Increased inflammatory cell infiltration and matrix metalloproteinase-1 expression in atherosclerotic plaque of diabetic rabbits

Objective The aim of the present study was to examine levels of inflammatory cell infiltration and matrix metalloproteinase (MMP)-1 expression in atherosclerotic plaques of diabetic rabbits. Methods Diabetes was induced in rabbits by alloxan injection, and atherosclerotic plaque formation was stimulated both in diabetic and non-diabetic (sham-injected) rabbits by balloon injury of the abdominal aorta together with high lipid feeding. The morphology of atherosclerosis thus generated was studied by angiography and intravascular ultrasound (IVUS). Transverse sections of diseased aorta were examined by immunohistochemistry to analyze numbers of macrophages and smooth muscle cells as well as expression of MMP-1.     

Retinoschisis and intravitreal ranibizumab treatment for myopic choroidal neovascularization

Background Intravitreal ranibizumab injection is effecitve on treating myopic CNVs,but it could be a risk factor for developing more severe retinoschisis in eyes with preexisted retinoschisis and epiretinal membrane.This study aimed to explore the incidence and features of retinoschisis after intravitreal ranibizumab injection for myopic choroidal neovascularization.Methods Eighty-three eyes of 81 patients with choroidal neovascularization secondary to pathologic myopia were treated with intravitreal ranibizumab injection.The best corrected visual acuity and optical coherence tomography （OCT） images were recorded at baseline and every month thereafter.Central retina thickness and maximal retina thickness were measured.The subjects were divided into three groups.Eleven eyes that had retinoschisis and epiretinal membrane were in group 1,six eyes that had simple epiretinal membrane were in group 2,and 66 eyes that had neither retinoschisis nor epiretinal membrane were in group 3.Six contralateral eyes in group 1 which had retinoschisis and epiretinal membrane but were not treated with intravitreal ranibizumab injection were set as the control group.Results Seven of the 11 eyes in group 1 developed more severe retinoschisis,the mean maximal retinal thickness increased from （380.28±90.13） to （467.00±70.20） μm （P 〈0.05）.The retinoschisis of all 6 eyes of the control group did not aggravate.Compared with the control group,the aggravation ratio of retinoschisis increased significantly （P 〈0.05）.No new onset of retinoschisis took place in group 2 and group 3.Conclusion Intravitreal ranibizumab injection may be a risk factor for aggravation of retinoschisis in eyes with preexisted retinoschisis and epiretinal membrane.     

Ultrasound-mediated microbubble delivery of pigment epithelium-derived factor gene into retina inhibits choroidal neovascularization

Background Many studies have suggested that the imbalance of angiogenic factor and anti-angiogenic factor expression contributes significantly to the development of choroidal neovascularization （CNV）, and ultrasound microbubble combination system can increase the gene transfection efficiency successfully. This study was designed to investigate whether ultrasound-mediated microbubble destruction could effectively deliver therapeutic plasmid into the retina of rat, and whether gene transfer of pigment epithelium-derived factor （PEDF） could inhibit CNV.
Methods Human retinal pigment epithelial cells were isolated and treated either with ultrasound or plasmid alone, or with a combination of plasmid, ultrasound and microbubbles to approach feasibility of microbubble-enhanced ultrasound enhance PEDFgene expression; For in vivo animal studies, CNV was induced by argon lasgon laser in rats. These rats were randomly assigned to five groups and were treated by infusing microbubbles attached with the naked plasmid DNA of PEDF into the vitreous of rats followed by immediate ultrasound exposure （intravitreal injection）; infusing liposomes with the naked plasmid DNA of PEDF into the vitreous （lipofectamine ＋ PEDF）; infusing microbubbles attached with PEDF into the orbit of rats with ultrasound irradiation immediately （retrobular injection）; infusing microbubbles attached with PEDF into the femoral vein of rats with exposed to ultrasound immediately （vein injection）. The CNV rats without any treatment served as control. Rats were sacrificed and eyes were enucleated at 7, 14, and 28 days after treatment. Gene and protein expression of PEDF was detected by quantitative real-time RT-PCR, Western blotting and immunofluorescence staining, respectively. The effect of PEDF gene transfer on CNV was examined by fluorescein fundus angiography.
Results In vitro cell experiments showed that microbubbles with ultrasound irradiation could significantly enhance PEDF delivery as compared with microbubbles or ultrasound alone. In the rat CNV model, transfection efficiency mediated by ultrasound/microbubbles was significantly higher than that by lipofectamine-mediated gene transfer at 28 days after treatment. The study also showed that with the administration of ultrasound-mediated microbubbles destruction, the CNV of rats was inhibited effectively.
Conclusions Ultrasound-microbubble technique could increase PEDF gene transfer into rats＇ retina and chorioid, in association with a significant inhibition of the development of CNV, suggesting that this noninvasive gene transfer method may provide a useful tool for clinical gene therapy.     

