Effects of granulocyte colony-stimulating factor on repair of injured canine arteries

Background Endothelial progenitor cells （EPCs） derived from bone marrow may differentiate into endothelial cells and participate in endothelial repair. These cells can be mobilized into peripheral blood by cytokines, including granulocyte colony-stimulating factor （G-CSF）. In the present study, we investigated the effects of G-CSF on neointimal formation and restenosis in a canine model of arterial balloon injury.
Methods Sixteen male beagle dogs were injected subcutaneously with 20 μg·kg^-1·d^-1 recombinant human G-CSF （n=8） or normal saline （n=8） for 1 week. On the fifth day of treatment, the dogs underwent renal arterial angioplasty. At 8 weeks after arterial balloon injury, angiographic observations were made and injured arteries were processed for morphometric analysis of neointimal formation.
Results Peripheral white blood cell counts were increased by 3.34-fold compared to baseline on the fifth day of administration of G-CSF. Angiographies revealed that one stenosis had occurred among the eight injured renal arteries from dogs treated with G-CSF, whereas all injured renal arteries from dogs treated with normal saline remained patent. The mean extent of stenosis among injured arteries was 18.3%±17.9% in the G-CSF treated group compared to 12.5%±7.6% in the saline treated control group （P=0.10）. G-CSF treatment slightly increased neointimal thickness （0.42±0.15 mm vs 0.25±0.06 mm, P=-0.08） with an intima to media ratio of 0.83±0.49 vs 0.54±0.18 （P=0.11）.
Conclusions G-CSF treatment does not attenuate neointimal hyperplasia and restenosis formation in a canine model of renal arterial injury, suggesting that the therapeutic strategy for preventing restenosis by stem cell mobilization should be investigated further.     

The Role of NF-kB and I-kB in Intimal Proliferation Following Balloon Catheter-induced Injury in the Rat Carotid Artery

The aim of our study was to gain insight into the molecular and cellular mechanisms of post-angioplasty restenosis using balloon catheter-induced injury model in the rat carotid artery. SD rats were subjected balloon catheterization at one side carotid artery as study group and another side as control group. Six rats were killed on the 6 h, and 3rd, 7th, 14th, 28th day after balloon-induced injury respectively. The intimal thickness and the expression of NF-κB and I-κB were detected by HE-staining, gel electrophoretic mobility shift assay （EMSA） and Western-blot methods. The results showed that： （1） The thickening of intima was observed on the 3rd day after balloon-induced injury, and it became more significant on the 7th, 14th and 28th day. The area ratio of intima/media was increased significantly （P〈0.05）; （2） The expression of NF-κB was not detectable in the control group, however, in study group, the expression of NF-κB was detected on the 6th h after balloon-induced injury, reached the peak on the 14th day, and on 28th day, strong expression of NF-κB was observed; （3） The expression of I-κB protein was reduced after balloon-induced injury, and there were significant differences between the study group and the control group （P〈0.05）. It was concluded that the alteration of NF-κB/I-κB system might play an important role in aberrant proliferation within the intima and vascular remodeling following vascular injury. To block NF-κB activation and its role in arterial restenosis initiation may potentially provide a novel therapeutic tool for the treatment and prevention of arterial restenosis.     

Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells and Schwann cells

Background The most important objective of transplant studies in the injured spinal cord has been to provide a favorable environment for axonal growth. Moreover, the continuing discovery of new grafts is providing new potentially interesting transplant candidates. Our purpose was to observe the morphological and functional repair effects of the co-transplantation of neural stem cell （NSC）, Schwann ceils （SCs） and poly lactide-co-glycolide acid （PLGA） on the spinal cord injury of rats.Methods A scaffold of PLGA was fabricated. NSCs and SCs were cultured, with the NSCs labeled with 5-bromodeoxyuridine, and the complex of NSC/PLGA or NSC＋SCs/PLGA were constructed. Thirty-six Wistar rats were randomly divided into three groups： group A （transplantation of PLGA）, group B （transplantation of NSC/PLGA） and group C （transplantation of NSC＋SCs/PLGA）. The 3 mm length of the right hemicord was removed under the microscope in all rats. The PLGA or the complex of PLGA-celIs were implanted into the injury site. Basso-Beattie-Bresnahan （BBB）locomotion scores, motor and somatosensory evoked potential of lower limbs were examined to learn the rehabilitation of sensory and motor function at 4 weeks, 8 weeks, 12 weeks and 24 weeks after injury. All the recovered spinal cord injury （SCI） tissues were observed with HE staining, immunohistochemistry, and transelectronmicroscopy to identify the survival, migration and differentiation of the transplanted cells and the regeneration of neural fibres at 4 weeks, 8 weeks,12 weeks and 24 weeks after injury.Results （1） From 4 weeks to 24 weeks after injury, the BBB locomotion scores of cell-transplanted groups were better than those of the non-cell-transplanted group, especially group C （P 〈0.05）. The amplitudes of the somatosensory evoked potential （SEP） and motor-evoked potential （MEP） were improved after injury in groups B and C, but the amplitude of SEP and MEP at 4 weeks was lower than that at 12 weeks and 24 weeks after injury. Compared with group B, the amplitude of SEP and MEP in group C was improved. The amplitude of SEP and MEP was not improved after injury in group A. （2） HE staining revealed the volume of the scaffold decreased and the number of cells in the scaffold increased. Newly-grown capillaries also could be seen. Immunohistochemistry staining showed the transplanted NSCs could survive and migrate until 24 weeks and they could differentiate into neurons and oligodendrocytes. The regenerated axons were observed in the scaffold-cell complex with transelectronmicroscopy. The above manifestations were more extensive in group C.Conclusions The transplanted NSC can survive and migrate in the spinal cord of rats up to 24 weeks after injury, and they can differentiate into various neural cells. Co-transplantation of cells/PLGA can promote the functional recovery of the injured spinal cord. The effect of co-transplanting NSC＋SCs/PLGA is better than transplanting NSC/PLGA alone.     

Dihydroxyflavonol reduces post-infarction left ventricular remodeling by preventing myocyte apoptosis in the non-infarcted zone in goats

Background Myocyte apoptosis is considered to be the major causative factor of left ventricular （LV） remodeling following myocardial infarction （MI）. We previously reported that 3＇, 4＇-dihydroxyflavonol （DiOHF）, was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study.
Methods Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF （2 mg/kg; i.v., daily） groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays.
Results LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dtrnax. Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle.
Conclusions Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.     

Assessment of culprit lesions by intravascular ultrasound in patients with acute myocardial infarction

Background Intravascular ultrasound has become the standard invasive method for diagnosing coronary artery disease. The aim of the present study was to evaluate the ability of intravascular ultrasound for assessment of culprit lesion morphology during primary percutaneous coronary intervention （PCI） in patients with acute myocardial infarction （AMI）.
Methods We performed 18 intravascular ultrasound assessments preintervention during the primary PCi for AMI. intravascular ultrasound analysis included qualitative and quantitative measurements of reference and lesion external elastic membrane （EEM）, lumen, and plaque plus media （P＆M） area. Positive remodeling was defined as lesion/mean reference EEM 〉1.0. Culprit lesions were identified by a combination of electrocardiogram （ECG） and coronary angiography.
Results There was an average of- 1.44 infarct-related artery （IRA） plaques per patient. The incidences of thrombus and plaque ruptures were 28% （5） and 33% （6）, respectively. Hypoechoic plaque was observed in 72% （13） of AMI patients. Calcified lesions could be found in 33% （6） of culprit lesions. Sixty percent of the culprit lesion sites presented with positive remodeling.
Conclusions Intravascular ultrasound is a safe and feasible imaging modality in patients with AMI and can help identify plaque rupture, intracoronary thrombus or calcification. The culprit lesion site in AMI cases often presents with positive remodeling.     

