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。     

Biochemical analysis of collagen and elastin synthesis in the balloon injured rat carotid artery.

INTRODUCTION: Balloon catheter denudation of the endothelium in the common carotid artery of the rat is routinely used as a model of neointimal lesion development. The response to endothelial denuding injury involves proliferation and migration of medial smooth muscle cells (SMCs), with the formation of a dramatically thickened neointima. While many studies have focused on the kinetics of the early proliferative and migration responses, much less attention has been paid to the pronounced accumulation of extracellular matrix that occurs as the neointima grows. The purpose of this study was to measure collagen and elastin content, and to assess collagen and elastin synthesis in injured rat carotid arteries. METHODS: Male Sprague-Dawley rats were subject to balloon catheter injury of the left carotid artery using a 2F embolectomy catheter. Rats were sacrificed at different time points after injury, and both carotids left (injured) and right (uninjured and control) were used for measurement of elastin and collagen synthesis (7 days) and content (7, 21 and 60 days). RESULTS: Elastin and collagen syntheses were significantly increased in the injured carotids at 7 days after injury. The increase in elastin synthesis was more dramatic (100% compared to control) than the increase in collagen synthesis (50% compared to control). Both elastin and collagen content were significantly increased by 21 days, and contents were further increased by 60 days in the injured carotid compared to uninjured controls. At 60 days, collagen content of the injured vessels was 2.09+/-0.01 mg/arterial segment compared to 1.32+/-0.08 mg/arterial segment in controls (P=.01). Elastin content of injured vessels was 2.40+/-0.43 mg/arterial segment compared to 1.19+/-0.25 mg/arterial segment in controls (P=.03). CONCLUSIONS: Collagen and elastin contents were significantly increased following injury of the rat carotid. This study provides for the first time a biochemical assessment of collagen and elastin in the balloon-injured rat carotid artery.     

硫化氢在休克肠淋巴液致肝损伤中的作用与机制

 目的： 应用硫化氢（H2S）合成酶胱硫醚γ-裂解酶（CSE）抑制剂DL-炔丙基甘氨酸（PPG）和H2S供体硫氢化钠（NaHS）作用于行肠淋巴液引流的大鼠,探讨H2S在肠淋巴液引流减轻休克大鼠肝损伤中的作用。方法：休克组、休克+引流组、休克+引流+PPG组（45 mg/kg,放血前0.5 h,ip）和休克+引流+NaHS（28 μmol/kg,放血前0.5 h,ip）组大鼠复制失血性休克模型,低血压1 h后行液体复苏,休克+引流组、休克+引流+PPG组和休克+引流+NaHS组在输液结束后,行肠淋巴液引流至液体复苏结束后3 h。观察肝组织形态,检测血浆肝功能生化指标以及肝组织H2S、CSE、Toll样受体4（TLR4）、白细胞介素（IL）-10、IL-12和肿瘤坏死因子α（TNF-α）水平。结果：休克组大鼠血浆天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、总胆汁酸（TBA）以及肝组织H2S、CSE、TLR4、IL-10、IL-12、TNF-α含量均显著高于假手术组;肠淋巴液引流显著降低了休克组大鼠血浆AST、ALT、TBA以及肝组织H2S、CSE、IL-10、IL-12、TNF-α含量;PPG使休克+引流组大鼠血浆AST、ALT、TBA以及肝组织H2S、TLR4、IL-10、IL-12、TNF-α含量进一步降低;NaHS则提高了休克+引流组大鼠血浆AST、ALT与肝组织H2S、TLR4、IL-10、IL-12、TNF-α的含量。组织形态学观察表明,休克组和休克+引流+NaHS组大鼠出现了肝细胞损伤,假手术组、休克+引流组、休克+引流+PPG组大鼠肝细胞形态基本正常。结论：肠淋巴液引流减轻失血性休克大鼠肝损伤的作用机制与抑制H2S生成、减轻H2S介导的炎症反应有关。     

Thrombus organization plays no major role in late neointimal formation after angioplasty in porcine coronary arteries.

