孕中晚期咖啡因暴露对胎鼠宫内发育的影响及其胎盘损伤机制

目的：建立孕中晚期咖啡因暴露的大鼠宫内发育迟缓（IUGR）模型，观察咖啡因对胎鼠生长发育的影响，并探讨其胎盘损伤机制。方法：成年Wistar大鼠雌雄2：1合笼受孕，孕鼠随机分为四组，于孕第12天咖啡因灌胃（20、60和180mg·kg^-1·d^-1），对照组给予等体积蒸馏水，孕第21天处死孕鼠，颈动脉取血，记录各组胎仔的体重、身长、尾长和胎盘重量。透射电镜观察胎盘超微结构改变，放免法测定孕鼠血浆血管紧张素Ⅱ（AngⅡ）浓度，RT—PCR检测胎盘血管紧张素受体ATI和AT2表达水平。结果：与对照组比较，咖啡因组胎仔体重、身长、尾长和胎盘重量均明显降低（P〈0．01），且呈剂量依赖性；中、大剂量组IUGR发生率明显升高，分别为19．6％和60．4％（P〈0．01）。透射电镜下见咖啡因大剂量组胎盘绒毛血管数量明显减少，管腔狭窄，滋养层细胞间间距缩小，细胞损伤明显。孕鼠血中AngⅡ浓度高于对照组，尤以大剂量组明显（F〈0．01）。胎盘组织AT2的mRNA表达呈上升趋势，而AT1无显著变化。结论：孕中晚期咖啡因暴露叮明显影响胎鼠的宫内发育，提高IUGR发生率。     

三七总苷对糖尿病肾病模型大鼠血管内皮生长因子及骨形成蛋白-7的影响

目的 通过观察三七总苷（PNS）对糖尿病肾病大鼠肾脏中血管内皮生长因子（VEGF）和骨形成蛋白-7（BMP-7）表达的影响,探讨PNS防治糖尿病肾病的作用及机制。方法选用雄性SD大鼠50只,随机分为正常组（N组），糖尿病模型组（DM组），三七总苷低、高剂量组（PNS-L组、PNS-H组）和卡托普利组（C组），每组10只。DM组、PNS-L、PNS H和C组采用尾静脉注射链脲佐菌素（STZ）法建立1型糖尿病大鼠模型，PNS-L、PNS-H组分别予PNS 100和200 mg·kg-1·d-1灌胃, C组给予卡托普利50 mg·kg-1·d-1灌胃，N组与DM组给予等量双蒸纯化水灌胃。4周后测定各组大鼠空腹血糖（FBG）和24 h尿微量清蛋白；采用免疫组织化学方法检测大鼠肾组织中VEGF和BMP 7。结果DM组大鼠FBG、24 h尿微量清蛋白及VEGF表达明显升高,BMP-7表达明显降低；PNS H组BMP-7表达明显升高，其他各项指标均明显降低。结论PNS能有效防治糖尿病肾病，其机制可能与降低VEGF及升高BMP-7有关。     

维A酸对大鼠胃癌前病变胃黏膜 PCNA、 VEGF和Bcl-2 表达的影响

目的观察维A酸（RA）对大鼠胃癌前病变胃黏膜增殖细胞核抗原（PCNA）、血管内皮生长因子(VEGF)和凋亡抑制因子 2(Bcl 2)表达的影响。方法采用甲硝基亚硝基胍（MNNG）、0.03%雷尼替丁、56 ℃15%氯化钠溶液、0.85%脱氧胆酸钠、40%乙醇、饥饱失常等多种因素制作大鼠胃癌前病变模型，分别给予不同剂量维A酸（20和40 mg·kg 1）灌胃治疗；另一组模型大鼠不给予治疗，设为自然恢复组。采用免疫组化方法检测各组大鼠胃黏膜PCNA（以增殖指数 PI表示）、VEGF和Bcl 2蛋白表达水平。结果正常对照大鼠和维A酸不同剂量组大鼠胃黏膜PI、VEGF和Bcl 2蛋白阳性率均较自然恢复组低（P＜0.01或P＜0.05）。结论维A酸可能通过下调PCNA、VEGF和Bcl 2蛋白表达而抑制细胞增殖和诱导细胞凋亡，进而发挥治疗大鼠胃癌前病变的作用。     

