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1.
目的分析同源盒基因Meox1在心肌梗死大鼠心肌中的表达情况。方法清洁级雄性SD大鼠20只,随机分入心肌梗死组和假手术组,每组10只。心肌梗死组采用结扎左冠状动脉前降支构建心肌梗死模型,手术过程死亡2只。假手术组仅穿线不结扎。术后7 d处死大鼠,制作石蜡切片,HE染色以及Masson染色观察心肌组织变化,免疫组化法检测Meox1的表达水平。结果 HE染色结果:心肌梗死组可见梗死区心肌细胞显著减少,核碎裂,核消失,被大量排列紊乱的结缔组织代替,可见大量粒细胞、单核细胞浸润。梗死边缘区可见心肌细胞代偿性肥大,横纹模糊或消失,心肌间隙水肿增宽,部分心肌纤维溶解、断裂,可见炎性细胞浸润、成纤维细胞增生。梗死远离区及假手术组大鼠心肌形态正常,结构清晰,心肌纤维排列整齐。Masson染色结果,非梗死区染色呈红色为正常心肌组织,蓝色为胶原纤维。假手术组及梗死远离区心肌细胞排列整齐紧密,细胞间隙散在分布少量胶原纤维;心肌梗死组梗死区可见细胞间隙大量胶原纤维沉积,梗死边缘区的细胞间隙也有大量的胶原纤维沉积。免疫组化结果,梗死区及梗死边缘区的心肌细胞中可见棕黄色颗粒沉积,有Meox1表达;在梗死远离区的正常心肌细胞中未见Meox1的表达;假手术组心肌细胞中亦未见Meox1的表达。假手术组及梗死远离区毛细血管内皮细胞中未见Meox1的表达;心肌梗死组梗死区及梗死边缘区毛细血管内皮细胞中Mexo1表达不明显。结论在心肌梗死大鼠心肌组织中Meox1表达增高,提示其可能参与心肌梗死后心肌重塑。  相似文献   

2.
目的探讨慢病毒介导的胸腺肽β4基因经梗死区直接注射对大鼠急性心肌梗死后心功能的影响。方法雄性SD大鼠32只,随机分为4组,每组8只。假手术组:开胸+不结扎冠状动脉,心肌内分五点注射生理盐水50μl;生理盐水组:开胸+冠状动脉左前降支结扎,梗死区心肌内注射等量生理盐水50μl;胸腺肽β4组:开胸+冠状动脉左前降支结扎,梗死区心肌内注射pGC-FU-胸腺肽β4 50μl;空载病毒组:开胸+冠状动脉左前降支结扎,梗死区心肌内注射空载病毒50μl。4周后,大鼠心脏超声测定心功能,Western blot法检测胸腺肽β4和血管内皮生长因子蛋白的表达,RT-PCR法检测胸腺肽β4基因的表达。结果胸腺肽β4组LVEF较生理盐水组和空载病毒组明显提高(P<0.01)。胸腺肽β4组心肌组织中胸腺肽β4和血管内皮生长因子蛋白表达较假手术组、生理盐水组和空载病毒组明显增加,差异有统计学意义(P<0.05)。结论经梗死区直接注射慢病毒载体携带的胸腺肽β4基因可以改善心肌梗死后的心功能。  相似文献   

3.
目的 通过建立大鼠心肌梗死模型,观察急性心肌梗死对大鼠心脏内皮型一氧化氮合酶mRNA和诱导型一氧化氮合酶蛋白表达的影响。方法48只健康成年SD大鼠(体重200~250g)随机分为假手术组和缺血组,取1、2、8和24h四个不同时间点观察。采用开胸结扎冠状动脉左前降支建立心肌缺血模型,逆转录聚合酶链反应检测大鼠心肌梗死后1、2及24h三个时段缺血心肌内皮型一氧化氮合酶mRNA的表达;免疫组织化学染色检测冠状动脉结扎后8h缺血心肌诱导型一氧化氮合酶蛋白的表达。结果冠状动脉结扎后2h,缺血组大鼠缺血心肌组织内皮型一氧化氮合酶mRNA表达下降(P〈0.05),并持续至结扎后24h;结扎后24h组内皮型一氧化氮mRNA的表达与结扎后2h组相比无显著性差异(P〉0.05)。冠状动脉结扎后8h,梗死区存活心肌组织细胞诱导型一氧化氮合酶蛋白大量表达,而假手术组未见诱导型一氧化氮合酶蛋白表达。结论正常大鼠心肌组织有内皮型一氧化氮合酶基因表达,无诱导型一氧化氮合酶蛋白表达。在心肌梗死早期缺血心肌内皮型一氧化氮合酶mRNA表达减少。心肌急性缺血刺激早期诱导大鼠缺血心肌组织诱导型一氧化氮合酶蛋白大量表达。  相似文献   