Thrombus organization has been suggested to play a major role in late neointimal formation after coronary angioplasty. We sought to describe the time sequence of lesion formation after angioplasty in porcine coronary arteries and to quantify the relation between early thrombosis and late neointimal formation. Deep vessel wall injury was induced by conventional balloon angioplasty in the circumflex (CX) and right coronary (RCA) arteries and by retraction of a chain-encircled balloon in the left anterior descendent artery (LAD). Lesions were assessed by histomorphometry at days 0, 1, 4, 7, 14, 28, and 56 after angioplasty. A response-to-injury index (lesion area/injury length) was determined for each artery. Angioplasty led to rupture/removal of media. Thrombus was present at the exposed adventitia at days 0, 1, and 4. From day 7, neointima was observed on the luminal side of the arterial wall. All thrombus had disappeared at day 28, at which only neointima was observed. Histomorphometry revealed that lesion formation after angioplasty was a gradually increasing process from day 0 to day 28 with no further growth from day 28 to day 56. Maximal thrombus size (day 4, RCA: 0.07+/-0.04 mm, CX: 0.23+/-0.16 mm, LAD: 0.15+/-0.11 mm) was significantly smaller than late neointimal formation (day 28, RCA: 0.68+/-0.18 mm, CX: 0.63+/-0.23 mm, LAD: 0.71+/-0.18 mm) in all three arteries (p < .03). Lesion formation after angioplasty is a gradually increasing process for 4 weeks. Maximal thrombus size is about four times smaller than late neointimal formation. Thus, thrombus organization plays no major role in late neointimal formation.     

硫化氢对高糖诱导的小鼠足突细胞损伤的影响*

 目的： 观察硫化氢对高糖诱导的小鼠足突细胞损伤的影响并探讨其作用机制。方法: 将体外培养的小鼠足突细胞系MPC5分为高糖组、正常糖组、正常糖+DL-炔丙基甘氨酸(PPG)组和高糖+NaHS组。处理后,用Western blotting检测各组细胞胱硫醚γ-裂解酶（CSE)、紧密连接蛋白2（ZO-2）、裂孔蛋白（nephrin）及β-连环蛋白（β-catenin）蛋白水平表达差异。结果: （1）高糖显著降低CSE、nephrin和ZO-2表达（P＜0.05）,而β-catenin的水平明显增高（P＜0.05）,4种蛋白变化均表现出时间依赖性;（2）正常糖培养加不同浓度PPG可显著抑制ZO-2和nephrin的表达（P＜0.05）,显著提高β-catenin的水平（P＜0.05）,3种蛋白变化呈浓度依赖性;（3）高糖诱导的足突细胞加NaHS培养后,ZO-2和nephrin表达可部分恢复（P＜0.01）,β-catenin表达可被部分抑制（P＜0.01）。结论: 本研究结果提示高糖诱导的足突细胞CSE表达降低可能是足突细胞损伤的重要机制之一。而外源性硫化氢对高糖诱导的足突细胞损伤具有一定保护作用,其机制可能与增加ZO-2表达、抑制Wnt/β-catenin通路有关。     

Doxycycline modulates smooth muscle cell growth, migration, and matrix remodeling after arterial injury