A new rat model of glaucoma induced by intracameral injection of silicone oil and electrocoagulation of limbal vessels

Background  A satisfied glaucoma model is absent now. The aim of this study was to evaluate the effect of a combination of intracameral injection of silicone oil and electrocoagulation of corneal limbal vessels and episcleral veins in the rats to establish glaucoma model.

Methods  Operation was performed in each of the left eyes of 90 adult male rats. Right eyes were used as controls. Measurement of intraocular pressure (IOP) was performed with an applanation tonometer (Tono-Pen). Retinal ganglion cells (RGCs) were retrogradely labeled by applying FluoroGold onto the bilateral superior colliculus.

Results  During the follow-up (24 weeks), the IOP of the study eyes was significantly higher (P <0.05) than the control eyes (at final examination, IOP of control eyes was (13.4±1.0) mmHg and IOP of study eyes was (16.1±1.8) mmHg). Correspondingly, at 24 weeks after operation, the RGCs density of the study eyes (2286.11±290.45/mm²) was significantly lower than the control eyes (2626.46±164.85/mm², P <0.01). In the operated eyes, histological examination showed excavation of optic disc and increased neuroglial cells in the optic nerve, reduced thickness of retina and diminution of retinal ganglion cells, and atrophy of ciliary body and iris. Notably, the anterior chamber angle of the operated eye remained open.

Conclusions  A combination of intracameral injection of silicone oil and electrocoagulation of corneal limbal vessels and episcleral veins may establish a reliable glaucoma model for further research.

     

EFFECT OF FUNDUS PIGMENT ON RESPONSE OF RABBIT RETINA TO TRANSPUPILLARY THERMOTHERAPY

Objective To study the effect of fundus pigment on the response of the retina to transpupillary thermotherapy （TTT）. Methods The retina were irradiated with 810 nm diode laser in 16 eyes of 8 pigmented rabbits and 12 eyes of 6 albino rabbits. The spot size was 1.2 mm; the duration was 60 s; and powers were 50, 80, 150 and 300 mW for pigmented rabbits and 800, 1 200 and 1 500mW for albino rabbits. All of the eyes were followed up with ophthalmolscope. The fundus was photographed and examined histologically with optic microscope immediately and 1 month after TTT respectively. Results The changes of the fundus and the histological examination were not significant immediately and 1 month after TTT in 50 mW group of pigmented rabbit and 800 mW of albino rabbit. Grey spot on the retina was observed on the fundus in 80 mW group of pigmented rabbit and 1 200 mW of albino rabbit immediately after TTT. The structure of the retina remained intact and subretinal fluid was observed histologically. Grey spot was still visible on the fundus, though the fluid was absorbed after 1 month. As the power of diode laser was increased to 150 mW for pigmented rabbits and 1500 mW for albino rabbit, fundus white spots were observed and the outer retina was destroyed while photoreceptors existed immediately after TTT. Pigmentation was found in white lesions and the fibrous proliferation was found in choroid 1 month after TTT. Prominent white spot was seen on the fundus immediately after laser irradiation of 300 mW in pigmented rabbits and the structure of the retina was obscured. One month after TTT, dense pigmentation appeared at laser lesions. The retina was thinner. There was prominent fibrous proliferation in the choroid. Conclusion The fundus pigment seems to play an important role in the response of the retina to TTT. The reaction of the retina is in proportion to the intensity of laser.     