4.
目的 观察诱生型一氧化氮合酶(inducible nitric oxide sythase,iNOS)蛋白在心肌梗死后早期大鼠心脏的表达变化.方法 将12只大鼠随机分为心肌梗死组和假手术组.采用开胸结扎冠状动脉左前降支的方法建立心肌缺血模型,用免疫组织化学方法检测大鼠心肌梗死后24 h缺血心脏iNOS蛋白颗粒的表达.结果 在大鼠冠状动脉结扎后24h,梗死周围区心肌组织细胞出现大量iNOS蛋白表达,与假手术组相比差异有统计学意义(P<0.01)假手术组未见iNOS蛋白表达.结论 正常心肌组织无iNOS蛋白表达,心肌梗死后早期缺血心肌组织检测到大量iNOS蛋白表达.  相似文献   

5.
目的 了解急性心肌梗死后梗死周边区心肌组织中HCN2和HCN4的mRNA和蛋白表达的动态变化.方法 通过结扎大鼠左冠状动脉前降支建立急性心肌梗死模型,将成功建模的大鼠随机分为24 h组、1周组、2周组和4周组,同时于各时间点均设立假手术组,每组5只.于各时间点末取左心室梗死周边区心肌组织样本(假手术组取左心室相应部位的心肌组织),用逆转录聚合酶链反应检测HCN2和HCN4 mRNA的表达,用免疫组织化学和免疫印迹法检测HCN2和HCN4蛋白的表达.结果 假手术组左心室心肌组织中存在HCN2和HCN4通道蛋白的表达,梗死周边区心肌组织中HCN2和HCN4的表达在梗死后24 h出现上升趋势,于梗死后1周表达达到峰值,之后逐渐下降,梗死后4周HCN2 mRNA和蛋白的表达仍高于对照组,而HCN4的表达已回落至假手术组水平.结论 急性心肌梗死后左心室梗死周边缺血区心肌组织HCN2和HCN4通道蛋白的表达呈动态变化趋势,梗死后1周表达明显增高.  相似文献   

6.
目的观察己酮可可碱对老年雄性大鼠心肌梗死后梗死面积、心功能及基质金属蛋白酶(MMP)-9蛋白在心肌中表达的影响。方法45只老年雄性Wistar大鼠,随机分为假手术组、模型组、治疗组,每组15只。假手术组,开胸暴露心脏,只穿线而不结扎左冠状动脉前降支,模型组和治疗组分别结扎左冠状动脉前降支。治疗组术后即刻及术后每天腹腔注射己酮可可碱,假手术组和模型组注射等剂量生理盐水。术后7 d分别取材,进行心肌梗死面积测定、通过小动物多道生理记录仪和超声心动图检测心功能、免疫组化法观察MMP-9的蛋白表达情况。结果治疗组心肌梗死面积缩小、心功能改善明显;与假手术组相比,模型组和治疗组MMP-9蛋白表达显著升高;治疗组MMP-9蛋白表达水平低于模型组。结论己酮可可碱对老年大鼠缺血心肌具有保护作用,其机制可能是减少MMP-9蛋白的表达。  相似文献   