The tetracyclines function as antibiotics by inhibiting bacterial protein synthesis, but recent work has shown that they are pluripotent drugs that affect many mammalian cell functions including proliferation, migration, apoptosis, and matrix remodeling. Because all of these processes have been implicated in arterial intimal lesion development, the objective of these studies was to examine the effect of doxycycline treatment using a well-characterized model of neointimal thickening, balloon catheter denudation of the rat carotid artery. Rats were treated with 30-mg/kg/day doxycycline. Doxycycline reduced the activity of matrix metalloproteinase (MMP)-2 and MMP-9 in the arterial wall, and inhibited smooth muscle cell migration from media to intima by 77% at 4 days after balloon injury. Replication of smooth muscle cells in the intima at 7 days was reduced from 28.3 plus minus 2.5% in controls to 17.0 +/- 2.8% in doxycycline-treated rats. The synthesis of elastin and collagen was not affected, but accumulation of elastin was blocked in the doxycycline-treated rats. By contrast, collagen accumulation was not affected, which led to the formation of a more collagen-rich intima. At 28 days after injury, the intimal:medial ratio was significantly reduced from 1.67 +/- 0.09 in control rats to 1.36 +/- 0.06 in the doxycycline-treated rats. This study shows that doxycycline is an effective inhibitor of cell proliferation, migration, and MMP activity in vivo. Further study in more complicated models of atherosclerosis and restenosis is warranted.     

动脉粥样硬化大鼠血管损伤后局部组织学结构的变化

目的建立大鼠颈总动脉球囊损伤模型，了解血管成形术后再狭窄的发生规律及病理机制。方法在大鼠动脉粥样硬化病变的基础上，使用2F球囊导管损伤大鼠左侧颈总动脉，观察术后不同时期内膜、中膜增生的动态改变；对血管壁增殖的细胞进行鉴定；观察血管壁平滑肌细胞表型标志物SMα—actin表达的变化。结果损伤后7天薪生内膜开始形成，至3月时内膜增厚达最大，管腔明显狭窄，损伤动脉壁可见细胞大量增殖，大部分为平滑肌细胞。损伤早期血管壁表达SMα—actin减少，至损伤后期逐渐恢复至原有水平。结论应用球囊导管可以成功建立大鼠血管损伤动物模型，损伤后新生内膜增生导致管腔狭窄，平滑肌细胞的表型改变、迁移及增殖是内膜过度增生的病理基础。     

The degree of neointimal formation after stent placement in atherosclerotic rabbit iliac arteries is dependent on the underlying plaque.

The purpose of this study was to determine the effects of stent placement on the underlying arterial morphology and the relations of stent-vessel wall interactions with subsequent neointimal formation in an atherosclerotic artery. Seven New Zealand White rabbits with experimentally induced atherosclerosis underwent balloon angioplasty (n = 7) and stent placement after balloon angioplasty (n = 7) in the iliac arteries. Histologic analysis of the treated arteries was performed at 28 days to assess device interactions with the artery and the pattern of the neointimal response. The area within the external elastic lamina of the stented vessels was 66% greater than the arteries with balloon angioplasty alone (p = 0.001) which contributed to a significantly greater late lumen area (3.33 +/- 0.51 mm2 versus 1.33 +/- 0.20 mm2, p = 0.0028). Neointimal thickness was measured at 220 stent wire sites from 21 sections of stented arteries of which 139 (63%) had underlying plaque and 81 (37%) were adjacent to normal media. Rupture of the internal elastic lamina (IEL) occurred at only 9 (11%) of the 81 stent wire sites over normal media. The mean neointimal thickness was 0.16 +/- 0.01 mm lor all stent wire sites. The neointimal thickness was greater at the stent wire sites with underlying plaque (0.23 +/- 0.01 min) than at the stent wire sites adjacent to normal media (0.08 +/- 0.01 mm) or at sites with rupture of the internal elastic lamina (0.16 +/- 0.02 mm, p = 0.0001). The degree of neointimal formation within the stents strongly correlated with the area of the underlying atherosclerotic plaque (r = 0.76, p = 0.0007) and the extent of plaque or medial compression by the struts (r = 0.90, p = 0.006). The present study characterizes stent interactions in a model commonly employed to evaluate novel therapies for the prevention of restenosis. The neointimal response was influenced by the local arterial morphology and correlated with the extent of plaque or medial compression by the stent. These data may be useful for future studies in this model and understanding the mechanism of in-stent restenosis.     