增生性糖尿病视网膜病变眼内组织型纤溶酶原激活物及其抑制物的表达与血管内皮生长因子表达的相关性

目的 探讨增生性糖尿病视网膜病变(PDR)中组织型纤溶酶原激活物(t-PA)及纤溶酶原激活物抑制剂(PAI)的表达及其与血管内皮生长因子(VEGF)表达的相关性.方法 在玻璃体手术中采集PDR 35眼玻璃体,同时采集因黄斑裂孔行玻璃体手术20眼玻璃体作为对照组,采用酶联免疫吸附法检测t-PA和PAI的表达浓度,并与VEGF的表达进行相关性分析.结果 PDR眼玻璃体中VEGF、t-PA及PAI的表达浓度与对照眼玻璃体中的表达浓度比较差异有统计学意义(P＜0.01).t-PA及PAI的表达与VEGF的表达经统计学分析,差异有统计学意义(P＜0.01).结论 在PDR眼内视网膜新生血管的发生过程中不但有VEGF,还可能同时有多种生物活性物质的参与. Abstract： Objective To evaluate the correlation between the expression of tissue plasminogen activator(t -PA)and plasminogen activator inhibitor(PAI)with vascular endothelial growth factor (VEGF)expression in proliferative diabetic retinopathy(PDR).Methods Vitreous samples were taken from 35 eyes with PDR and analyzed with enzyme linked immunosorbent assay(ELISA)for the expression of VEGF, t - PA and PAI.Control samples were from 20 eyes with idiopathic macular hole and analyzed in the same way.The correlation between VEGF expression and the expression of t - PA and PAI in proliferative diabetic retinopathy were studied.Results VEGF, t - PA and PAI were significantly expressed as compared with those in control subjects(P ＜0.01).The expression of t- PA and PAI were highly correlated with that of VEGF in proliferative diabetic retinopathy(P ＜ 0.01).Conclusions It is suggest that a number of bioactive substances may be involved in the pathogenesis of angiogenesis in PDR.The expression of t - PA may beupregulated by the activation of VEGF, which may further facilitate the process of angiogenesis in PDR.Meanwhile, the correlated expression of PAI may suggest the presence of an endogenous angiogenesis mechanism accompanying the activities of VEGF.     

Therapeutic effect of bFGF on retina ischemia-reperfusion injury

Background Basic fibroblast growth factor (bFGF) plays important roles in retina degeneration, light injury, mechanical injury, especially in retina ischemia-reperfusion injury (RIRI). This study was to investigate the therapeutical effect of bFGF on RIRI and its mechanisms.Methods Experimental RIRI was induced by increasing intraocular pressure (IOP) in the eyes of 48 rats. These rats were divided into normal control, ischemia-reperfusion and bFGF-treated groups.Histological and ultrastructural changes of in the retina of different groups were observed, and the number of retinal ganglion cells (RGCs) was quantitatively analyzed under microscopy. Apoptotic cells were detected using the TdT-dUTP terminal nick-end labeling (TUNEL) method. The expression of caspase-3 was determined by streptavidin peroxidase (SP) immunohistochemistry. Atomic absorption spectrum method was used to evaluate the intracellular calcium changes.Results At the early stage of retinal ischemia-reperfusion injury, retina edema in the treated group was significantly eliminated compared with the untreated ischemic animals. RGCs in the bFGF-treated group was more than those in the untreated ischemic group during the post-reperfusion stages. In ischemic group, apoptotic cells could be found at 6th hours after reperfusion and reached the peak at 24th hours. At 72th hours no apoptotic cells could be found. The changes in caspase-3 expression had a similar manner. The intracellular calcium of rat retina began to increase at lth hour, reached the peak at 24 hours, and began to decease at 72th hours. The change of the three markers in the treatment group showed a similar pattern, but they were all relatively less obvious.Conclusion Apoptosis may play a vital role in RIRI. bFGF may has therapeutical effects on RIRI by inhibiting the increase of intracellular calciums and caspase-3 expression.     

EFFECT OF RADIX SALVIAE MILTIORRHIZAE ON THE GENE EXPRESSION OF NITRIC OXIDE SYNTHASE IN ISCHEMIC RAT BRAINS

The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains daring ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. It was found that NOS gene expression of cerebral cortex and caudate-putamen was markedly increased in 24 hours in ischemia group (P< 0.01). In RSM-treated rats, although the NOS gene expression of ischemic side was also increased as compared with contralateral cortex and caudate-putamen, it was significantly lower in RSM-treated rats than those of the controls (P< 0.05, P< 0.01). The present study indicates that RSM can partly inhibit NOS gene ex pression of cerebral cortex and caudate-putamen during ischemia. This may be one of the protective mechanisms of RSM on cerebral ischemia.     

