不同浓度罗哌卡因浸润麻醉对大鼠切口愈合的影响

目的 评价不同浓度罗哌卡因浸润麻醉对大鼠切口愈合的影响.方法 健康成年雄性SD大鼠75只,体重220～ 250 g,采用随机数字表法,将大鼠随机分为5组(n=15):自然愈合组(C组)、生理盐水组(NS组)、0.20％罗哌卡因组(R0.20组)、0.50％罗哌卡因组(R0.50组)和0.75％罗哌卡因组(R0.75组).C组对皮肤切口不做任何处理,R0.20组、R0.50组和R0.75组分别于切皮前10 min时皮下注射0.20％、0.50％和0.75％罗哌卡因1.0 ml/kg,NS组注射等容量生理盐水.每组取5只大鼠,记录切口愈合时间;每组取10只大鼠,于术后72 h时记录切口长度,取切口周围皮肤组织,HE染色,光镜下计数成纤维细胞数量,masson染色,测定胶原表达,并测定IL-1β含量及其mRNA表达.结果 与C组比较,R0.20组切口愈合时间和切口长度缩短,皮肤组织成纤维细胞数量和胶原表达增加,R0.50组切口愈合时间和切口长度缩短,皮肤组织成纤维细胞数量和胶原表达增加,皮肤组织IL-β含量和IL-1βmRNA表达降低,R0.75组切口愈合时间和切口长度延长,皮肤组织成纤维细胞数量、胶原表达、IL-β含量和 IL-1β mRNA表达降低(P＜0.05),NS组上述指标差异无统计学意义(P＞0.05);与R0.20组比较,R0.50组切口愈合时间和切口长度缩短,皮肤组织成纤维细胞数量和胶原表达增加,皮肤组织IL-β含量和IL-1β mRNA表达降低,R0.75组切口愈合时间和切口长度延长,皮肤组织成纤维细胞数量和胶原表达降低,皮肤组织IL-β含量和IL-1βmRNA表达降低(P＜0.05);与R0.50组比较,R0.75组切口愈合时间和切口长度延长,皮肤组织成纤维细胞数量和胶原表达、IL-β含量和IL-1β mRNA表达降低(P＜0.05).结论 0.20％罗哌卡因及0.50％罗哌卡因浸润麻醉均可促进大鼠切口愈合,且0.50％罗哌卡因浸润麻醉促进切口愈合的效果优于0.20％罗哌呀因,0.75％罗哌卡因可抑制切口愈合.     

IFN-γ对大鼠创面愈合中Smad7表达的影响

目的：将干扰素γ（IFN-γ）应用于大鼠创面,观察创面肉芽组织的生长、成纤维细胞数目,分析IFN—γ对Smad7的影响。方法：选取成年SD大鼠127只,建立大鼠创伤模型。实验分成A、B、C、D、E共5组,每组25只。A组为生理盐水溶剂对照组,B组为IFN—γ 500U／ml溶剂剂量组,C组为IFN—γ 1000U／ml溶剂剂量组,D组为2000U／ml溶剂剂量组,E组为空白组,正常对照组2只,为未损伤的正常大鼠。分别于创伤第3、7、10、14、21日随机选取各组5只大鼠采用过量麻醉处死,剪取创面肉芽组织,分别行HE常规染色,在光学显微镜下观察新生肉芽组织厚度、计数成纤维细胞数。行免疫组化染色,在光学显微镜下观察肉芽组织中Smad7的表达情况。结果：各时间点A、B组肉芽组织厚度较C、D组致密且厚（P〈0．001）,E组肉芽组织厚度介于A、B组和C、D组之间,（P〈0．05）;200倍光镜下,目测计数成纤维细胞,伤后第3、21天,各组别成纤维细胞数量无差异（P〉0．05）,伤后第7、10、14天,A、B组成纤维细胞数量比C、D、E组明显增多（P〈0．001）;通过图像分析检测Smad7平均灰度和平均光密度。Smad7在伤后第3天、第14天表达较强,在C、D组中各时相的表达强于A、B、E组（P〈0．001）,但c组和D组、A组和B组组间比较无差异（P〉0．05）。结论：干扰素γ（IFN—γ）可使新生肉芽组织生长缓慢、成纤维细胞数量减少,延长创面愈合时间,并可使大鼠皮肤创面中Smad7表达增强。     