Inhibitory effects of sunitinib on ovalbumin-induced chronic experimental asthma in mice

Background Tyrosine kinase signaling cascades play a critical role in the pathogenesis of allergic airway inflammation. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, has been reported to exert potent immunoregulatory, anti-inflammatory and anti-fibrosis effects. We investigated whether sunitinib could suppress the progression of airway inflammation, airway hyperresponsiveness （AHR）, and airway remodeling in a murine model of chronic asthma.
Methods Ovalbumin （OVA）-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were intragastrically administered with sunitinib （40 mg/kg） daily during the period of OVA challenge. Twelve hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodeling. The levels of total serum immunoglobulin E （IgE） and Th2 cytokines （interleukin （IL）-4 and IL-13） in bronchoalveolar lavage fluid （BALF） were measured by ELISA. The expression of phosphorylated c-kit protein in the lungs was detected by immunoprecipitation/Western blotting （IP/WB） analysis.
Results Sunitinib significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling in chronic experimental asthma. It reduced levels of total serum IgE and BALF Th2 cytokines and also lowered the expression of phosphorylated c-kit protein in remodelled airways.
Conclusions Sunitinib may inhibit the development of airway inflammation, AHR and airway remodeling. It is potentially beneficial to the prevention or treatment of asthma.     

Effects of granulocyte-macrophage colony stimulating factor on the repair of vessel intima damaged by balloon

Background The dysfunction of vascular endothelial cells plays a key role in starting and facilitating restenosis. The acceleration of intima repair and the recovery of endothelial function would reduce the restenosis rate. This study was undertaken to assess the effect of granulocyte-macrophage colony stimulating factor (GM-CSF) on the repair of damaged iliac arteries.Methods Twenty-four male New Zealand white rabbits undergoing primary iliac artery deendothelialization were randomly divided into two groups (GM-CSF group and control group). The GM-CSF group received a subcutaneous injection of GM-CSF ［10 μg·kg（-1）·d（-1）］, and the control group was given a subcutaneous injection of equivalent saline. The iliac arteries of all animals were damaged by balloon after 7 days. The levels of nitric oxide (NO) were detected before, 1 week, 2 weeks and 4 weeks after angioplasty. The repair and hyperplasia of the intima were observed microscopically and the indices of stenosis were evaluated by computerized planimetry after 4 weeks of angioplasty.Results The NO levels of the GM-CSF group were higher than those of the control group 2 weeks and 4 weeks after angioplasty ［(91.92±11.57) μmol/L vs. (81.67±12.18) μmol/L; (97.67±10.13) μmol/L vs. (83.16±12.64) μmol/L］. Four weeks after balloon damage, histological examination showed that neointima formation, vascular smooth muscle cells and fibrous tissue of the GM-CSF group were less than those of the control group. The endothelium of the GM-CSF group was more integrated, and stenosis of lumen was slighter than that of the control group. Morphometry showed the lumen area of the GM-CSF group was larger than that of the control group ［(1.27±0.31) mm2 vs. (0.92±0.24) mm2］, the neointimal area and percent of intima hyperplasia were significantly smaller than those of the control group ［(0.85±0.34) mm2 vs. (1.18±0.38) mm2; (40±7)% vs. (55±6)%］.Conclusion GM-CSF could facilitate the repair of the intima, reduce neointima formation, better the function of the endothelium, and decrease the rate of restenosis.     

Experimental Study of Adenovirus Vector Mediated-hVEGF165 Gene on Prevention of Restenosis after Angioplasty

This study evaluated the effects of adenovirus vector mediated human vascular endotheli-al growth factor-165 (hVEGF165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenovi-ruses containing hVEGF165 cDNA was directly injected into left side of the injured carotid arteries.On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and im-munohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in ca-rotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer,The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF165 gene transfer the VEGF mRNA and antigen ex-pression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima are-a/media area (I/M), maximal intimal and medial thicknesses (ITmax and MTmax) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of re-combinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit throm-bokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.     