ET-1 GENE EXPRESSION OF RAT BRAIN DURING ISCHEMIA AND REPERFUSION AND THE PROTECTIVE EFFECT OF RADIX SALVIAE MILTIORRHIZAE

Endothelin-1 (ET-1) gene expression of rat brain during ischemia and reperfusion as well as the effect of Radix Salviae Miltiorrhizae (RSM) were studied with in situ hybridization. It was found that ET-1 gene expression of cerebral cortex and caudate-putamen was markedly increased both in 24 hours of ischemia and 24 hours of reperfusion groups (P< 0.01, P< 0.05). In RSM-treated rats, although the ET-1 gene expressions of ischemia and reperfusion sides were also increased as compared with contralateral cortex and caudate-putamen, they were significantly lower in RSM-treated rats than those of controls (P< 0.05, P< 0.01 respectively). The present study indicated that RSM can partly inhibit ET-1 gene expression of cerebral cortex and caudate-putamen during ischemia and reperfusion. This may be one of the protective mechanisms of RSM on cerebral ischemia and reperfusion.     

Protection of retina from lipid peroxidation with super''''oxide dismutase

Our previous experiments demonstrated the occurrence of retinal lipidperioxidation following vitreous hemorrhage.In the present study,0.2ml ofautologous whole blood was injected into the vitreous of both eyes in rabbits.One eye of each rabbit received an additional injection of 0.2ml of superoxidedismutase (SOD,794 U);the other eye served as a control.The malondialdehyde(MDA) in the retina was assayed with fluorescence spectrophotometry.The resultsshowed that the MDA was significantly lower in eyes injected with SOD (0.047±0.010 nmol/mg) than in control eyes (0.096±0.011 nmol/mg,P<0.05) 10d afterinjection.Ultrastructural examination revealed that the photoreceptor cells of theeyes with SOD injection were relatively normal.It is suggested that SOD can pro-tect the retina from lipid peroxidation.     

电压门控性氯通道3在高眼压模型大鼠小梁网中的表达

目的: 检测电压门控性氯离子通道3(ClC-3)在大鼠小梁网中的表达情况,探讨其在青光眼发病机制中的可能作用。方法: 30只健康雄性大鼠。左眼作为正常对照,右眼前房内注射玻璃酸钠,每周1次,连续10周,制备高眼压模型,每次全麻后玻璃酸钠注射前采用Tono-Pen XL眼压计测量双眼眼压并记录。实验分为正常对照组、玻璃酸钠注射3周组和10周组。分别取3组大鼠的小梁网组织,采用RT-PCR法检测ClC-3mRNA表达水平,免疫组织化学法检测ClC-3蛋白的表达。结果: 玻璃酸钠注射后1、3和10周,大鼠右眼眼压均较注射前增高(P<0.01),注射后1周眼压值较注射前轻微增高,注射后3周眼压较注射前明显增高,但眼压值未达到高眼压成模标准,注射后10周眼压值较注射前明显增高,达到高眼压成模标准。RT-PCR法检测,与正常对照组比较,玻璃酸钠注射3周组大鼠小梁网组织中ClC-3 mRNA表达水平明显增高(t=7.88,P<0.05);玻璃酸钠注射10周组大鼠小梁网组织中ClC-3 mRNA表达水平明显降低(t=15.93,P<0.05)。免疫组织化学检测,3组大鼠小梁网组织中ClC-3蛋白表达均为阳性,玻璃酸钠注射3周组大鼠小梁网组织中ClC-3蛋白表达强度较正常对照组大鼠增强,玻璃酸钠注射10周组大鼠小梁网组织中ClC-3蛋白表达强度较正常对照组大鼠减弱。结论: 大鼠小梁组织中存在ClC-3的表达,ClC-3可能与小梁网的病理调节有关联,进而参与青光眼的发病。     