7.
目的探讨犬急性心肌梗死后梗死相关血管晚期再灌注对梗死周边缺血区心肌细胞凋亡以及凋亡相关基因bcl-2、bax及其相关蛋白表达的影响。方法健康成年杂交犬28只,全身麻醉下常规开胸暴露冠状动脉后随机分为三组:假手术组(n=8)、急性心肌梗死组(n=10)和晚期再灌注组(n=10)。假手术组仅行左冠状动脉前降支下穿过丝线而不结扎冠状动脉,急性心肌梗死组行左冠状动脉前降支高位永久结扎,晚期再灌注组在高位结扎左冠状动脉前降支6 h后松解结扎线予以6 h的再灌注处理。共有23只犬模型制作成功。各组犬均于术后12 h处死,采集心肌标本。使用脱氧核糖核苷酸末端转移酶介导的原位缺口末端标记法检测心肌细胞凋亡,逆转录聚合酶链反应法检测心肌细胞bcl-2和bax mRNA表达水平,免疫组织化学染色和蛋白印迹法分析bcl-2、bax在心肌细胞中的表达情况。结果晚期再灌注组心肌细胞凋亡指数较急性心肌梗死组明显减少(P<0.05),且两组心肌细胞凋亡指数均高于假手术组(P<0.01)。急性心肌梗死组和晚期再灌注组bcl-2和bax mRNA的表达均明显高于假手术组(P<0.01),且晚期再灌注组bax mRNA的表达明显低于急性心肌梗死组(P<0.05),而bcl-2 mRNA两组间差异无显著性。与假手术组相比,急性心肌梗死组和晚期再灌注组bcl-2蛋白的表达均明显升高(P<0.01),其中在晚期再灌注组的表达略高于急性心肌梗死组,但差异无显著性;晚期再灌注组bax蛋白的表达明显高于假手术组(P<0.01),但明显低于急性心肌梗死组(P<0.05)。结论急性心肌梗死后晚期再灌注可以减少梗死周边缺血区心肌细胞凋亡,其机制可能与心肌细胞bax基因及其相应的蛋白表达减少有关。  相似文献   

8.
目的研究积雪草苷对心肌梗死大鼠左室心肌纤维化和心肌组织转化生长因子(TGF)-β1、Ⅰ型胶原(Col)Ⅰ和Ⅲ型胶原(col)Ⅲ表达的影响。方法结扎雄性SD大鼠大鼠左冠状动脉前降支建立心肌梗死模型,随机分为假手术组、假手术+积雪草苷组、心肌梗死模型组和心肌梗死模型+积雪草苷组。造模当天给药,早晚各1次,2 w后分别测定各组大鼠心脏左心室重量与体重之比、左室梗死面积;免疫组织化学检测心肌组织非梗死区TGF-β1、ColⅠ、ColⅢ的表达。结果心肌梗死模型组和心肌梗死模型+积雪草苷组左室梗死面积无显著差异(P0.05)。心肌梗死模型+积雪草苷组的左心室重量/体重低于心肌梗死模型组(P0.05);免疫组织化学染色结果显示:与心肌梗死模型组比,心肌梗死模型+积雪草苷组非梗死区心肌TGF-β1、ColⅠ、ColⅢ的表达明显降低(P0.05)。心肌梗死大鼠非梗死区心肌梗死组织ColⅠ、ColⅢ表达与心肌组织TGF-β1的表达正相关。结论积雪草苷可减少心肌梗死大鼠非梗死区TGF-β1的表达,从而减弱非梗死区心肌组织ColⅠ、ColⅢ异常合成与沉积,减轻心肌梗死后左室心肌纤维化程度,延缓左室重构的发展。  相似文献   