高原地区胎盘VEGF在胎儿生长受限和巨大儿中的表达及意义

目的血管内皮生长因子(VEGF)是一种对血管内皮细胞有特异高效的促有丝分裂因子,通过检测血管内皮生长因子在胎盘母面和子面的水平,探索胎儿生长受限和巨大儿的发病因素和发生的机制。方法随机选择2010年1月至2011年2月在青海省妇女儿童医院足月分娩的足月小样儿(体重<2 500g的新生儿)50例产妇为宫内发育受限组,选择同期分娩体重≥4 000g新生儿50例产妇为巨大儿组;采用免疫组化链霉菌抗生物素蛋白-过氧化酶连接法(SP法)检测巨大儿(对照组)和胎儿生长受限患者(IUGR组)胎盘组织中VEGF的表达;巨大儿和IUGR组均为初产妇,两组孕妇年龄、孕周及体质量差异无显著性。结果胎儿生长受限患者胎盘组织中VEGF阳性表达率低于巨大儿组,两者差异有统计学意义(P<0.05)。结论 IUGR患者胎盘VEGF水平下降,可能是胎儿生长受限发病机理中的一个重要因素。     

血管内皮生长因子联合地塞米松对胎鼠肺泡Ⅱ型细胞的影响

目的研究联合使用血管内皮生长因子(VEGF)和地塞米松对胎鼠肺泡Ⅱ型细胞发育和肺泡表面活性物质结合蛋白B(SP-B)表达的影响，为防治早产儿呼吸窘迫综合征寻找新途径。方法取孕20 d的Wistar大鼠剖腹取胎鼠，原代培养肺泡Ⅱ型细胞，将所得肺泡Ⅱ型细胞分成4组，分别加入VEGF、地塞米松、VEGF＋地塞米松、空白培养液(即对照组)，孵育后测定各组胎鼠肺泡Ⅱ型细胞VEGF及其受体Flt-1、Flk-1和SP-B。结果VEGF组、地塞米松组与VEGF＋地塞米松组SP-B均阳性表达，对照组SP-B阴性表达；VEGF组与VEGF＋地塞米松组VEGF、Flt-1、Flk-1阳性表达，地塞米松组VEGF、Flt-1、Flk-1阴性表达。结论VEGF能促进肺泡发育和肺表面活性物质SP-B的合成与分泌，拮抗地塞米松下调肺泡Ⅱ型细胞受体表达的作用。     

沙利度胺抑制血管内皮生长因子表达对肝细胞癌变的影响

目的动态观察沙利度胺对血管内皮生长因子（VEGF）表达干预对肝细胞癌变的影响。方法将SD大鼠分为诱癌组、诱癌干预组和正常对照组进行动态观察VEGF的表达。诱癌组及诱癌干预组以含2-乙酰氨基芴（2-FAA,0．05％）的颗粒饲料喂饲诱发肝癌。诱癌干预组同时以沙利度胺（100mg/kg体重）灌胃。诱癌鼠及诱癌干预鼠每两周处死一组。并以正常鼠作对照。以病理组织学（HE染色）观察肝细胞形态学变化、免疫组织化学和EHSA法分析VEGF表达变化。结果诱癌组肝细胞出现颗粒样变性、不典型增生、大量癌巢结节,而诱癌干预组形态变化明显受抑;正常肝仅有较低水平VEGF表达,诱癌组肝VEGF表达进行性增加,与肝组织学改变一致,显著高于正常组：在诱癌干预组VEGF表达则显著低于诱癌组的同期水平：且癌变干预组鼠肝癌发生率明显低于诱癌组。结论沙利度胺抑制肝VEGF表达、可推迟肝细胞癌变的发生。     

非那雄胺对前列腺组织血管内皮生长因子的影响

目的建立SD大鼠前列腺增生模型,探讨非那雄胺对大鼠前列腺组织血管内皮生长因子(VEGF)的影响。方法雄性SD大鼠40只,隔日于颈部皮下注射丙酸睾丸酮(连续28d),建立大鼠前列腺增生模型,之后将大鼠随机分为5组:A组灌胃给予安慰剂,B、C、D、E组灌胃给予非那雄胺,持续时间分别1、2、3、4周。采用免疫组织化学法检测大鼠前列腺组织中VEGF的表达。结果A组前列腺组织中VEGF的表达明显高于B、C、D、E组,差异有统计学意义(P<0.05);B组前列腺组织中VEGF的表达高于D、E组,差异有统计学意义(P<0.05);C组前列腺组织VEGF的表达高于D、E组,差异有统计学意义(P<0.05);B组与C组、D组与E组之间比较差异无统计学意义(P>0.05)。结论非那雄胺可以抑制大鼠前列腺组织中VEGF的表达,并且其抑制程度与非那雄胺的作用时间有关。     