血管紧张素Ⅱ受体2型对创面愈合过程中微血管形成的影响

目的：观察血管紧张素Ⅱ受体2型（AT2R）在创面肉芽组织微血管形成中的作用,探讨其影响新血管形成的可能机制.方法：用打孔器在小鼠背部制成直径6.0 mm全层皮肤缺损创面模型,将24只C57BL/6J小鼠分成两组（n=12）：PD123319处理组腹腔注射特异性AT2R阻断剂PD123319（10 mg·kg-1·d-1）,对照组腹腔注射等量生理盐水.分别在创面形成后第3、5、7、和14天取创面组织标本,每个时间点3只小鼠.另有6只作为正常对照.采用HE染色观察肉芽组织和新血管形成的情况,应用ELISA法检测创面愈合过程中创面局部组织血管内皮生长因子受体1（VEGFR1）的变化,免疫组织化学方法检测正常小鼠皮肤与创面愈合过程中创面局部组织AT2R的表达情况.结果：正常小鼠皮肤AT2R在整个表皮层均有阳性表达,在真皮层,AT2R主在微血管内皮细胞,皮肤附件如毛囊、汗腺、皮脂腺有阳性表达.在小鼠全层皮肤缺损创面愈合过程中,创面局部组织AT2R产生逐渐增加,第7天达到峰值,以后逐渐下降.在伤后第5天和第7天,对照组创面肉芽组织的面积分别为（9.37±0.53）mm2和（7.15±0.42）mm2,PD123319处理组创面肉芽组织面积分别为（11.51±0.98）mm2和（9.32±0.67）mm2,两组间差异有统计学意义（P〈0.05）.PD123319可随时间的延长明显增加肉芽组织中VEGFR1的表达和血管形成的组织学评分,在第7天达到峰值,两组间差异有显著性（P〈0.05）,然后均逐渐下降.结论：在创面愈合过程中,AT2R可能参与创面的愈合及其后期的塑性改建,并通过调节VEGFR1水平影响肉芽组织中微血管的形成.     

大鼠深Ⅱ度烫伤创面愈合中血管形成与血流变化特点

目的：观察大鼠深Ⅱ度烫伤模型创面愈合中血管形成与血流改变的特点。方法：Wistar大鼠48只,随机分为A、B两组,A组（n=42）：为组织病理观察组,根据实验设计又分伤后即刻、1天、3天、7天、14天及21天及正常对照组,每组6只;B组（n=6）：为血流量检测组。在实验大鼠背部制作深Ⅱ度烫伤模型,A组大鼠在各时间点活杀取材,进行病理和免疫组化检测;B组大鼠连续检测背部同一部位正常皮肤及伤后各时间点的创面血流量。结果：烫伤大鼠伤后3～7天,肉芽组织内出现单个的不成腔的血管内皮细胞,数目随肉芽组织的增多而逐渐增加,后逐渐形成管腔;伤后14天,肉芽组织内有腔毛细血管进一步增多,已出现结构较完整的成熟小血管;伤后21天血管形态和数量已接近正常皮肤。深Ⅱ度烫伤大鼠伤后即刻,皮肤血流量锐减为正常皮肤血流量的51％;伤后3天时,创面血流量仅迭正常血流量的68％;至伤后14天,创面血流量升到正常值的88％;14天后逐渐正常。结论：在皮肤深Ⅱ度烫伤创面愈合过程中,随着肉芽组织内内皮细胞数量和结构的变化,创面的血流量不断增加,前者的变化是后者变化的基础。     

纳米微囊-VEGF复合体转染对慢性创面愈合影响的研究

目的：研究纳米微囊-VEGF复合体转染对慢性创面愈合的影响。方法：以VEGF为目的基因，构建真核表达载体pcDNA3．1／myc—hisA—VEGF165，纳米微囊包裹后作用于兔耳慢性创面，于术后14天通过创面观察以及组织学染色、显微测量，观察其对创面的影响。结果：转基因组创面肉芽生长及上皮爬行速度明显快于慢性创面组；HE染色转基因组肉芽组织中大量的成纤维细胞聚集，微血管数量增多；新生上皮生长NEG在非缺血创面组最高，慢性创面组最低，其中前者较后者增加249％，而转基因组较慢性创面组增加了165％；肉芽组织厚度PH转基因组较慢性创面组增加了70％，而非缺血创面组较慢性创面组增加了46％；肉芽组织体积NGTV在转基因组及非缺血创面组与慢性创面组比较，分别增加了317％、302％。结论：非病毒载体纳米微囊-VEGF复合体能明显促进慢性创面愈合。     