9.
目的建立体外血管发生的三维立体模型,观察血管内皮生长因子(vascular endothelial growth factor,VEGF)对心肌梗死区血管新生的影响。方法将36只SD大鼠随机为3组,其中实验组、模型组两组结扎冠状动脉左前降支,构建急性心肌梗死动物模型;空白对照组只穿线,不结扎前降支血管。建模成功后,实验组于局部梗死心肌内注射0.5 ng/mL VEGF 50μL,模型组注射等量0.9%氯化钠溶液。取前降支近端梗死心肌组织移植在三维立体培养模型中,每天观察新生血管,培养2周内,记录心肌梗死区新生血管形态及密度,2周后免疫组织化学染色验证梗死心肌周围新生血管。结果 (1)空白对照组,模型组及实验组缺血心肌区域均可见新生血管生成,免疫组织化学显示新生血管碱性成纤维细胞生长因子及平滑肌肌动蛋白染色阳性;(2)实验组新生微血管密度多于模型组及空白对照组,差异有统计学意义(P0.05)。结论 VEGF在体外血管三维立体模型中能增加心脏组织块血管新生,从而促进冠状动脉侧支建立,提高冠状动脉灌注,有希望成为心肌梗死治疗的新手段。  相似文献   

10.
目的 探讨冠脉结扎法制作大鼠急性心肌梗死模型。 方法 40只Sprauge-Dawley大鼠随机分为冠脉结扎组和假手术组,大鼠经麻醉后,气管插管连接小动物呼吸机,打开左侧胸腔,暴露心脏,结扎左冠状动脉前降支,假手术组只用线穿过左前降支而不结 扎,其余步骤同冠脉结扎组。手术前后均行心电图检查,4周后行血流动力学检测,取出心脏,观察其外形变化,行HE染色后于显微镜下观察其病理变化。 结果 冠脉结扎组制作心梗模型成功率为100%,术后存活率为65%,假手术组术后存活率为80%。冠脉结扎组术后4周取出的心脏,左心室较假手术组扩大,缺血区室壁变薄。 结论 冠脉结扎法制作大鼠心肌梗死模型,效果稳定,成功率高,制作方便,经济易推广。  相似文献   

11.
Akpan SS 《Tropical doctor》2007,37(3):192-193
The popularity of insecticide-treated bednets (ITNs) was assessed among 612 residents of Calabar Municipality between June and September 2004. A questionnaire was administered to the respondents, majority of whom (88.9% [544:612]) claimed that they were aware of the use of ITNs for preventing mosquito bites. Only 13.2% of the respondents (72:544) owned ITNs at the time of filling the questionnaire.  相似文献   

12.
Abstract Objective. Delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) of gastric neoplasms. We aimed to clarify risk factors for delayed bleeding from ESD. Material and methods. This study included 447 patients in whom 544 gastric neoplasms were resected by ESD between April 2006 and March 2011 in Yamaguchi University Hospital. We analyzed risk factors for delayed bleeding from ESD in relation to various clinical and pathological factors. Results. En bloc resection rate was 95.4% (519/544), and curative resection rate was 87.8% (477/544). Delayed bleeding occurred in 7.0% (38/544) and perforation occurred in 1.8% (10/544) of patients. Univariate analysis revealed platelet count (Plt) <15 × 10(4)/μl (p = 0.013), prothrombin time (PT) <70% (p = 0.044), resected size ≥50 mm (p = 0.038), and positive/indeterminate lateral margin (p = 0.012) to be risk factors for delayed bleeding. Multivariate analysis showed that Plt <15 × 10(4)/μl (odds ratio [OR], 2.62; 95% confidence interval [CI]: 1.17-5.53, p = 0.020) and positive/indeterminate lateral margin (OR, 5.45; 95% CI: 1.39-17.95, p = 0.018) were independent risk factors for delayed bleeding. Conclusions. Low Plt, low PT, large resected size, and positive/indeterminate lateral margin were significant risk factors for delayed bleeding from ESD. Patients with these risk factors must be carefully observed for signs of delayed bleeding.  相似文献   

