逆转录病毒介导的E1A激活基因阻遏子抑制大鼠颈动脉球囊损伤后新生内膜形成

目的:探讨逆转录病毒介导的E1A激活基因阻遇子(CREG)过表达对球囊损伤后大鼠颈动脉新生内膜形成的影响。方法:以球囊拉伤法制备大鼠颈动脉损伤模型,应用Pluronic F127胶分别包裹含有pLNCX/CREG、pLNCX/GFP载体的逆转录病毒,并于损伤即刻涂抹于血管外壁。随后在损伤不同时点取出损伤动脉,测量内膜面积及内膜/中膜面积比。用免疫组织化学法观察CREG、SMα-actin及Ki-67变化,Western blotting检测CREG蛋白表达。结果:血管损伤后2 d pLNCX/GFP组血管中膜平滑肌层GFP表达。pLNCX/CREG组大鼠血管CREG表达明显多于单纯损伤组。感染CREG组大鼠球囊损伤后血管新生内膜的形成明显受抑,Ki-67蛋白表达明显少于、而SMα-actin表达则明显多于单纯损伤组。结论:CREG过表达能抑制血管损伤后平滑肌细胞的增殖并促进其分化,提示调控CREG基因的表达可能为预防PCI术后再狭窄提供有效手段。     

The effect of quercetin on neointima formation in a rat artery balloon injury model

This study aimed at investigating the effect of quercetin on neointima hyperplasia in the abdominal aorta of rats after balloon injury and expressions of related growth factors. Fifty-four healthy male Sprague-Dawley rats were randomly divided into five groups: a sham-operation group (sham, n=6), a control group (control, n=12), and three quercetin-treated groups: Q50 group (50 mg/kg body weight/day, n=12), Q100 group (100 mg/kg body weight/day, n=12), and Q200 group (200 mg/kg body weight/day, n=12) 3 days before balloon injury until the end of the experiment. Fourteen days after injury, rats were killed, and the abdominal aortas were harvested. Hematoxylin–eosin staining showed that quercetin significantly reduced the neointimal areas and the intimal to medial ratio in the Q100 and Q200 groups 14 days after injury. Immunohistochemical analysis showed that quercetin significantly inhibited PCNA, PDGF-BB, b-FGF, and TGF-β1 expressions in the neointima. Masson's trichrome showed that quercetin significantly reduced collagen deposition in the neointima. We concluded that quercetin significantly inhibited neointimal hyperplasia in rat abdominal aorta 14 days after injury in relatively high doses. This effect of quercetin might be partially attributed to the suppression of PDGF-BB, b-FGF, and TGF-β1 expressions.     

Highly active antiretroviral therapy attenuates re-endothelialization and alters neointima formation in the rat carotid artery after balloon injury

Highly active antiretroviral therapy (HAART) has led to a sustained decline of HIV-associated morbidity and mortality. HAART exhibits significant side effects, however, such as hyperlipidemia and hyperglycemia, which possibly contribute to accelerated atherosclerosis in HAART-treated patients. In addition, direct effects of HAART on vascular cells have been described, which may promote atherosclerotic lesion formation. The effects of HAART on balloon-induced neointima formation have not been studied previously. The rat carotid artery balloon model was used to evaluate the effects of HAART (lopinavir, ritonavir, lamivudine, and zidovudine) on neointima formation and endothelial recovery. Furthermore, the effects of concomitant administration of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor rosuvastatin were investigated. HAART-treated animals displayed an increase in lesion size (neointima/media ratio: 1.14 +/- 0.32 vs. 1.31 +/- 0.20 in control vs. HAART; P < 0.05) and an impaired regenerative capacity of the endothelium, as indicated by reduction in endothelial regrowth from an adjacent undilated vessel segment 14 days after injury (re-endothelialization area: 8.29 +/- 1.45 mm vs. 5.09 +/- 0.53 mm in control vs. HAART; P < 0.05). When rosuvastatin was given in addition to HAART, these effects were not observed. In conclusion, HAART inhibited endothelial cell-mediated healing and promoted neointima formation after angioplasty in rats. These deleterious effects were attenuated by cotreatment with rosuvastatin, however. Our studies suggest that currently used drug regimens against HIV infection may lead to an increased risk for restenosis after percutaneous vascular interventions. Moreover, the findings indicate that the additional treatment with statins might counteract these adverse effects by HAART.     