强力霉素影响基质金属蛋白酶活性和血管重构的实验研究

目的：观察强力霉素对损伤动脉组织中基质金属蛋白酶（MMP）活性的抑制作用，并探讨强力霉素对血管平滑肌细胞增殖、动脉内膜增生、管腔重构的影响。方法:球囊导管扩张动脉的方法建立大鼠颈总动脉损伤模型。治疗组用强力霉素30 mg·kg^-1·d^-1干预。明胶酶谱法测定损伤动脉组织中MMPs的活性。用HE染色、VVG染色、免疫组化标记α-actin和增殖细胞核抗原的方法观察损伤动脉内膜厚度、管腔重构及平滑肌细胞增殖的情况。结果:①强力霉素治疗组MMP-9活性在术后24 h、3 d分别比对照组低26.3％、34.5％（P<0.01）；MMP-2活性在术后7 d比对照组低40.0％（P<0.01）。②强力霉素治疗使术后7 d内膜平滑肌细胞增殖率（43.23％±1.06％）显著低于对照组（62.76％±1.02％）（P<0.01）；使术后14 d、28 d新生内膜厚度比对照组分别少32.0％、38.8％（P<0.01），而管腔面积比对照组多58.0％、90.4％（P<0.01） 。结论：强力霉素可以显著降低血管损伤后MMPs活性，抑制内膜平滑肌细胞的增殖、新生内膜增生以及管腔重构，提示它可能具有防治PTCA术后再狭窄的作用。     

Total sleep deprivation augments balloon angioplasty-induced neointimal hyperplasia in rats

Sleep deprivation has been shown to be associated with an increase in inflammation that is also involved in the development of neointimal hyperplasia (or restenosis). The purpose of this study was to investigate whether total sleep deprivation (TSD) would worsen neointimal formation by balloon injury. Sixteen rats were randomly allocated into the following four groups: group 1, balloon angioplasty alone; group 2, TSD prior to angioplasty; group 3, angioplasty before TSD; and group 4, TSD before and after angioplasty. Total sleep deprivation was induced by the disc-over-water method, and balloon angioplasty was performed in the carotid artery. Histopathological analysis and assay of cytokines were applied to evaluate the effects of TSD in this study. Total sleep deprivation significantly increased the ratio of postinjury neointima-to-media area in groups 2, 3 and 4 (all P < 0.01) compared with group 1. Additionally, in all groups with TSD administration the serum level of interleukin 10 was also markedly decreased on day 3 after angioplasty injury (P < 0.05 or P < 0.01). Our findings suggest that perioperative TSD can significantly augment neointimal hyperplasia of the carotid artery in rats, which may be partly caused by a TSD-induced effect in suppressing the serum level of the anti-inflammatory cytokine, interleukin 10.     

罗格列酮抑制大鼠颈动脉球囊损伤后新生内膜增生和基质金属蛋白酶-2的表达

目的探讨PPARγ配体罗格列酮对大鼠颈动脉球囊损伤后新生内膜增生及MMP-2和TIMP-2表达的影响。方法实验分为给药组(罗格列酮3 mg/kg.d)和对照组(0.9%氯化钠注射液),每组n=5。用球囊血管内膜剥脱法建立大鼠颈动脉再狭窄模型。HE染色检测血管内膜与中膜的厚度比和面积比。RT-PCR和Western blot法检测血管组织中MMP-2和TIMP-2的mRNA和蛋白质的表达。结果罗格列酮明显抑制球囊损伤后血管新生内膜增生,与对照组相比,术后所有时间点上内膜与中膜的厚度比及面积比均显著减少(P<0.001)。罗格列酮组与对照组比较显著抑制球囊损伤后各时间点血管中基质金属蛋白酶-2(MMP-2)的mRNA和蛋白的表达,术后1、7、14、28 d蛋白表达由对照组的0.605±0.007、1.000±0.002、0.890±0.014和0.290±0.028降至0.310±0.014、0.525±0.021、0.405±0.007和0.081±0.004(P<0.001)。但罗格列酮对MMP-2抑制剂TIMP-2的mRNA和蛋白表达无影响。结论罗格列酮抑制大鼠颈动脉球囊损伤后新生内膜增生,其机制可能与MMP-2的表达下调及MMP-2/TIMP-2表达失衡有关。     

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。     

Inhibition of neointimal proliferation of rat carotid artery by sulodexide.