13.
Antibody-targeted chemotherapy with gemtuzumab ozogamicin (CMA-676, a CD33-targeted immunoconjugate of N-acetyl-gamma-calicheamicin dimethyl hydrazide [CalichDMH], a potent DNA-binding cytotoxic antitumor antibiotic) is a clinically validated therapeutic option for patients with acute myeloid leukemia (AML). Here, we describe the preclinical profile of another immunoconjugate of CalichDMH, CMC-544, targeted to CD22 expressed by B-lymphoid malignancies. CMC-544 comprises a humanized IgG4 anti-CD22 monoclonal antibody (mAb), G5/44, covalently linked to CalichDMH via an acid-labile 4-(4'-acetylphenoxy) butanoic acid (AcBut) linker. Both CMC-544 and unconjugated G5/44 bound human CD22 with subnanomolar affinity. CMC-544, but not unconjugated G5/44, exerted potent cytotoxicity against CD22+ B-cell lymphoma (BCL) cell lines (inhibitory concentration of 50%: 6-600 pM CalichDMH). CMC-544 caused a potent inhibition of growth of small but established BCL xenografts leading to cures (therapeutic index > 10). CMC-544 prevented the establishment of BCL xenografts and also caused regression of large BCLs (> 1.5 g tumor mass). In contrast, unconjugated CalichDMH, unconjugated G5/44, and an isotype-matched control conjugate, CMA-676, were ineffective against these BCL xenografts. Thus, CD22-targeted delivery of CalichDMH is a potent and effective preclinical therapeutic strategy for BCLs. The strong antitumor profile of CMC-544 supports its clinical evaluation as a treatment option for B-lymphoid malignancies.  相似文献   

14.
Central illustration. Potential impact of colchicine on the pathways involved in atherosclerosis. IL: interleukin; MMP: matrix metalloproteinase; SMC: smooth muscle cells. Adapted from [42].
  相似文献   

15.
目的:比较术前联合放化疗联合手术与单纯手术对可切除食管癌患者的影响.方法:使用计算机及手工检索两种方法在Pubmed和Embase中搜索相关随机对照实验,以确保无文献遗漏.结果:共纳入包含1544名患者的12篇文献.术前联合放化疗较单纯手术明显提高了患者的1年、3年和5年生存率,其OR(95%CI,P值)分别为1.28(1.01-1.64,P=0.05);1.84(1.29-2.63,P=0.00);1.53(1.17-2.00,P=0.00).术前放化疗增加了术后死亡率,但并不增加术后的并发症发生率,其OR(95%CI;P值)分别为1.71(1.06-2.76,P=0.03)和1.15(0.89-1.49,P=0.28).术前放化疗降低了肿瘤局部复发率,但对远处转移无影响,其对应的OR(95%CI,P值)分别为0.64(0.41-0.99,P=0.04)和0.94(0.58-1.31,P=0.73).结论:术前放化疗联合手术可显著改善食管癌患者的生存率,值得临床应用推广.  相似文献   

16.
Abstract

Objective. Delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) of gastric neoplasms. We aimed to clarify risk factors for delayed bleeding from ESD. Material and methods. This study included 447 patients in whom 544 gastric neoplasms were resected by ESD between April 2006 and March 2011 in Yamaguchi University Hospital. We analyzed risk factors for delayed bleeding from ESD in relation to various clinical and pathological factors. Results. En bloc resection rate was 95.4% (519/544), and curative resection rate was 87.8% (477/544). Delayed bleeding occurred in 7.0% (38/544) and perforation occurred in 1.8% (10/544) of patients. Univariate analysis revealed platelet count (Plt) <15 × 104/μl (p = 0.013), prothrombin time (PT) <70% (p = 0.044), resected size ≥50 mm (p = 0.038), and positive/indeterminate lateral margin (p = 0.012) to be risk factors for delayed bleeding. Multivariate analysis showed that Plt <15 × 104/μl (odds ratio [OR], 2.62; 95% confidence interval [CI]: 1.17–5.53, p = 0.020) and positive/indeterminate lateral margin (OR, 5.45; 95% CI: 1.39–17.95, p = 0.018) were independent risk factors for delayed bleeding. Conclusions. Low Plt, low PT, large resected size, and positive/indeterminate lateral margin were significant risk factors for delayed bleeding from ESD. Patients with these risk factors must be carefully observed for signs of delayed bleeding.  相似文献   