沃丽汀对糖尿病肾病大鼠CGRP与VEGF的影响

目的观察沃丽汀对糖尿病肾病大鼠肾脏的保护作用，并探讨其作用机制。方法将雄性Wistar大鼠随机分为正常对照组（NC组），糖尿病肾病组（DN组）和沃丽汀治疗组（D＋J组）各10只。DN组与D＋J组采用链脲佐菌素（STZ）诱导制作糖尿病大鼠模型。模型制作成功后，NC组与DN组给予0.9%氯化钠溶液10 mL&#8226;kg 1灌胃，D＋J组于模型制作成功后第3天开始给予沃丽汀灌胃，0.9 mg&#8226;kg 1&#8226;d 1。8周后采用放免法检测大鼠血浆降钙素基因相关肽（CGRP）含量，免疫组织化学方法检测肾小球血管内皮生长因子（VEGF）表达情况，同时检测24 h尿清蛋白排泄率（24 hUAER）、尿肌酐清除率（Ccr）、肾重指数（KMI）、体重及血糖。结果与NC组比较，DN组血浆中CGRP水平、Ccr及体重均显著降低（均P＜0.01），24 hUAER、KMI、肾脏VEGF表达及血糖均显著升高（均P＜0.01）。与DN组比较，D＋J组CGRP水平差异无显著性，Ccr显著升高（P＜0.05），肾脏VEGF表达显著降低（P＜0.01）。结论沃丽汀对糖尿病肾病大鼠血浆CGRP水平无显著影响，但能抑制肾组织VEGF表达，一定程度上延缓糖尿病肾病发展。     

邻苯二甲酸二乙基己基酯对胎鼠肺发育的抑制作用

目的探讨孕大鼠染毒邻苯二甲酸二乙基己基酯(DEHP)对胎鼠肺发育的抑制作用及其可能机制。方法 Sprague-Dawley大鼠受孕后第12天每天ig给予DEHP0,10,100和750mg.kg-1,至自然分娩。第1天每窝随机取自然分娩仔鼠3只,测定体质量;光镜观察肺组织病理学改变及测定辐射状肺泡计数(RAC)和肺间质比例,免疫组化法检测基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶组织抑制剂-2(TIMP-2)和血管内皮生长因子(VEGF)的表达。结果与正常对照组相比,DEHP组仔鼠体质量明显下降(P<0.01)。光镜下仅DEHP750mg.kg-1组可见肺间质增厚,间质细胞增多,肺泡数目减少,RAC减小,肺间质比例增大(P<0.05)。与正常对照组比较,DEHP组VEGF表达差异无统计学意义;DEHP10,100和750mg.kg-1组MMP-2表达和MMP-2/TIMP-2值明显高于正常对照组〔MMP-2分别为0.099±0.009,0.124±0.008,0.140±0.010vs0.091±0.011(P<0.01);MMP-2/TIMP-2分别为1.079±0.074,1.447±0.077,1.704±0.084vs0.994±0.079(P<0.01)〕。结论孕鼠染毒DEHP后对胚胎生长和肺发育有抑制作用。DEHP抑制胎鼠肺发育的机制可能与MMP-2的过度表达以及MMP-2/TIMP-2平衡失调有关。     

健胎液对胚泡着床障碍大鼠子宫血管生成作用的影响

［摘要］目的观察健胎液对胚泡着床障碍大鼠胚泡着床的影响,并探讨其作用机制。方法早孕大鼠随机分为正常组、模型组及中药组（健胎液组）,观察妊娠第8天各组大鼠妊娠率及平均着床胚泡数;逆转录 聚合酶链反应（RT PCR）法检测妊娠第5～第8天各组子宫内膜环氧化酶 2（COX 2）和血管内皮细胞生长因子（VEGF）基因表达的差异;放射免疫法检测妊娠第5～8天各组子宫内膜中6 酮 前列腺素F1α（6 keto PGF1α）的水平。 结果中药组妊娠率及平均着床胚泡数均较模型组显著提高（P＜0.05或P＜0.01）;模型组子宫内膜COX 2 mRNA、VEGF mRNA及6 keto PGF1α表达水平均低于正常组及中药组（P＜0.05或P＜0.01）。结论健胎液通过上调胚泡着床障碍大鼠子宫内膜COX 2、VEGF及6 keto PGF1α表达,促进子宫内膜血管增殖,改善子宫内膜的发育,利于胚泡着床。     