封闭负压引流技术对失感觉神经支配创伤愈合中Bcl-2与NGF/NGF mRNA表达的影响

目的　研究封闭负压引流技术 (vacuum assistedclosure ,VAC)对失感觉神经支配的创面愈合过程中Bcl 2与NGF表达的影响。方法　将 80只SD大鼠随机分成四组 (每组 2 0只 ) ,即实验组(T组 ) :施加VAC的失去神经支配创面 ;对照组 1(C1) :未施加VAC的失去神经支配的创面 ;对照组2 (C2 ) :施加VAC的正常神经支配的创面 ;对照组 3(C3) :未施加VAC的正常神经支配的创面。T、C2组施加间断性VAC每日 3次 ,负压 80mmHg。伤后 1、3、6、9、12d ,四组同时取材 ,采用免疫组化和原位杂交检测各组各时间点Bcl 2与NGF/NGFmRNA表达。结果　在伤后C2组、C3组Bcl 2与NGF/NGFmRNA表达明显 ,水平逐渐升高 ,至第 9天达最高 ,然后降低 ,C2组较C3组Bcl 2和NGF/NGFmRNA维持相对高的状态 (P <0 .0 5 )。T、C1组创缘和肉芽组织中Bcl 2与NGF/NGFmRNA表达相对C2、C3组处于较低水平 (P <0 .0 5 )。结论　VAC通过增强创面组织抑制凋亡相关基因蛋白的表达 ,影响内源性NGF表达 ,具有明显的促进创面愈合的作用。     

不同暂时性关腹材料对腹腔开放后创面愈合影响的研究

目的 观察腹腔开放后腹腔创面愈合的基本过程以及观察不同暂时性关腹材料对于愈合过程的影响。方法 选择24只健康SD雌性大鼠,随机分成四组：A组,单纯聚乙烯片临时关腹;B组,单纯聚丙烯网片临时关腹;C组,聚丙烯网片临时关腹外用生长激素;D组,聚丙烯网片临时关腹外用成纤维细胞生长因子。于腹腔开放后7d取创面肉芽,作病理组织学观察、肉芽微血管密度（MVD）计数、肉芽组织厚度及肉芽成纤维细胞数目比较。结果 各组创面愈合均良好,但聚丙烯网片关腹外用成纤维细胞生长因子组创面肉芽厚度、肉芽内微血管密度（MVP）及成纤维细胞数目都优于其他三组（P值均<0.05）。结论 聚丙烯网片应用于腹腔开放病人,可促进开放处肉芽组织的生长。局部加用生长激素和碱性成纤维细胞生长因子,可进一步加速创面的愈合,其中以聚丙烯网片外用成纤维细胞生长因子效果最好。     

成纤维细胞生长因子促进放烧复合伤创面愈合的实验研究

采用重组的碱性成纤维细胞生长因子(bFGF),观察其对大鼠重度放烧复合伤皮肤创面愈合的作用。结果提示:bFGF治疗组第60天创面完全愈合的百分率较对照组提高28.5％,50％烧伤面积愈合所需的平均时间较对照组提前9天。病理学检查发现,bFGF可刺激成纤维细胞增殖及胶原合成,促进毛细血管增生和肉芽组织形成。在早期,bFGF尚可增强创面炎症反应,提高机体白细胞吞噬功能,加速脾细胞NK活性的恢复。     

失神经支配大鼠皮肤切割创面愈合过程中修复细胞增生活性的研究

目的:研究大鼠失神经支配皮肤切割伤愈合过程中修复细胞增生活性的变化。方法:40只SD大鼠随机分成T、C两组(每组20只),在其背部形成全层皮肤切割伤缺损创面,其中T组为手术损伤鼠T11～L12脊神经皮肤切割伤组,C组为正常有神经支配的皮肤切割伤组,在伤后1、2、3、4周,观察创面愈合,A、B两组同时取材,采用免疫组化和银染法,检测创面修复细胞PCNA的表达和AgNORs颗粒数的变化。结果:T组较C组创面愈合明显延迟,同时修复细胞PCNA表达明显减弱,细胞核内AgNORs颗粒数明显减少,第3周两组的创面PCNA标记指数和AgNORs计数分别为2.11%/18.1%(P=0.001),1.1/3.1个/细胞(P<0.05)。结论:大鼠失神经支配皮肤切割伤愈合较正常创面愈合明显延迟,修复细胞增殖活性明显降低。     