Evidence of apoptotic smooth muscle cells in proliferative intima of injured arteries

Objective To investigate the occurrence and extent of apoptosis in the course of restenosis. Methods The experimental models of vessel narrowness and intima thickness were established in minipigs’ iliac arteries by balloon injury and specimens were retrieved on the 1st, 3rd, 6th,12th and 30th days for dynamic observation. Apoptotic smooth muscle cells (SMCs) were detected by terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling (TUNEL). Results Apoptotic SMCs occurred only in the thickened intima 12 days after injury accompanied with the proliferative SMCs, the percentage of apoptosis was 1. 94%±0. 42% on the 12th day and 1. 36%±0. 31% on the 30th day respectively. The low frequency of apoptosis compared with the proliferative SMCs was a feature in the restenotic pathology. Conclusions Apoptosis participates in the pathogenetic process of intimal thickening and its level was low compared with proliferation. The findings suggest that attempts to modulate apoptosis after vessel injury constitute a theoretical approach to the prevention of restenosis.     

Vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout muce

Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis,postangioplasty restenosis and transplant arteriopathy.Recently,pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis.But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not Vet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene (LDL-/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL-/-mice with the GFP-expressing transgenic mice. LDL-/- mice (22-24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice.Four weeks later,a nonconstrictive cuff was Dlaced around the right femoral artery.After another 2 weeks,both right and left femoral arteries were harvested and subjected to histochemical analysis.Apoptosis was analyzed in situ using TUNEL assay.Resuits Two weeks after cuff placement,atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells, The tissue stained with anti-α smooth muscle actin (SMA) antibody,showed a number of SMA-positive cells in the intimal lesion area.They were also positive for GFP,indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions.Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP.The intima and media showed a larae number of TUNEL-positive signals after 2 weeks cuff injury,indicating the presence of apoptosis in vascular remodelina.Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular inJury under the hypercholesterolemic conditions.Our data also clearly indicate that bone marrow-derived cells differentiated to smooth muscles and endothelial cells in the formation of these lesions in the presence of hypercholesterolemia.     

Increased expression of granulocyte colony-stimulating factor mediates mesenchymal stem cells recruitment after vascular injury

Background  Recent studies indicate that bone marrow-derived cells may significantly contribute to atherosclerosis, post-angioplasty restenosis and transplantation-associated vasculopathy. The responsible bone marrow (BM) cells and mechanisms regulating the mobilization of these cells are currently unclear. The purpose of this study was to investigate the expression of granulocyte colony-stimulating factor (G-CSF) on injured arteries and its effects on mesenchymal stem cells (MSCs) differentiation into vascular smooth muscle cells (VSMCs) in the process of vascular remodeling. 

Methods  Balloon-mediated vascular injury was established in female rats (n=100) which received radioprotective whole female BM cells by tail vein injection and male MSCs through a tibial BM injection after lethal irradiation. The injured and contralateral carotid arteries were harvested at 3, 7, 14 and 28 days after treatment.

Results  Morphometric analysis indicated that intima to media area-ratio (I/M ratio) significantly increased at 28 days, 0.899±0.057 (P <0.01), compared with uninjured arteries. Combining fluorescence in situ hybridization (FISH) and immunohistochemical analysis showed that a significant number of the neointimal cells derived from MSCs, (45.2±8.5)% at 28 days (P=0.01), compared with (23.5±6.3)% at 14 days. G-CSF was induced in carotid arteries subject to balloon angioplasty (fold mRNA change=8.67±0.63 at three days, relative G-CSF protein=0.657±0.011 at three days, P <0.01, respectively, compared with uninjured arteries). G-CSF was chemotactic for MSCs but did not affect the differentiation of MSCs into smooth-muscle-like cells.

Conclusion  Increased expression of G-CSF by injured arteries plays an essential role in contribution to recruitment and homing of MSCs to the site of the arterial lesion.