腺病毒介导脑源性神经营养因子基因转染在大鼠视网膜中的表达

目的 :研究腺病毒介导脑源性神经营养因子 (brain derivedneurotrophicfactor,BDNF)基因转染在活体大鼠视网膜的表达 .方法 :将BDNF腺病毒注入大鼠玻璃体内 ,于不同时间点免疫荧光染色检测表达 ;酶联免疫吸附实验 (enzymelinkedimmunosorbentassay ,ELISA)检测转染因素、损伤因素对视网膜表达BDNF的影响 .结果 :免疫荧光染色显示 3d节细胞即出现绿色荧光 ,可持续 4wk ,对照组荧光着色细胞数、荧光强度均低于各时间点转染组 ;ELISA显示经BDNF转染各组在各时间点表达均显著高于非转染组 (P <0 .0 1 ) ,损伤非转染组在 3d和 1wk时高于正常组 (P <0 .0 1 ) .结论 :腺病毒介导BDNF基因转染可在大鼠视网膜有效表达 ,损伤可以导致早期的BDNF表达升高     

玻璃体内注射曲安奈德对兔眼的毒性作用

目的观察玻璃体内注射曲安奈德对兔角膜、晶状体、睫状体和视网膜的毒性作用。方法32只灰兔分为四组(n=8),玻璃体内分别注射乳酸林格氏缓冲液(对照组)、4 mg曲安奈德(B组)、1.3 mg曲安奈德(C组)和载体(D组)。于注射前和注射后不同时间点分别进行眼压及明、暗适应视网膜电图检查;于术后1周、1月和3月,每组分别取2眼观察组织学和超微结构的改变。结果与其他各组比较,B组注射后1 d和1、2周的眼压显著上升(P<0.05)。术后1周和1月,B组和D组视网膜电图各峰值较对照组和C组明显下降(P<0.05)。光镜下B组视网膜组织受损;电镜下B组和D组的睫状体、晶状体和视网膜组织均不同程度受损。结论玻璃体内注射曲安奈德和载体后,对兔晶状体、睫状体和视网膜组织可能有一定的毒性作用。     

重组人促红细胞生成素对急性高眼压兔视网膜bcl-2蛋白表达的影响

目的探讨全身应用重组人促红细胞生成素(rhEPO)对急性高眼压兔眼视网膜bcl-2蛋白表达的影响及意义。方法在设立正常对照、急性高眼压模型对照的情况下,日本大耳白兔皮下注射rhEPO,分别于造模后第1、3、7、14天免疫组化法观察视网膜bcl-2蛋白表达。结果正常视网膜组织可见bcl-2蛋白表达,染色阳性细胞数为每高倍视野(10.5±1.2)个。模型组和EPO组兔眼视网膜bcl-2蛋白表达阳性细胞数均较正常对照组减少(P<0.05,P<0.01)。EPO组第7天、14天视网膜bcl-2蛋白表达阳性细胞数较模型组增加(P<0.05,P<0.01)。结论rhEPO可以上调视网膜bcl-2蛋白表达,这可能是rhEPO保护急性高眼压引起的兔眼视网膜神经功能损害的机制之一。     

Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina

Background Neural stem cells （NSCs） transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentJatJon of brain-derived neurotrophic factor （BDNF） gene transgenic NSCs transplanted into the normal rat retinas. Methods NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs （BDNF-NSCs） and control cells （p-NSCs）. The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction （FQ-PCR） and enzyme-linked Jmmunosorbent assay （ELISA）. BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein （AAV-EGFP） to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution （PBS） served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph （HRA） and immunohistochemistry, respectively. Results NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR （P 〈0.05） and at protein level measured by ELISA （P 〈0.05）, which showed that BDNF was overexpressed in BDNF-NSCs. The results of HRA demonstrated that graft cells could survive well and migrate into the host retinas, while the immunohistochemical analysis revealed that transplanted BDNF-NSCs differentiated into neuron more efficiently compared with the control NSCs 2 months after transplantation. Conclusions The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in the normal host retinas.     