不同剂量龙血生肌温敏凝胶对失神经支配创面促愈合的实验研究

目的:观察应用不同剂量的龙血生肌温敏凝胶对大鼠失神经支配创面促愈合的影响,明确最佳剂量。方法:健康SD大鼠80只,建立失神经支配创面动物模型,随机分成4组,高剂量组、中剂量组、低剂量组、对照组各20只,高、中、低剂量组分别用相应剂量(0.8、0.4、0.2 g/mL)的龙血生肌温敏凝胶,对照组使用凡士林纱布外敷创面,观察创面愈合的大体情况,计算创面愈合所需的时间及其愈合率,采用HE染色检测各时间点创面组织切片的成纤维细胞数量。结果:高、中、低剂量组及对照组创缘皮肤血供均良好,无明显红肿发炎及坏死征兆;创面愈合时间及愈合率对比,高剂量组及中剂量组相近,均比低剂量组及对照组优(P 0.05),而低剂量组又比对照组愈合快(P 0.05)。高中低剂量组的成纤维细胞数量在5个时间点均比对照组显著增多(P 0.05),高、中剂量组的成纤维细胞数量在造模后第11天比低剂量组显著增多(P 0.05)。结论:龙血生肌温敏凝胶对失神经支配创面有促愈合作用,中高剂量的龙血生肌温敏凝胶疗效最佳。     

Wound healing in denervated rat skin

Recently, several reports have suggested that innervation influences wound healing. However, some investigators have reported that nerve injury prevented wound healing while others have suggested it had no influence on full-thickness skin wound healing. We created denervated skin areas on rats by dissection of the spinal hemicord. Subsequently, 15-mm-diameter skin defects were made symmetrically within the denervated area on the right side of the back and the normal innervated area on the left side. Biopsies were performed at 3, 7, and 14 days after wounding. We measured changes of the wound surface area, the rate of wound contraction, and the rate of epithelialization. The differences were not significant at 3 or 7 days after the operation. However, we could observe significantly delayed wound healing of the denervated skin areas compared to the normal areas at 14 days. Both wound contraction and epithelialization were delayed in the denervated groups. Our results suggest that sensory disturbance is a negative factor for skin wound healing.     

Sympathetic denervation accelerates wound contraction but delays reepithelialization in rats

Participation of the peripheral nervous system in wound healing is not well understood. The aim of this study was to investigate the effects of sympathetic denervation on rat excisional cutaneous wound healing. Male rats were chemically denervated with intraperitoneal administration of 6-hydroxydopamine (6-OHDA) in 1% ascorbic acid. 6-OHDA or vehicle was administered twice a week until euthanasia, beginning 7 days before wounding. A full-thickness excisional lesion was performed and the lesion area measured to evaluate wound contraction. After euthanasia, the lesion and adjacent normal skin were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin and eosin or toluidine blue, or immunostained for alpha-smooth muscle actin. Animals treated with 6-OHDA showed acceleration in wound contraction, increase in myofibroblastic differentiation, reduction in mast cell migration, and a delay in reepithelialization. To investigate the effects of neurogenic inflammation, a group of animals was treated with 6-OHDA only after the acute inflammatory phase, and these animals showed delayed wound contraction 3 and 7 days after wounding when compared to those treated before the lesion. In conclusion, the present study shows that sympathetic denervation affects cutaneous wound healing, probably by a decrease in neurogenic inflammation during the initial phase of healing and the absence of catecholamines throughout the final phase.     

Fibroblast subpopulations in intra-oral wound healing

The objective of this study was to characterize fibroblasts at sequential time points during intra-oral wound healing in the rat. Experimental wounds were made at several time points in the mucoperiosteum of the palate of 35-day-old Wistar rats. Fibroblasts were cultured from the biopsies under standard conditions for the same number of passages. The expression of the integrin subunits alpha 1, alpha 6, and beta 1; and the intermediate filaments alpha-smooth muscle actin and vimentin were analyzed by flow cytometry. Western blot analysis was performed at 0, 8, and 60 days postwounding to confirm the expression of both intermediate filaments. The phenotypic profiles of fibroblasts cultured from subsequent stages in the wound healing process differed considerably. We conclude that distinct fibroblast phenotypes can be isolated from different stages in wound healing. These phenotypes remained stable during in vitro culturing. In addition, cryosections of the wound areas were made at identical time points and were immunohistochemically stained for the same antigens. The immunohistochemical staining correlated well to the flow-cytometric data. These results suggest the occurrence of multiple subpopulations of fibroblasts with a specialized function during wound healing. We hypothesize that undesirable consequences of wound healing might be prevented through the modulation of specific fibroblast subpopulations.     

