantation, no changes in neointimal apoptosis were found. The ³²P stents at activities of 6 μCi, but not of 0.5 μCi, reduced neointimal crosssectional areas and cell numbers compared with control stents after 4 and 12 weeks. Apoptosis in the neointima increased after 4 weeks and was substantially elevated 12 weeks after implantation of 6 μCi ³²P stents compared with 0.5 μCi and control stents (16% vs 6% and 3%, P < 0.01 for 6 vs 0.5 μCi and control stents, respectively). Conclusions: In this study, a dose dependent decrease in neointimal thickening and cell density within ³²P beta-particle emitting stents was associated with an increased frequency of apoptosis. This increase in apoptosis occurred late in the time course of vascular healing after the implantation of ³²P beta-particle emitting stents. Apoptosis seems to be involved in the mechanisms by which stent-based vascular irradiation reduces neointimal hyperplasia.     

Cell cycle regulator expression after coronary stenting in humans

Proliferation of vascular smooth muscle cells (VSMCs) is under the control of cell cycle regulator activity, which is induced by several growth factors. Recent attention has been drawn to treatments that target cell cycle regulators to prevent the proliferation of VSMCs after coronary angioplasty. However, histopathological evaluation of cell cycle regulator expression after human coronary stenting has not been sufficient. Thirty-one coronary arteries of 23 cadavers were examined. Time from stent implantation to patient death ranged from 0 to 235 days. Sections were stained with antibodies against platelet-derived growth factor (PDGF), basic fibroblast growth factor (b-FGF), cyclin D1, p16, p21, and p27. Staining for macrophage colony stimulating factor receptor (MCSF-R) was conducted to detect dedifferentiated VSMCs. MCSF-R-positive cells were observed in neointima but decreased in the late stage. PDGF was detected in neointima and decreased gradually. Expression of cyclin D1 appeared to be associated with the proliferation of VSMCs, whereas p27 was downregulated with the proliferation of neointima and upregulated in the late stage. Our results suggest that one of the most promising methods for preventing excessive proliferation of neointima after stenting is to limit the decrease in p27 or the increase in cyclin D1.     

镍钛自膨胀支架置入血管后细胞凋亡与增生的实验观察

目的　血管内支架置入后的再狭窄是尚未解决的主要课题 ,本研究对置入镍钛 (NITI)自膨胀支架的动物进行研究 ,观察支架置入后血管平滑肌细胞 (VSMC)的凋亡与增生的关系 ,为再狭窄的防治提供新的方法。方法　在兔的腹主动脉内置入 30个NITI合金自膨胀支架 ,按不同时间处死动物 ,采用电镜和 3′ 末端DNA原位标记法 (TUNEL)观察VSMC的凋亡。结果　从支架置入后的 2 4h到 8周 ,支架置入部位均可见到凋亡的VSMC ,3～ 6周时 ,凋亡达到高峰 ,8周以后凋亡细胞开始减少。凋亡的细胞主要分布于血管的新生内膜层 ,但中膜层也存在有少量的凋亡细胞。结论　NITI自膨胀支架置入后 ,不仅有SMC的增生 ,也有SMC的凋亡。     

Morphological changes of cell proliferation and apoptosis in rat jejunal mucosa at different ages

AIM: To study the changes of cell proliferation and apoptosis in rat jejunal epithelium at different ages. METHODS: Cell proliferation and apoptosis of the jejunal mucosal and glandulous epithelia from birth to postnatal 12(th) month were observed using immunocytochemistry (ICC), and TUNEL method. The height of villus, the thickness of muscle layer and the number of goblet cells in jejunal mucosal and glandulous epithelia were measured by BeiHang analytic software and analyzed by STAT. RESULTS: (1) Proliferating cell nuclear antigen (PCNA) positive cells of jejunal glandulous recess were found and increased in number from birth to the postnatal 3(rd) month. The number of PCNA positive cells peaked in the postnatal 3(rd) month, and decreased from then on. (2) The number of apoptotic cells also peaked in the postnatal 3(rd) month, showing a similar trend to that of the PCNA positive cells. (3) The height of jejunal villus increased after birth, peaked in the postnatal 3(rd) month and decreased from then on. The jejunal muscle layer became thicker in the postnatal 3(rd) week and the postnatal 12(th) month. The number of goblet cells of the jejunal mucosal and glandulous epithelia had a linear correlation with age. CONCLUSION: (1) PCNA positive cells are distributed in the jejunal glandulous recess. (2) Apoptotic cell number peaks in the postnatal 3(rd) month, indicating that cell proliferation and apoptosis are developed with the formation of digestive metabolism as rat grows to maturity. (3) The thickness of jejunal muscle layer increases to a maximum in the postnatal 3(rd) week, which may be related to the change in diet from milk to solid food. (4) The number of goblet cells increases rapidly in the postnatal 3(rd) week, probably due to ingestion of solid food.     

加味左金丸对胃癌前病变大鼠胃黏膜组织细胞增殖与凋亡的影响

[目的]探讨加味左金丸对胃癌前病变大鼠胃黏膜组织细胞增殖与凋亡的影响。[方法]将以饮用甲硝基亚硝基胍为主24周制成的胃癌前病变模型大鼠随机分为模型组，维甲酸组，加味左金丸高、中、低剂量组，治疗16周，采用免疫组化SP法，TUNEL法检测胃黏膜组织细胞增殖细胞核抗原（PCNA）、Bcl-2蛋白及凋亡指数（AD）的表达情况。[结果]加味左金丸能明显下调胃癌前病变组织细胞的PCNA、Bcl-2的表达，上调AI。[结论]抑制细胞增殖，诱导细胞凋亡可能是该方的作用机制之一。