17.
The effect of CMC-544, a calicheamicin-conjugated anti-CD22 monoclonal antibody, was analysed in relation to CD22 and P-glycoprotein (P-gp) in B-cell chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) in vitro . The cell lines used were CD22-positive parental Daudi and Raji, and their P-gp positive sublines, Daudi/MDR and Raji/MDR. Cells obtained from 19 patients with B-cell CLL or NHL were also used. The effect of CMC-544 was analysed by viable cell count, morphology, annexin-V staining, and cell cycle distribution. A dose-dependent, selective cytotoxic effect of CMC-544 was observed in cell lines that expressed CD22. CMC-544 was not effective on Daudi/MDR and Raji/MDR cells compared with their parental cells. The MDR modifiers, PSC833 and MS209, restored the cytotoxic effect of CMC-544 in P-gp-expressing sublines. In clinical samples, the cytotoxic effect of CMC-544 was inversely related to the amount of P-gp ( P  = 0·003), and to intracellular rhodamine-123 accumulation ( P  < 0·001). On the other hand, the effect positively correlated with the amount of CD22 ( P  = 0·010). The effect of CMC-544 depends on the levels of CD22 and P-gp. Our findings will help to predict the clinical effectiveness of this drug on these B-cell malignancies, suggesting a beneficial effect with combined use of CMC-544 and MDR modifiers.  相似文献   

18.
19.
OBJECTIVE: The cellular effects of growth hormone (GH) are mediated by the interaction between GH and the GH receptor (GHR). We investigated the association between polymorphisms in GHR and changes in height standard deviation scores (SDS), and lipid metabolism during GH treatment for GH-deficient children. DESIGN: A 1-year study on growth rate and lipid metabolism under GH treatment. PATIENTS: Eighty-three children (61 boys and 22 girls) with GH deficiency were treated with GH for 1 year after diagnosis. INTERVENTION: The patients were treated with recombinant human GH (0.19 mg/kg/week) for at least 1 year after diagnosis. The growth rates and biochemical parameters for lipid metabolism were measured both before and during treatment. Four single nucleotide polymorphisms (SNPs) in the GHR gene, Cys440Phe, Pro495Thr, Leu544Ile and Pro579Thr, and exon 3 deletion polymorphisms were genotyped by direct sequencing and multiplex PCR. RESULTS: We found no significant association between GHR polymorphisms and changes in height SDS during GH treatment. The total cholesterol levels of the GH-deficient boys with Ile/Ile at codon 544 showed significantly higher cholesterol levels before GH treatment and then maintained high levels during the GH treatment, compared to those with other genotypes. No other polymorphisms seemed to have any apparent effects on lipid metabolism. CONCLUSION: The Leu544Ile polymorphism of the GHR gene is associated with cholesterol levels in boys with GH deficiency.  相似文献   

20.
Aim: This study explored recent improvements in the management of hepatocellular carcinoma (HCC) diagnosed during surveillance. Methods: The subjects were 1074 patients with HCC, subdivided into three groups. Group A comprised 211 patients for whom HCC was detected during periodic follow‐up examinations at Kurume University School of Medicine, Group B comprised 544 patients diagnosed with HCC during periodic follow‐up examinations at other institutions, and, Group C comprised 319 patients with HCC detected incidentally or because of symptoms. Results: In 1995–2000 and 2001–2006, 91% and 91% of group A, 68% and 70% of group B, and 27% and 26% of group C patients with HCC, respectively, met the Milan criteria. For groups A and B, the proportions of patients with Child–Pugh class A and use of promising treatment increased in the later periods compared to those diagnosed during the earlier periods (group A, Child–Pugh class A, 72% vs 58% [P = 0.040], receiving treatment, 90% vs 70% [P < 0.0001]; group B, Child–Pugh class A, 71% vs 62% [P = 0.031]; receiving treatment, 72% vs 52% [P < 0.0001], respectively). The cumulative survival rates of the 405 patients with HCC detected in the latter 6 years tended to be better than those for patients diagnosed in the former 6 years (350 patients) (4 years, 58% vs 50% [P = 0.0349]). Conclusion: The use of promising treatment and prognosis have improved in the last 6 years for patients with HCC diagnosed through surveillance relative to those identified in 1995–2000.  相似文献   

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