     

Intervention of Tongxinluo Capsule (通心络胶囊) against Vascular Lesion of Atherosclerosis and Its Effect on Lectin-like Oxidized Low Density Lipoprotein Receptor-1 Expression in Rabbits

Lectin-like oxidized low-density lipoprotein(ox-LDL) receptor-1 (LOX-1) is a newly identifiedreceptor for cytotoxic ox-LDL in endothelial cellsand plays an i mportant role in the occurrence anddevelopment of atherosclerosis ( AS)(1). Clinicalstudies have showed that Tongxinluo capsule (通心络胶囊,TXL) could alleviate the symptoms of angi-na and myocardial ischemia in patients with coro-nary heart disease.But there werefewstudies con-cerning the effect or therapeutic mechanism of itspreve…     

小鼠动脉外膜炎症与内膜细胞因子表达关系的研究

目的 研究近交系野生型小鼠(C57BL／6)股动脉外膜炎症与内膜细胞因子单核细胞趋化蛋白(MCP-1)表达的关系。方法 采用套管法致C57BL／6小鼠股动脉外膜无菌性炎症，行Movat特殊染色辨认动脉管壁的变化；免疫组织化学染色检测动脉内膜MCP-1的表达，确定有无继发的内膜损伤。结果 复制炎症模型2～15天，股动脉外膜炎细胞集聚增加，血管内膜出现MCP-1的表达，而且血管壁渐增厚。结论 C57BL／6小鼠外膜的无茵性炎症能够引起内膜的损伤以及管壁反应性增厚．其可能是粥样硬化性疾病的始动因素之一。     

Intervention of Tongxinluo capsule against vascular lesion of atherosclerosis and its effect on lectin-like oxidized low density lipoprotein receptor-1 expression in rabbits

Objective: To investigate the prevention by Tongxinluo capsule (TXL) of vascular lesions and its effect on the levels of protein and gene expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of vascular wall in rabbits with atherosclerosis (AS), and to explore its possible mechanism against AS.Methods: AS models were established by feeding New Zealand white rabbits with high-cholesterol diet, and 24 immature rabbits were randomly divided into the control group, model group and treated group (treated with TXL capsule). The indexes of total cholesterol (TO and low density lipoprotein (LDL) levels were measured at the 16th week. The intima thickness and the plaque area of abdominal aorta were quantitatively analyzed by pathological morphological analysis, the expression of macrophage and smooth muscle cell (SMC) in intima were detected by immunohistochemical method and histologic segments were stained by Hematoxilin-Eosin (HE) to identify the degree of atherosclerotic lesion in the model group and the prevention by TXL. The LOX-1 gene and protein expression in abdominal aorta was detected by semi-quantitative RT-PCR and immunohistochemistry, respectively.Results: In the model group, the levels of TC and LDL were significantly elevated, aortic intima thickened extensively, the intima area enhanced, and macrophages expression increased; the levels of LOX-1 gene and protein expression was up-regulated in endothelium and neo-intima of the abdominal aorta. The treatment with TXL reduced blood lipids, attenuated arterial intimai proliferation, markedly inhibited the expression of macrophage and excessively expressed the level of LOX-1.Conclusion: TXL has an inhibitory effect on blood lipids, and it can prevent the occurrence of vascular lesion and cure its development, and its protection against AS was possibly associated with a crucial endothelial protective action through lowering the expression of LOX-1 in vascular walls. Supported by the State Natural Science Foundation of China (No. 30371496).     

大鼠血管球囊损伤后血小板活化和血栓形成与再狭窄关系的探讨

目的 :了解大鼠血管球囊损伤后 ,血小板活化和血栓形成对再狭窄的影响。方法 :大鼠 3 5只 ,随机分为①对照组 (C组 ,n =7)仅做左颈总动脉结扎 ;②手术组 (O组 ,n =2 8)做胸主动脉损伤。 2组动物均于术后 6、48h及1、2周采血测GMP 14 0和D dimer含量 ,术后 2周处死动物 ,取出胸主动脉进行病理学观察。结果 :①O组血浆GMP 14 0和D dimer含量显著升高 (P <0 .0 0 1)。②组织学观察 :C组动脉腔内无新生内膜形成 ;O组动脉腔内有明显新生内膜 ,中膜及内膜层有大量的增生细胞 ,内弹力层模糊。结论 :血管内膜损伤可致NO生成减少、血小板活化、血栓形成 ,这是再狭窄的启动因素 ,血管平滑肌细胞增殖 ,内膜增生 ,参与了再狭窄的形成过程。     