Ⅰ-型胰岛素样生长因子基因转移对烫伤大鼠创面愈合作用的实验研究

目的探讨Ⅰ-型胰岛素样生长因子（insulin-like growth factor Ⅰ，IGF-Ⅰ）基因转移对烫伤大鼠创面愈合的作用效果。方法利用我们成功构建的重组真核表达质粒pcDNA3．1／IGF-Ⅰ，通过脂质体介导转染烫伤大鼠皮肤组织，用免疫组化方法检测IGF-Ⅰ基因在皮肤及肝脏组织的表达情况，观察烫伤大鼠体重、刨面愈合情况等指标。结果免疫组化结果显示，脂质体介导的IGF—Ⅰ基因转移可在创面注射点周围皮肤成纤维细胞中出现阳性表达，而肝脏组织中未出现阳性表达，实验组大鼠创面注射IGF-Ⅰ重组质粒后，创面愈合与对照组比较差异有统计学意义（P〈0．05），实验组大鼠体重与对照组大鼠比较未出现减轻现象（P〈0．05）。结论脂质体介导IGF-Ⅰ基因转移，可促进创面愈合，并可避免IGF-Ⅰ全身应用所带来的副作用。     

Effects of sevoflurane on collagen production and growth factor expression in rats with an excision wound

Background: Sevoflurane is a widely used inhalation anesthetic, but there are no studies on its effect on the wound‐healing process. This study was undertaken to evaluate the effect of exposure time to sevoflurane on wound healing. Method: Male Sprague–Dawley rats were used. Two circular full‐thickness skin defects 8 mm in diameter were made on the dorsum of the rats. The animals were divided into six groups according to exposed gas type and time: S1 (sevoflurane, 1 h), S4 (sevoflurane, 4 h), S8 (sevoflurane, 8 h), O1 (oxygen, 1 h), O4 (oxygen, 4 h), and O8 (oxygen, 8 h). The surface area of the wounds was measured 0, 1, 3, and 7 days after surgery. Separately, the mean blood pressures (MBP) and arterial oxygen pressures (PaO₂) were monitored during the sevoflurane exposure. Collagen type I production and transforming growth factor‐β1 (TGF‐β1) and basic fibroblast growth factor (bFGF) expression on the wound surface were analyzed. Routine histological analysis was also performed. Result: Exposure duration to sevoflurane had no influence on MBP and PaO₂. The reduction in wound size and collagen type I production was delayed in S8. The expression of TGF‐β1 and bFGF on the wound surface in S8 was significantly attenuated in S8. The histology of the S8 demonstrated a delayed healing status. Conclusions: Prolonged exposure to sevoflurane might alter the inflammatory phase of the wound‐healing process by attenuation of growth factor expression such as TGF‐β1 and bFGF and subsequently by reduced collagen production.     

Significance of T-lymphocytes in wound healing

To determine the importance of T-lymphocytes in wound healing, we examined the effect of T-lymphocyte depletion on the healing of surgical wounds. Thirty Balb/c mice were injected intraperitoneally with 1 mg of rat anti-mouse (IgG2b) cytotoxic monoclonal antibody (30H12) against the Thy1.2 (all T) determinant. Twenty-four hours later animals showed a greater than 95% depletion of Thy1.2 cells in peripheral blood and spleen. Thirty control mice received nonspecific rat immunoglobulin (1 mg). Twenty-four hours after treatment mice underwent a 2.5 cm dorsal skin incision with subcutaneous placement of polyvinyl alcohol sponges. Injections were repeated at weekly intervals. Wound healing was assessed at 2, 3, and 4 weeks by the breaking strength of wound strips and by the hydroxyproline content of sponge granulomas (an index of wound reparative collagen deposition). Thy1.2 depletion at death was 95% to 57% in peripheral blood and 86% to 68% in the spleen. Both groups gained weight equally. We found that T cell depletion significantly impairs wound breaking strength and wound collagen deposition at all times studied. The data strongly suggest that T-lymphocytes modulate fibroblast activity during normal wound healing.     