Angiographic evaluation of the rat carotid balloon injury model

Rationale

The rat carotid balloon-injury (BI) model is a widely used model of intimal hyperplasia (IH) and vascular remodeling. A variable degree of IH after BI has been previously reported, and we have encountered technical challenges and suboptimal results with the original method.

Objective

To evaluate the original rat carotid artery BI method with the use of micro-angiography. We tested the hypothesis that in order to obtain an optimal arterial response, BI should be limited to the common carotid artery with preservation of blood flow.

Methods and results

The left common carotid artery (CCA) was injured by one of three different methods. Carotid angiograms and pathology were examined 14 days after BI.A 2 F Fogarty balloon catheter inflated to 2 atm inside the aortic arch would not slide back into the common carotid artery until deflation to 0.5 to 0.7 atm. Four out of five (80%) vessels injured with this method developed excessive inflammation without discernible IH. Six out of nine (66%) arteries that underwent BI limited to the CCA at 2 atm developed the largest angiographic stenosis (p = 0.003) and IH (0.20 ± 0.03 mm², p = 0.028). Ten out of eleven (91%) arteries injured with a variable pressure of 1.5 to 2.2 atm, based on the operator's feedback, developed considerable IH (0.12 ± 0.02 mm²). All injured carotid arteries with preserved blood flow on angiography developed IH with intact histological boundaries.

Conclusions

Optimal IH with preservation of histological boundaries is achieved by graded BI limited to the CCA that preserves carotid blood flow.     

Optimized polymeric film-based nitric oxide delivery inhibits bacterial growth in a mouse burn wound model

Nitric oxide (NO) has many biological roles (e.g. antimicrobial agent, promoter of angiogenesis, prevention of platelet activation) that make NO releasing materials desirable for a variety of biomedical applications. Localized NO release can be achieved from biomedical grade polymers doped with diazeniumdiolated dibutylhexanediamine (DBHD/N₂O₂) and poly(lactic-co-glycolic acid) (PLGA). In this study, the optimization of this chemistry to create film/patches that can be used to decrease microbial infection at wound sites is examined. Two polyurethanes with different water uptakes (Tecoflex SG-80A (6.2 ± 0.7 wt.%) and Tecophilic SP-60D-20 (22.5 ± 1.1 wt.%)) were doped with 25 wt.% DBHD/N₂O₂ and 10 wt.% of PLGA with various hydrolysis rates. Films prepared with the polymer that has the higher water uptake (SP-60D-20) were found to have higher NO release and for a longer duration than the polyurethane with the lower water uptake (SG-80A). The more hydrophilic polymer enhances the hydrolysis rate of the PLGA additive, thereby providing a more acidic environment that increases the rate of NO release from the NO donor. The optimal NO releasing and control SG-80A patches were then applied to scald burn wounds that were infected with Acinetobacter baumannii. The NO released from these patches applied to the wounds is shown to significantly reduce the A. baumannii infection after 24 h (∼4 log reduction). The NO release patches are also able to reduce the level of transforming growth factor-β in comparison to controls, which can enhance re-epithelialization, decrease scarring and reduce migration of bacteria. The combined DBHD/N₂O₂ and PLGA-doped polymer patches, which could be replaced periodically throughout the wound healing process, demonstrate the potential to reduce risk of bacterial infection and promote the overall wound healing process.     

Protective effect of hydrogen sulfide on balloon injury-induced neointima hyperplasia in rat carotid arteries

Endogenous hydrogen sulfide (H(2)S), generated from homocysteine metabolism mainly catalyzed by cystathionine gamma-lyase (CSE), possesses important functions in the cardiovascular system. In this study, we investigated the role of H(2)S during the pathogenesis of neointimal formation induced by balloon injury in rats. CSE mRNA levels were reduced by 86.5% at 1 week and 64.0% at 4 weeks after balloon injury compared with the uninjured controls. CSE activity was also correspondingly reduced. Endogenous production of H(2)S in the injured carotid artery was significantly inhibited at 1 week and 4 weeks after balloon injury. Treatment with NaHS (a donor of H(2)S) enhanced methacholine-induced vasorelaxation of balloon-injured artery. More importantly, treatment with NaHS significantly inhibited neointima formation (0.15 +/- 0.01 mm(2) versus 0.21 +/- 0.01 mm(2), P < 0.001) of the balloon-injured carotid arteries and reduced the intima/media ratio (1.05 +/- 0.07 versus 1.43 +/- 0.06, P < 0.001). A significant decrease in vascular smooth muscle cell proliferation was demonstrated by bromodeoxyuridine incorporation at day 7 after injury. In conclusion, CSE expression and H(2)S production are reduced during the development of balloon injury-induced neointimal hyperplasia, and treatment with NaHS significantly reduces neointimal lesion formation.     