Altered matrix metalloproteinase-2 and -9 expression/activity links placental ischemia and anti-angiogenic sFlt-1 to uteroplacental and vascular remodeling and collagen deposition in hypertensive pregnancy

Preeclampsia is a complication of pregnancy manifested as maternal hypertension and often fetal growth restriction. Placental ischemia could be an initiating event, but the linking mechanisms leading to hypertension and growth restriction are unclear. We have shown an upregulation of matrix metalloproteinases (MMPs) during normal pregnancy (Norm-Preg). To test the role of MMPs in hypertensive-pregnancy (HTN-Preg), maternal and fetal parameters, MMPs expression, activity and distribution, and collagen and elastin content were measured in uterus, placenta and aorta of Norm-Preg rats and in rat model of reduced uteroplacental perfusion pressure (RUPP). Maternal blood pressure was higher, and uterine, placental and aortic weight, and the litter size and pup weight were less in RUPP than Norm-Preg rats. Western blots and gelatin zymography revealed decreases in amount and gelatinase activity of MMP-2 and MMP-9 in uterus, placenta and aorta of RUPP compared with Norm-Preg rats. Immunohistochemistry confirmed reduced MMPs in uterus, placenta and aortic media of RUPP rats. Collagen, but not elastin, was more abundant in uterus, placenta and aorta of RUPP than Norm-Preg rats. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) decreased MMPs in uterus, placenta and aorta of Norm-Preg rats, and vascular endothelial growth factor (VEGF) reversed the decreases in MMPs in tissues of RUPP rats. Thus placental ischemia and anti-angiogenic sFlt-1 decrease uterine, placental and vascular MMP-2 and MMP-9, leading to increased uteroplacental and vascular collagen, and growth-restrictive remodeling in HTN-Preg. Angiogenic factors and MMP activators may reverse the decrease in MMPs and enhance growth-permissive remodeling in preeclampsia.     

沙利度胺联合孕三烯酮对大鼠子宫内膜异位症血管生成的影响

目的探讨沙利度胺、孕三烯酮及两者联合用药对大鼠子宫内膜异位组织中血管生成的影响。方法24只子宫内膜异位症模型SD大鼠,随机分为模型对照、沙利度胺(20mg·kg-1·d-1)、孕三烯酮(0.5mg·kg-1·d-1)及联合用药(沙利度胺20mg·kg-1·d-1和孕三烯酮0.5mg·kg-1·d-1)4组,每组6只。药物溶于生理盐水中腹腔注射给药,模型对照组每日腹腔注射生理盐水2mL。给药4wk后处死,免疫组织化学SP法测定血管内皮生长因子(VEGF)和肿瘤坏死因子α(TNF-α)在异位内膜的表达,并通过Ⅷ因子标记异位子宫内膜血管,检测异位内膜组织中微血管密度(MVD)。结果沙利度胺组、孕三烯酮组及联合用药组异位内膜MVD、VEGF和TNF-α的表达均显著低于模型对照组(P<0.01),其中联合用药组MVD和VEGF比沙利度胺组和孕三烯酮组降低得更为显著(P<0.05),联合用药组TNF-α与孕三烯酮组无显著差异(P>0.05)。结论沙利度胺和孕三烯酮可抑制大鼠异位内膜的MVD、VEGF和TNF-α的表达,从而抑制子宫内膜异位症血管生成,当两者联合用药时,作用更强。     

Effects of KRN633, an Inhibitor of Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase,on Vascular Development of Placenta and Fetus of Mid Pregnancy in Mice

Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway during pregnancy contributes to several pathologic pregnancies, such as hypertension, preeclampsia, and intrauterine growth restriction, but its effects on the fetus have not been fully examined. To determine how inhibition of the VEGF signaling pathway affects the fetal vascular development of mid pregnancy, we treated pregnant mice daily with either the VEGF receptor-2 (VEGFR-2) tyrosine kinase inhibitor KRN633 (300 mg/kg, p.o.) or the vehicle from 13.5 to 15.5 day of pregnancy. On the 16.5 day of pregnancy, the vascular beds in the placenta and several organs of the fetus were visualized by fluorescent immunohistochemistry. All mice treated with KRN633 appeared healthy, and total numbers of fetuses per litter were unaffected. However, weights of the placenta and fetus from KRN633-treated mice were lower than those from the vehicle-treated ones. No external malformations and bleeding were observed in the placenta and fetus, whereas immunohistochemical analyses revealed that the vascular development in labyrinthine zone of placenta and fetal organs examined (skin, pancreas, kidney, and lung) were impaired by KRN633 treatment. These results suggest that inhibition of the VEGF signaling pathway during mid pregnancy suppresses vascular growth of both the placenta and fetus without obvious health impairments of mother mice and increases the risk of induction of intrauterine growth restriction.     

Enhancement of placental antioxidative function and P-gp expression by sodium ferulate mediated its protective effect on rat IUGR induced by prenatal tobacco/alcohol exposure

This study was aimed to explore the therapeutic effect of sodium ferulate (SF) on rats with intrauterine growth retardation (IUGR), and then to clarify the corresponding mechanism. Pregnant rats were divided into normal group, tobacco/alcohol exposure group, and tobacco/alcohol+SF groups. Fetal developmental indices, placental weight, histological alteration, oxidative and antioxidative-function (e.g. MDA, SOD, CAT) and Mdr1 levels were assayed. Results showed exposure to tobacco/alcohol resulted in reduced fetal developmental indices and placental histological alteration, as well as the increased MDA content, decreased SOD and CAT activities and decreased Mdr1a level. After SF treatment, fetal developmental indices, and placental weight, histological alteration, oxidative and antioxidative-function and mdr1a levels were reversed. Our study indicated SF may be effective in reversing IUGR production, and its underlying mechanism may be due to enhanced placental antioxidative function and P-gp expression, which may be related to IUGR formation by tobacco/alcohol exposure.     

Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor

Preeclampsia is a complication affecting pregnant women worldwide, which leads to maternal and fetal morbidity and mortality. In this study, we evaluated the efficacy of ferulic acid (FA) on an N^ω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME) induced rat model of preeclampsia. L‐NAME was administered to pregnant rats to induce preeclampsia. 48 rats were divided into three experimental groups (n=16 each): control group, preeclampsia group and preeclampsia with FA treatment (preeclampsia+FA). Physiological characteristics such as urine volume, total urine protein and blood pressure were assessed. Expressions levels of urinary nephrin and podocin mRNAs were analyzed by RT‐PCR. Levels of renal vascular endothelial growth factor (VEGF), renal soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and serum placenta growth factor (PlGF) were also examined. Urine volume, total urine protein and blood pressure were markedly increased in preeclampsia group rats compared to control (P<.05), which were then significantly reduced in preeclampsia+FA group (P<.05). Expressions of urinary nephrin and podocin mRNAs, levels of VEGF, sFlt‐1 and PlGF were also reversed in preeclampsia+FA group compared to preeclampsia rats (P<.05). We hereby report for the first time, FA alleviates preeclampsia symptoms in a rat preeclampsia model, supporting its potential value in treating preeclampsia.     

当归注射液对烟酒所致大鼠宫内发育迟缓的拮抗作用及机制

目的 :了解烟酒所致胎儿宫内发育迟缓 (IU GR)时孕鼠胎盘组织抗氧化功能的改变 ,探讨当归注射液的保护作用及机制。方法 :采用烟酒混合因素建立大鼠IUGR模型 ,部分孕鼠给予当归注射液0 .2 5g·kg-1治疗 ,测定胎盘组织中还原型谷胱甘肽(GSH)和丙二醛 (MDA)的含量及超氧化物歧化酶(SOD)、过氧化氢酶 (Cat)和谷胱甘肽过氧化物酶(GSH Px)的活性。结果 :IUGR孕鼠胎盘组织MDA和GSH含量均明显增加 (P <0 .0 1,P <0 .0 5 ) ,SOD、GSH Px和Cat活性显著下降 (P <0 .0 1,P <0 .0 5 )。经当归注射液治疗后 ,胎儿宫内生长发育接近正常 ,上述指标也得到改善。结论 :胎盘氧化损伤可能是IUGR发病的一个重要机制。当归注射液能提高IUGR孕鼠胎盘的抗氧化能力 ,促进胎儿宫内生长发育。     