色素上皮源性因子基因转染对巨噬细胞诱导大鼠增生性玻璃体视网膜病变的抑制作用及其机制

目的：探讨玻璃体腔注射色素上皮源性因子(PEDF)基因真核表达载体在增生性玻璃体视网膜病变(PVR)模型眼内的表达及作用,阐明PEDF基因转染对巨噬细胞诱导的鼠增生性玻璃体视网膜病变的抑制作用。方法：采用阳离子脂质体包裹pcDNA3-PEDF,注射到36只SD大鼠玻璃体腔内（每组大鼠的右眼为实验眼,左眼作为阴性对照眼）,大鼠分为PVR对照组(仅在玻璃体腔内注射巨噬细胞诱发PVR形成)、盐水对照组（在玻璃体腔内注射生理盐水3 d后注射巨噬细胞）和转染组（在玻璃体腔内注射脂质体、pcDNA3-PEDF混合物,3 d后注射巨噬细胞）,每组12只,应用检眼镜和全视网膜镜观察各组大鼠玻璃体和视网膜情况;HE染色光镜下观察各组大鼠玻璃体、视网膜各层结构和细胞增殖情况。结果：检眼镜和全视网膜镜观察各组大鼠PVR形成情况,玻璃体腔注射巨噬细胞后,与转染组比较,PVR对照组和盐水对照组大鼠可见玻璃体腔内增殖明显。于注射后1周见PVR对照组和盐水对照组开始出现条索样增殖,2～3周时增殖逐渐加重,并开始出现视网膜隆起,4周见全部模型眼均有明显增殖改变,有条索状增殖物牵引网膜,并出现牵拉网脱;转染组大鼠中仅1眼见玻璃体牵拉,视网膜浅脱离,余眼玻璃体无明显混浊,眼底清晰,视网膜平伏。HE染色,转染组大鼠绝大部分实验眼视网膜各层细胞结构清晰,仅发生了视网膜浅脱离的1眼可见视网膜前增殖膜,伴少量炎性细胞浸润;PVR对照组和盐水对照组大鼠玻璃体腔内可见随病程进展的炎症反应,炎症细胞聚集、成纤维细胞增殖、瘢痕形成最终导致眼球萎缩。结论：大鼠玻璃体腔注射转染PEDF可以明显抑制巨噬细胞诱导的PVR形成和发展。     

SOX-9真核表达质粒转染兔骨髓基质细胞

目的探讨SOX(sry-type high-mobility-group box)-9基因转染兔骨髓基质细胞的方法及可行性。方法构建SOX-9基因真核表达质粒,用脂质体法介导转染兔骨髓基质细胞,通过形态学观察、免疫组织化学、酶联免疫吸附法及反转录-聚合酶链反应检测SOX-9基因转染兔骨髓基质细胞的成功性,以及转染后骨髓基质干细胞的生物学特性。结果免疫组织化学检测实验组细胞内有稳定的SOX-9表达,在2周的表达量高于6d的表达量。RT-PCR结果表明只有实验组有SOX-9的基因表达。酶联免疫吸附法检测结果显示各时间点SOX-9的基因表达实验组均明显高于其余2组(P<0.01),实验组表达量48h时达到最高。结论SOX-9基因可以转染兔骨髓基质干细胞,并能诱导骨髓基质干细胞向成软骨方向分化。     

巨噬细胞集落刺激因子及其受体参与感染性心内膜炎发病的实验研究

目的研究巨噬细胞集落刺激因子及其受体(M-CSF/c-fms)在单核/巨噬细胞参与感染性心内膜炎(IE)发生过程中的生物学作用。方法两种剂量金黄色葡萄球菌注射联合手术损伤心脏瓣膜的方法分别建立4组IE家兔模型;术后24 h处死,取出心脏瓣膜,肉眼、电镜观察。RT-PCR法检测各组瓣膜的M-CSF、c-fms mRNA表达水平。结果32例动物中存活26例,14例发生IE;小剂量组中赘生物产生、细菌培养阳性率显著低于大剂量组(P<0.05);手术+细菌注射可诱导二尖瓣、三尖瓣M-CSF mRNA表达明显增加(P<0.05),c-fms mRNA表达明显降低(P<0.05);大剂量细菌注射比小剂量细菌注射可诱导二尖瓣M-CSF mRNA表达进一步明显增加(P<0.01),三尖瓣差异无显著性(P>0.05)。结论M-CSF/c-fms是参与IE发生的重要因子之一;左、右心腔对大剂量细菌入侵有不同的抗感染免疫反应,也是左、右心IE有不同临床特点的原因之一。