一氧化氮合酶在新生鼠肠损伤中的作用

目的建立新生鼠肠损伤模型,探讨不同类型一氧化氮合酶在其发生发展中的作用.方法新生鼠随机分为对照组8只,实验组每一时相点各8只.将E coli O55:B5脂多糖5mg/kg注入新生鼠胃内,分别于注入后3h、6h、12h、24h处死动物,分离胃肠道.取部分回肠末端组织固定,包埋切片,常规HE染色,光镜下观察其组织学改变,进行损伤评分.其余回肠组织用于测定原生型一氧化氮合酶(constitutive nitric oxide synthase, cNOS)和诱生型一氧化氮合酶(inducible nitric oxide synthase, iNOS)活性,并分别与组织学评分进行相关性分析.结果实验组3h、6h、12h、24h损伤评分分别为(1.54±0.87)、(1.79±0.75)、(1.92±0.43)、(2.29±0.60),均明显高于对照组(0.08±0.15)(P<0.05); 6h、24hcNOS活性分别为(34.28±7.34)、(22.96±2.93) nmol/gprot/min,显著低于对照组(47.59±14.55) nmol/gprot/min (P<0.05).6h iNOS活性(6.73±2.40) nmol/gprot/min,显著低于对照组(10.27±3.36) nmol/gprot/min(P<0.05).实验组24h内回肠组织cNOS活性与其平均损伤程度呈显著负相关(P<0.001);iNOS活性与损伤程度无显著相关性(P>0.05).结论 cNOS和iNOS在新生鼠肠损伤中作用不同,因此治疗新生儿坏死性小肠结肠炎时应慎重选择NOS抑制剂.     

Local delivery of nitric oxide from an eluting stent to inhibit neointimal thickening in a porcine coronary injury model

To assess the effect of a NO-eluting stent on reducing neointimal thickening in a porcine coronary artery stent injury model, sodium nitroprusside (SNP), a NO donor, was incorporated into polyurethane (PU) polymer and coated onto metallic coil stents, and two types of stents with thin and thick barrier coatings were characterized. In vivo biological activity of the NO-eluting stents was assessed by measurement of coronary arterial cGMP levels in 32 pigs/64 arteries at days 1, 2, 7 and 14. Morphometric analyses were performed in 16 pigs to determine the effect of NO-eluting stents on neointimal hyperplasia 28 days following arterial injury. The SNP-coated stents released NO in a controlled manner for up to 4 weeks in the in vitro experiments and an increase in local tissue cGMP levels was demonstrated for up to 14 days. The neointimal area at 28 days was not diminished, however, by NO eluded from either stents of thin or thick barriers (control bare stent - 0.66 mm2, control PU stent - 0.68 mm2, SNP-PU thin coating stent - 0.78 mm2, SNP-PU thick coating stent - 0.85 mm2; all p=NS). In conclusion, the SNP-coated polymer stent exerted a local biological effect on the arterial wall, with sustained elevation of cGMP level. Although local delivery of NO from this device did not reduce neointimal hyperplasia in this porcine model, this polymer-coated stent might be a promising tool for administration of other agents that may modify the reparative tissue responses leading to restenosis.     