葛根素对球囊损伤后再狭窄过程中组织蛋白酶S及胱蛋白C表达的影响

目的研究葛根素对动脉球囊损伤后再狭窄成过程中组织蛋白酶S（cathepsin S，CatS）及其抑制剂胱蛋白C（cystatin C,CysC）表达的影响。方法 建立兔髂－腹主动脉球囊损伤后再狭窄模型，观察应用葛根素治疗前后再狭窄形成的范围、再狭窄局部CatS及其抑制剂CysC的表达变化以及内皮下胶原的变化。结果葛根素组［100mg/(kg·d)］与球囊损伤组比较，再狭窄范围明显减小，差异具有统计学意义（P<0.05）；CatS的表达水平减低，差异具有统计学意义（P<0.05）；CysC表达水平差异无统计学意义（P>0.05）；内皮下胶原含量减少，差异具有统计学意义（P<0.01）。结论葛根素可降低球囊损伤部位再狭窄形成过程中CatS表达、减少斑块内胶原的聚集而发挥一定的抑制再狭窄形成作用，但对CysC调节作用不显著。     

高血胆固醇兔下肢缺血动物模型的建立及形成机制探讨

目的探讨建立高血胆固醇兔下肢缺血模型的方法及其形成机制,观察缺血肢体血运重建情况。方法将34只日本大耳兔随机分成对照组11只,喂以普通饲料;实验组23只,喂以高胆固醇饲料并静脉注射牛血清蛋白;6周后结扎离断股动脉,建立下肢缺血模型,观察血脂水平、颈总动脉斑块形成情况和测定股动脉内膜／中膜厚度比值（I／M）;10周后血管造影观察血管形成情况。结果6周后实验组兔均出现高胆固醇血症,其中12只见颈总动脉粥样硬化斑块（动脉粥样硬化组）,9只未见粥样硬化斑块（高血胆固醇组）,TC、TG、LDL—C、I／M均明显高于对照组（均P〈0.05）;动脉粥样硬化组TC、TG、LDL—C、I／M亦明显高于高血胆固醇组（均P〈O．05）。血管造影示实验组兔新生血管明显少于对照组,镜下可见动脉内皮细胞损害、平滑肌细胞增生。结论高胆固醇饲料喂养结合免疫反应损伤法可成功建立高血胆固醇兔下肢缺血模型,该方法简便易行、可靠,可引起内皮结构和功能损害、内膜增厚,其病理改变与人类动脉粥样硬化的病理过程相似,这为内皮祖细胞移植治疗老年下肢缺血提供了可靠的实验依据。     

小檗碱对兔颈动脉血管成形术后再狭窄的影响

目的:通过观察小檗碱对球囊损伤后兔颈动脉内膜增生与血管重塑的影响,为血管成形术后再狭窄的防治寻找新的治疗策略。方法:日本大耳白兔40只,随机分为假手术组、模型组、小檗碱组和辛伐他汀组,除假手术组外各组均以球囊导管扩张损伤颈动脉内膜,并分别给予生理盐水、小檗碱和辛伐他汀各2.5 mg/(kg.d)腹腔注射,假手术组仅普食喂养。术后15 d取损伤颈动脉段切片,作形态学观察,利用图像分析系统测量血管新生内膜厚度(IT)、管腔面积(LA)、新生内膜面积(IA)、内弹力板围绕面积(IEL)、中膜面积(MA)、外弹力板围绕面积(EEL)。结果:血管球囊损伤后,小檗碱组和辛伐他汀组IT、IA、IA/MA均显著小于模型组(P<0.01)。与模型组相比,小檗碱组和辛伐他汀组LA、IEL、EEL均显著增大(P<0.01),MA则无显著性差异。结论:小檗碱可通过抑制兔颈动脉新生内膜增生与不良的血管重塑,从而为小檗碱防治血管成形术后再狭窄提供了实验基础。