Sulodexide, a glycosaminoglycan-containing compound, is known to have an antiproliferative effect on vascular smooth-muscle cells, in vitro, as well as antithrombotic and fibrinolytic effects. But there are few reports about the effect of neointimal proliferation in vivo. In this study, we examined whether Sulodexide was effective in the inhibition of neointimal proliferation after vascular injury. Ten-week-old Sprague-Dawley rats were subjected to vascular injury by endothelial denudation of the common carotid artery by using a balloon catheter. They were then allocated randomly into a control group (saline 2 ml for 3 days, and then 1 ml for 18 days, IM) and a treated group (Sulodexide 10 mg/kg/day for 3 days, and then 4 mg/kg/day for 18 days, IM). Three weeks after vascular injury, we analyzed the neointimal proliferation using morphometry. The neointimal proliferation was significantly reduced in the treated group compared to the control group (Ratio of neointimal area to medial area; 118.39 +/- 6.80% in the treated group, 177.25 +/- 17.25% in the control group). This result showed that Sulodexide might be effective in reducing the rate of restenosis after balloon angioplasty.     

硫化氢对大鼠离体灌流心脏心功能的影响

目的：观察H2S对大鼠离体心脏心功能的影响，以探讨内源性H2S对心肌活动的调节意义。方法： 检测大鼠心肌组织中H2S的含量及生成率，并采用RT-PCR方法检测心肌组织CSE(内源性硫化氢合成的关键酶)mRNA的表达；应用Langendorff灌流大鼠离体心脏，用不同浓度NaHS(10-6-10-3mmol/L)灌流心脏，及用生理浓度NaHS(4×10-4mol/L)持续灌流20 min，测量心率(HR)、左室内压差(△LVP＝左室收缩压-左室舒张压)、左室内压变化速率(±dp/dtmax)、冠脉灌流量(CPF)等指标；应用KATP通道阻断剂格列苯脲预灌流，后给予生理剂量NaHS灌流，观察其是否可以阻断NaHS的效应。结果： NaHS可以呈浓度依赖性抑制左心室±dp/dtmax及△LVP(P＜0.05)，但对HR、CPF没有影响，生理剂量NaHS持续灌流20 min内，可以持续抑制±dp/dtmax及△LVP(P＜0.05)，而对HR、CPF几乎没有影响。KATP通道阻断剂格列苯脲可以大部分(85.7%)阻断生理剂量NaHS对心功能的抑制效应。结论： 内源性H2S可能通过开放心肌KATP通道，抑制大鼠离体心脏左心室的收缩功能。     

alpha5beta1 integrin expression and luminal edge fibronectin matrix assembly by smooth muscle cells after arterial injury

Fibronectin is secreted from the cell as a soluble protein that must then polymerize to regulate cell function. To elucidate the process of fibronectin matrix assembly in vascular disease, we immunostained sections of balloon-injured rat carotid artery for the fibronectin-binding alpha5beta1 integrin. Whereas alpha5beta1 integrin was not evident in the normal carotid artery, its expression was induced after a vascular injury. By 14 days, the alpha5beta1 integrin was localized exclusively to the less differentiated smooth muscle cells (SMCs) at the luminal surface of the neointima. Platelet-derived growth factor-BB, dominant in neointimal formation, selectively increased the expression of the alpha5beta1 integrin by human SMCs in culture. To track the assembly of fibronectin fibers, fluorescence-labeled soluble fibronectin protomers were added to cultured SMCs and to fresh segments of normal and balloon-injured rat carotid arteries. Fibronectin fiber formation in cultured SMCs could be detected within 10 minutes, and was blocked by an RGD peptide, an anti-beta1 integrin antibody, and an anti-alpha5beta1 integrin antibody, but not by an anti-beta3 integrin antibody. En face confocal microscopy of arterial segments revealed that soluble fibronectin had polymerized on the alpha5beta1 integrin-expressing SMCs of the luminal surface of the injured arterial neointima, but not on the alpha5beta1 integrin-negative neointimal SMCs below this or on the endothelial cells of uninjured arteries. Furthermore, in situ fibronectin assembly by the neointimal SMCs was inhibited by an RGD peptide and by an anti-beta1 integrin antibody. These studies indicate that a subpopulation of SMCs in the repairing artery wall orchestrates integrin-mediated fibronectin assembly.     