反义凝血酶受体基因表达抑制大鼠动脉内膜损伤后内膜增生

目的 了解凝血酶及其受体在血管损伤后动脉内膜增生中的作用,以进一步阐明经皮冠状动脉血管腔内成形术（PTCA）后再狭窄的发生机制,为寻找再狭窄的防治途径提供线索。方法 采用球囊导管损伤动脉内膜的方法建立大鼠颈动脉球囊损伤模型。用纳米粒子包装凝血酶受体重组反义基因质凿pLXSN/ATR,用保护灌注的方法局部定位转染损伤后的大鼠颈动脉。结果 PCR检测发现重组基因整合,RNA斑点杂交观察到实验组大鼠颈动脉壁内有重组反义凝血酶受体基因表达,正义凝血酶受体基因的表达受到明显抑制,反义基因转染组新生内膜,中膜比例降低了40．9％。结论 反义凝因酶受体重组基因转基因表达对大鼠颈动脉球囊损伤后动脉内膜的增生具有抑制作用,提示凝血酶及其受体在PTCA后再狭窄过程中有重要作用,为再狭窄的防治提供了新的线索。     

Ultrastructural localisation of nitric oxide synthase, endothelin and binding sites of lectin (from Bandeirea simplicifolia) in the rat carotid artery after balloon catheter injury

An immunocytochemical and cytochemical study has been made on the ultrastructural localisation of type III (endothelial) nitric oxide synthase, endothelin-1 and the binding sites of lectin from Bandeirea simplicifolia to the endothelium surface-associated glycoproteins in the rat left common carotid artery at 1 and 28 d after Fogarty embolectomy balloon catheter-induced injury. Controls were carotid arteries from sham operated rats. In the controls, the immunoreactivity to nitric oxide synthase-III and endothelin-1 was localised in different proportions in vascular endothelial cells (36·9%±4·3 and 7·6%±2·7, respectively); immunoreactivity was confined to the cytoplasm and the membranes of intracellular organelles and structures. In contrast, staining with lectin was localised on the luminal surface of all endothelial cells. 1 d after injury, platelets were adherent to the endothelium-denuded intima. Some of the platelets displayed immunoreactivity to nitric oxide synthase-III and endothelin-1 and were stained with lectin. 28 d after injury, a neointimal thickening of substantial size was present. Subpopulations of the regrown endothelial cells covering the luminal surface of the neointima showed positive immunoreactivity to nitric oxide synthase-III and endothelin-1 but there was a significant decrease in the proportion of nitric oxide synthase-III-containing endothelial cells (17·2%±1·9; P < 0·001) and a significant increase in the proportion of endothelin-1-containing endothelial cells (36·9%±4·7; P < 0·001) compared with the controls. Staining with lectin was associated with the cell membrane of all endothelial cells and in addition with cells located ‘deeper’ in the neointima which showed lectin-positive plasmalemma, Golgi complex and multivesicular bodies/lysosomes. In conclusion, regenerated endothelial cells of the neointima showed reduced population (2–fold) of nitric oxide synthase-III- and increased population (5–fold) endothelin-1-positive cells. The subendothelial location of some lectin-stained cells after balloon catheter injury indicates the heterogeneity of the neointima and suggests that some of these cells are involved in early angiogenesis. 24 h and 28 d after injury some platelets showed positive immunoreactivity for nitric oxide synthase-III and endothelin-1.     

内皮型一氧化氮合酶基因转染对血管损伤后新生内膜增生的影响

背景：一氧化氮能够抑制血管平滑肌细胞的迁移和增殖,而一氧化氮合酶是其合成的关键酶,有关一氧化氮合酶基因体内转染对平滑肌细胞及动脉粥样硬化血管损伤后内膜增生影响少有报道。 目的：观察内皮型一氧化氮合酶 (endothelial nitric oxide synthase,eNOS)基因体内局部转染对动脉粥样硬化大鼠血管损伤后新生内膜增生的抑制作用。 方法：建立动脉粥样硬化Wistar大鼠颈动脉球囊损伤模型,建模后随机分成空白对照组、AdCMV-lacz对照组和AdCMV-eNOS组,分别将PBS,AdCMV-lacz和AdCMV-eNOS体内转染至以上3组大鼠的损伤血管壁。转染2周后培养并鉴定损伤局部平滑肌细胞,并用RT-PCR法检测各组损伤及转染后血管平滑肌细胞eNOS mRNA的表达,同时观察转染后不同时期新生内膜增生的影响。 结果与结论：AdCMV-eNOS组的颈总动脉血管平滑肌细胞可表达eNOS mRNA。3组大鼠转染后1和3个月,AdCMV-eNOS组内膜/中膜面积比值低于空白对照组和AdCMV-lacz对照组(P < 0.01)。结果显示,eNOS基因体内转染损伤后血管可以抑制血管新生内膜增生,减少再狭窄发生率。     