减少奥卡西平对妊娠小鼠不良作用的实验研究

摘要目的观察奥卡西平单次给药与分次给药对妊娠小鼠的影响及叶酸对其诱发小鼠发生妊娠意外的干预效果,探讨减少奥卡西平所致不良作用的干预措施。方法将150只小鼠随机分为5组（每组30只,雌雄比例2：1）,分别为：①对照组（灌胃纯化水10 mL&#8226;kg－1）,②奥卡西平单次给药组（单次灌胃奥卡西平150 mg&#8226;kg－1）,③奥卡西平单次给药＋叶酸组（单次灌胃奥卡西平150 mg&#8226;kg－1 ＋叶酸0.07 mg&#8226;kg－1）,④奥卡西平分次给药组（分次灌胃奥卡西平,上、下午各75 mg&#8226;kg－1）,⑤奥卡西平分次给药＋叶酸组（分次灌胃奥卡西平,上、下午各75 mg&#8226;kg－1 ＋叶酸0.07 mg&#8226;kg－1）。观察小鼠受孕率、流产率、死胎吸收胎率、畸形率、每窝正常仔鼠的数目、妊娠期增重、小鼠血清叶酸含量等指标。结果奥卡西平单次给药组、单次给药＋叶酸组、分次给药组、分次给药＋叶酸组小鼠受孕分别为4,6,8,10只;死胎和吸收胎分别为3,4,5,6只;小鼠妊娠期增重、血清叶酸含量依次升高;奥卡西平无明显致畸作用。结论奥卡西平可导致妊娠小鼠妊娠意外的增加,但无明显致畸作用,小剂量分次给药及补充适量叶酸可降低其不良作用。     

代谢综合征幼鼠血管VEGF和vWF的表达及意义

目的:探讨血管内皮生长因子(VEGF)和血管性假血友病因子(vWF)在代谢综合征(MS)幼鼠血管壁和血清中的表达及意义.方法:3周龄SD大鼠随机分为普通饮食组(NC组)、高脂组(FC组)和高脂+高盐组(FSC组).实验4周末测体质量、腹围、血压、内脏脂肪质量、血脂,行口服葡萄糖耐量试验,计算胰岛素抵抗指数.取腹主动脉免疫组化法检测血管壁VEGF和vWF表达,ELISA方法检测血清VEGF和vWF表达.结果:FSC组体质量、腹围、血压、内脏脂肪、血糖、胰岛素水平均较NC组增加,血脂紊乱加重,并出现胰岛素抵抗.FC组仅体质量、内脏脂肪质量高于NC 组,其他上述指标差异无统计学意义.FSC组血管壁及血清中VEGF和vWF较NC组和FC组均升高.FC组较NC组血管VEGF及血清中VEGF和vWF均升高.结论:VEGF和vWF参与了血管壁的功能紊乱或损伤的病生理改变.     

多肽调控因子AcSDKP对单侧输尿管梗阻大鼠肾间质纤维化的抑制作用

目的:观察N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)对单侧输尿管梗阻(UUO)所致大鼠肾间质纤维化的抑制作用并初探其机制。方法:将18只大鼠随机均分为假手术组(生理盐水)、模型组(生理盐水)、治疗组(400μg·kg-1AcSD-KP),皮下注射给药1d(每天2次)后,后2组建立UUO模型,各组给药至造模后第14天处死大鼠,观察各组肾组织病理改变,检测肾组织转化生长因子β(1TGF-β1)、血管内皮生长因子(VEGF)蛋白及二者mRNA的表达。结果:与假手术组比较,模型组和治疗组大鼠肾小管变性及肾间质纤维化程度严重(P<0.05),TGF-β1及其mRNA表达水平明显增强(P<0.05),VEGF蛋白及其mRNA表达水平明显减弱(P<0.05);与模型组比较,治疗组大鼠肾小管变性及肾间质纤维化程度明显改善(P<0.05),TGF-β1及其mRNA表达水平明显减弱(P<0.05),VEGF蛋白及其mRNA表达水平明显增强(P<0.05)。结论:AcSDKP可能通过减弱TGF-β1、增强VEGF的表达以达到抑制肾间质纤维化的作用。