Potential role of CYLD (Cylindromatosis) as a deubiquitinating enzyme in vascular cells

Data from several studies suggest that the ubiquitin-proteasome system may play a role in the progression of atherosclerosis. Here, we examined the potential role of the deubiquitinating enzyme CYLD (cylindromatosis), mutation of which has been reported to cause familial cylindromatosis. Northern blot analysis revealed expression of CYLD mRNA in the aorta, as well as in cultured human aortic endothelial cells (ECs) and vascular smooth muscle cells. Treatment with recombinant tumor necrosis factor (TNF)-alpha significantly increased CYLD expression in ECs and vascular smooth muscle cells. Immunostaining showed CYLD expression in atherosclerotic lesions from human carotid arteries and up-regulation of CYLD expression in the neointima of rat carotid arteries after balloon injury. Overexpression of CYLD in ECs resulted in inhibition of TNF-alpha-induced nuclear factor-kappaB activity through deubiquitination of TNFR-associated factor 2 (TRAF2), whereas overexpression of catalytically inactive CYLD had no effect. CYLD overexpression also inhibited expression of cyclin D1 and activation of the E2F pathway through deubiquitination of the upstream molecule Bcl-3 and inhibition of its translocation into the nucleus. Overexpressed CYLD also significantly inhibited cell viability. Furthermore, overexpression of CYLD in rat balloon-injured carotid artery attenuated neointimal formation through inactivation of nuclear factor-kappaB and E2F. In conclusion, these data demonstrate that the deubiquitinating enzyme CYLD may inhibit inflammation and proliferation in vascular cells and may represent a novel target for the treatment or prevention of atherosclerosis.     

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。     

内源性H2S对LPS所致大鼠急性肺损伤时肺动脉高压的影响及其与一氧化氮的相互作用

目的： 探讨硫化氢（H2S）对脂多糖（LPS）所致急性肺损伤时肺动脉高压（PAH）的影响及H2S/胱硫醚-γ-裂解酶（CSE）体系和一氧化氮（NO）/一氧化氮合酶（NOS）体系在其发生机制中的相互作用。 方法： 将72只大鼠随机分为生理盐水（NS）对照组、LPS组、LPS+L-NAME组、LPS+PPG组，检测给药后2、4、6、8 h的平均肺动脉压（mPAP），以及4、8 h血浆H2S、NO含量和iNOS、cNOS活性、肺组织NO含量和iNOS、cNOS、CSE活性，免疫组化法测定肺组织iNOS蛋白表达，并结合肺光镜形态等指标综合评价肺损伤程度。 结果： LPS组各时点的mPAP显著高于对照组，给药后4、8 h，NO含量、iNOS活性和蛋白表达升高，cNOS活性及H2S含量、CSE活性降低，肺组织损伤较重。预先给予L-NAME可减轻LPS所致上述指标的改变。而预先给予PPG可加重LPS所致肺损伤，但对cNOS活性无明显影响。 结论： LPS使内源性H2S减少导致mPAP升高； H2S/CSE体系与NO/NOS体系共同参与LPS所致急性肺损伤时PAH形成的调控机制，在其中呈相互的负性调节作用。