KLF4抑制球囊损伤诱导的新生内膜形成

目的： 通过腺病毒载体介导外源性KLF4在大鼠颈动脉球囊剥脱血管中进行表达,观察新生内膜增生情况,研究外源性KLF4对球囊损伤诱导的新生内膜形成的影响及初步探讨其机制。方法： 构建含有KLF4基因的重组腺病毒载体pAd-KLF4,将其导入内皮剥脱的血管壁。用HE染色观察血管新生内膜的厚度,免疫组织化学染色和RT-PCR分别检测外源性KLF4在血管中的表达以及与增殖和分化标志基因表达的关系。结果： 重组腺病毒pAd-KLF4可在血管壁中稳定表达KLF4。KLF4的过表达可显著抑制球囊损伤后血管新生内膜的增厚,转染pAd-KLF4的血管,其内膜/中膜比值（I/M）（0.52±0.15）明显小于pAd对照组（2.48±0.38）,P<0.05。pAd-KLF4组血管壁增殖标志蛋白PCNA和c-Jun表达也较pAd组明显降低（P<0.05）。结论： KLF4过表达可阻断损伤诱导的血管平滑肌细胞表型转化,进而抑制球囊剥脱后血管内膜的增生。     

青白散对慢性软组织损伤模型大鼠骨骼肌一氧化氮合酶系统和一氧化氮的影响

背景：对慢性软组织损伤后一氧化氮合酶系统和一氧化氮的研究目前较少。 目的：观察青白散对大鼠慢性软组织损伤模型骨骼肌中一氧化氮合酶系统和一氧化氮的影响。 方法：雄性 SD 大鼠随机分为对照组、模型组、氨基胍组、青白散组。后3组采用机械损伤法制备慢性骨骼肌损伤动物模型,分别予以生理盐水 10 mL/kg,0.10 g/kg氨基胍,0.54 g/kg青白散,1次/d,连续 14 d。于给药后1,2,3周,分别检测大鼠肌组织一氧化氮含量、总一氧化氮合酶和诱导型一氧化氮合酶的活性。 结果与结论：骨骼肌损伤修复过程中,模型组大鼠骨骼肌中一氧化氮含量、总一氧化氮合酶和诱导型一氧化氮合酶的活性较对照组显著增高;而青白散组和氨基胍组大鼠骨骼肌中一氧化氮含量、总一氧化氮合酶和诱导型一氧化氮合酶的活性均较模型组显著降低。说明青白散可能通过阻抑诱导型一氧化氮合酶诱导过量一氧化氮的产生,为慢性软组织损伤的修复创造了有利条件。     

Acute hypoxia elevates nitric oxide generation in rat carotid body in vitro

In acute hypoxia, the release of nitric oxide (NO) produced in rat carotid body is unclear. The concentration of NO was measured electrochemically with a Pt/Nafion/Pd-IrOx/POAP-modified electrode placed on the surface of isolated carotid bodies superfused with bicarbonate-buffer saline at 35 degrees C. In hypoxia, the concentration of NO in the carotid body was increased by 17+/-2 nM. The amount of NO release during hypoxia was augmented by increasing the number of carotid bodies surrounding the electrode and also in the presence of L-arginine. In addition, the hypoxia-induced elevation of NO was abolished by pretreatment with a nitric oxide synthase (NOS) inhibitor, L-N(G)-nitroarginine methylester (L-NAME). The results suggest that endogenous NO production in the carotid body increases during hypoxia. Electrophysiological measurement of single fiber activity in the sinus nerve revealed that L-NAME treatment enhances the afferent discharge in response to hypoxia. This confirms that the hypoxia-induced elevation of NO suppresses the carotid chemoreceptor response to hypoxia. Taken together, it is concluded that acute hypoxia increases NO generation in the rat carotid body, and that the elevated levels of NO suppress carotid chemoreceptor activity during hypoxia. Hence, NO may play an active inhibitory role in the control of carotid chemoreceptor activity during hypoxia.     