I-型胰岛素样生长因子基因转移对烫伤大鼠创面愈合作用的实验研究

目的探讨I-型胰岛素样生长因子(insulin-likegrowthfactorI,IGF-I)基因转移对烫伤大鼠创面愈合的作用效果。方法利用我们成功构建的重组真核表达质粒pcDNA3.1/IGF-I,通过脂质体介导转染烫伤大鼠皮肤组织,用免疫组化方法检测IGF-I基因在皮肤及肝脏组织的表达情况,观察烫伤大鼠体重、创面愈合情况等指标。结果免疫组化结果显示,脂质体介导的IGF-I基因转移可在创面注射点周围皮肤成纤维细胞中出现阳性表达,而肝脏组织中未出现阳性表达,实验组大鼠创面注射IGF-I重组质粒后,创面愈合与对照组比较差异有统计学意义(P<0.05),实验组大鼠体重与对照组大鼠比较未出现减轻现象(P<0.05)。结论脂质体介导IGF-I基因转移,可促进创面愈合,并可避免IGF-I全身应用所带来的副作用。     

创面愈合组织三种生长相关因子表达及信号转导机制的实验研究

目的探讨烫伤后创面组织中生长相关因子c-fos、c-myc和bFGF表达的变化规律以及c-fos在伤后皮肤创面愈合过程中的调控作用,研究蛋白激酶C通路对上述因子表达的影响.方法大鼠188只,制成30%深Ⅱ度烫伤模型,随机分为正常对照组(8只)、单纯烫伤组、c-fos抗体处理组、bFGF治疗组、蛋白激酶C通路抑制剂(H7)组以及蛋白激酶C通路激活剂二乙酰一肟组(各36只).采用原位杂交、逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法检测创面组织c-fos、c-myc与bFGF基因及蛋白表达规律.结果(1)烫伤诱导c-fos表达增加在前,其次是bFGF,最后是c-myc,分别于伤后3h、1d以及3d到达面密度峰值(14.5±1.3,t=13.306;0.15±0.04,t=3.460和0.11±0.05,t=2.292;与单纯烫伤组比较均P＜0.05).(2)应用外源性c-fos抗体减少创面组织3种因子的表达,其中c-myc与bFGF基因表达量分别下降80%和85%.(3)?H7明显抑制?c-fos?与?bFGF?基因及蛋白的表达,而使?c-myc?基因及蛋白的表达高峰时间延迟至伤后?6h;?二乙酰一肟作用与?H7?相反,?它可以使c-myc表达高峰提前至伤后6h,同时使c-fos与bFGF表达量分别增加至0.23±0.07(t=2.942)和0.69±0.07(t=5.134,与单纯烫伤组比较均P＜0.01).结论烫伤可以激活3种生长相关因子基因和蛋白的表达;c-fos在创面愈合过程中具有重要调控作用;蛋白激酶C通路在创面修复的信号传导中具有重要作用.     

Insulin treatment ameliorates impaired corneal reepithelialization in diabetic rats

Patients with diabetes are at an increased risk for developing corneal disorders, often as a result of surgical and nonsurgical trauma. This study investigated whether intensive treatment of diabetes with the goal of maintaining blood glucose concentrations close to the normal range could ameliorate the delayed corneal wound healing found in animals with uncontrolled diabetes. Diabetes was induced with streptozotocin, and rats were divided into groups based on the degree of blood glucose control: 1) not treated with insulin implants (DB group), 2) receiving insulin implants and determined to be normoglycemic (DB-IN group), and 3) normal, nondiabetic animals serving as controls. Immediately before wounding at 9 or 11 weeks after the induction of the diabetic state, corneal thickness and corneal sensitivity of the DB and DB-IN groups were comparable with controls. DB, but not DB-IN, rats exhibited subnormal intraocular pressure. At 9 and 11 weeks after the onset of diabetes, the corneas of the right and left eyes, respectively, were abraded by mechanical scraping. The DB rats had residual corneal epithelial defects that ranged from 23% to 5.6-fold larger compared with the control group and a rate of healing that was 19% slower than control animals. The DB-IN group had healing characteristics similar to the control group. DNA synthesis in the peripheral cornea and conjunctiva, but not the limbus, of DB animals was reduced 50 and 91%, respectively, from control levels. Cell proliferation in the DB-IN group was comparable with the control group, with the exception of a 72% increase in the peripheral cornea in the DB-IN group. These results indicate that intensive therapy with insulin, which establishes normoglycemia in rats with diabetes, prevents the delay in wound healing of ocular surface epithelium observed in poorly controlled diabetic animals.