Sodium nitroprusside as a nitric oxide donor in a rat intestinal ischemia-reperfusion model

AIM: The aim of this study was to investigate the efficacy of sodium nitroprusside in the reduction of the intestinal ischemia-reperfusion injury as a nitric oxide donor after intraperitoneal administration. METHODS: The histopathological examinations and tissue malonyldialdehyde levels of 35 Wistar albino rats that were subjected to ischemia-reperfusion, were performed in 5 groups. The groups include Control, Ischemia -reperfusion, Sodium nitroprusside, NG-Nitro-L-Arginine Methyl Ester (L-NAME) and Sodium nitroprusside+L-NAME. Each rat was subjected to ischemia for 40 minutes and reperfusion for 30 minutes, except the control group. The medications were done intraperitoneally as saline 4 ml/kg, Sodium nitroprusside 5 mg/kg, L-NAME 10 mg/kg just before reperfusions. RESULTS: Significant tissue injury in histological sections and an increase in tissue levels of Malonyldialdehyde was detected in the I/R group. The efficacy of intraperitoneal administration of Sodium nitroprusside in both Sodium nitroprusside alone and Sodium nitroprusside+L-NAME groups was found statistically significant for the reducing of injury scores (p<0.05). The difference between the Ischemia/reperfusion and Sodium nitroprusside groups was found statistically significant as in the Ischemia/reperfusion and Sodium nitroprusside+L-NAME groups due to the tissue Malonyldialdehyde levels (p<0.05). There was no statistical difference between Ischemia/reperfusion and L-NAME groups. CONCLUSION: Ischemia/reperfusion induced injury might be reduced by the intraperitoneal administration of Sodium nitroprusside, even in the presence of L-NAME, in the rat intestinal model.     

Inhaled carbon dioxide inhibits lower airway nitric oxide formation in the guinea pig

The present study addressed the effect of inhaled carbon dioxide on lower airway nitric oxide formation in normoxic anaesthetized guinea pigs. Ventilation with carbon dioxide (1.5, 3, 6, 9 and 12%) induced a concentration-dependent decrease in the basal concentration of nitric oxide in exhaled tracheal air. A maximal reduction in exhaled nitric oxide of ≈25% was induced by 12% carbon dioxide in inhaled air. Ventilation with positive end-expiratory pressure (7 cmH₂O) increased the concentration of exhaled nitric oxide. Inhalation of carbon dioxide had a larger, concentration-dependent, inhibitory effect (maximally 60%) on the lower airway nitric oxide formation induced by ventilation with positive end-expiratory pressure, as compared with the effect on the basal concentration of nitric oxide. The results show that inhaled carbon dioxide suppresses lower airway nitric oxide excretion in the guinea pig. Endogenous carbon dioxide might exert effects through regulation of endogenous nitric oxide formation, for example in the regulation of airway tone or in ventilation–perfusion matching.     

生长反应因子与大鼠颈动脉损伤后内膜增生

背景：经皮冠状动脉介入治疗后再狭窄仍是影响介入治疗远期疗效的严重的临床问题。 目的：在大鼠颈动脉球囊损伤模型中,探讨早期生长反应因子诱骗寡脱氧核苷酸对损伤后的血管内膜的影响,并初步探讨其分子机制。 方法：利用2F Fogarty导管损伤Wistar大鼠颈动脉,构建大鼠球囊损伤模型,在转染试剂Fugene 6介导下经血管腔内转染生长反应因子诱骗寡脱氧核苷酸,苏木精-伊红染色法观察血管内膜增生情况,免疫组化法检测Cyclin D1,观察其表达情况。 结果与结论：早期生长反应因子诱骗寡脱氧核苷酸可以显著抑制大鼠颈动脉球囊损伤后血管内膜增生,同时也可以下调大鼠颈动脉球囊损伤后表达显著增加的Cyclin D1。说明生长反应因子诱骗寡脱氧核苷酸可能通过抑制Cyclin D1的表达,使细胞周期停滞,从而抑制损伤后的大鼠颈动脉内膜的增生。     

超声观察大鼠颈总动脉机械损伤模型

目的：用超声指标和病理指标评价大鼠颈总动脉机械损伤模型。方法：建立大鼠颈总动脉内皮剥脱模型,在术后1、7、28d分别超声观察颈总动脉管腔、血流速度、脉动指数(PI)和阻力指数(RI),与病理切片对照。结果：大鼠颈总动脉内皮剥脱后管腔狭窄,血流速度减慢,PI、RI增高,均于损伤第28天达峰值。结论：超声指标能够无创动态观察大鼠颈总动脉损伤及修复过程。