大鼠实验性糖尿病对异丙肾上腺素所致心肌坏死的影响

异丙肾上腺素(ISP)是一种强有力的心脏毒性物质。给动物注射一定剂量可引起明显心肌坏死。糖尿病时可发生心肌病改变,为探讨糖尿病心肌对致损伤因素的反应特点,本实验研究了糖尿病状态对ISP所致心肌坏死的影响。由于甲状腺功能状态可影响儿茶酚胺的反应性,故同时也探讨了糖尿病大鼠血清甲状腺激素水平对这种心肌坏死的影响。     

白细胞介素8对异丙肾上腺素所致大鼠心肌细胞坏死的影响

近年发现白细胞介素8(IL-8)具有抑制中性粒细胞与血管内皮细胞粘附的作用,本工作用重组IL-8治疗异丙肾上腺素(ISO)所致大鼠心肌坏死。与单纯ISO组比较,重组IL-8治疗明显减轻ISO引起的心肌坏死,使心肌丙二醛含量减少、降低心肌髓过氧化物酶活性,使血浆内皮素放免活性明显降低。实验结果提示,IL-8可以通过抑制白细胞粘附和浸润,抑制内皮素释放,防治缺血心肌坏死。     

异丙肾上腺素对大鼠血浆内皮素-1的影响

血管内皮细胞(EC)广泛分布于全身血管腔的表面,在维持机体正常生理及新陈代谢功能等方面均有重要作用.血管内皮细胞何以合成和分泌多种生物活性物质参与心肌的损伤过程.但在异丙肾上腺素(ISO)心肌损伤模型中,血管内皮细胞功能的变化却少有报道.本实验通过测量大鼠血浆中内皮素-1(ET-1)及前列环素代谢产物6-酮前列腺素F.(6-Keto-PGF1α)含量探讨ISO对血管内皮细胞功能的影响.     

曲美他嗪对异丙肾上腺素所致大鼠心肌肥厚的影响

目的探讨曲美他嗪（TMZ）对异丙肾上腺素（ISO）致大鼠心肌肥厚的影响及可能的作用机制。方法30只Sprague-Ddwley（SD）大鼠,随机分为3组。正常对照组、ISO组、TMZ组,每组10只。通过大剂量注射ISO制成心肌肥厚模型,以TMZ干预,观察心肌组织病理学变化和心肌细胞超微结构改变,计算心脏质量/体质量（HW/BW）,测定心肌三磷酸腺苷（ATP）、丙二醛（MDA）、超氧化物歧化酶（SOD）和血清乳酸脱氢酶（LDH）、肌酸激酶（CK）含量。结果TMZ组与ISO组比较,HW/BW、LDH、CK、SOD和ATP有显著差异（P<0.05）,而与正常对照组比较无显著差异。TMZ组心肌组织病理损伤程度及细胞超微结构改变程度,较ISO组明显减轻,而接近正常对照组。结论TMZ可拮抗ISO所致的大鼠心肌肥厚,其机制可能与改善心肌能量代谢、提高组织对缺氧的耐受力、消除氧自由基等有关。     

虾青素对异丙肾上腺素诱导的大鼠心肌纤维化的影响

目的 探讨虾青素对异丙肾上腺素（ISO）诱导的大鼠心肌纤维化的影响。方法 SD大鼠腹腔注射异丙肾上腺素（5mg/kg/d），连续注射14d，建立心肌纤维化模型，从造模第二天开始给予虾青素（5mg/kg/d和10mg/kg/d）灌胃，连续21天。实验结束后超声心动图检测大鼠心脏功能，计算心脏指数，Masson染色观察心肌纤维化水平，Western blotting 方法检测心肌胶原Ⅲ、转化生长因子-β1（TGF-β1）蛋白的表达。结果 与正常对照组比较，模型组左心室射血分数（EF）和左心室短轴缩短分数（FS）明显降低（P<0.05）,心脏指数增加，心肌纤维化明显，胶原蛋白Ⅲ及TGF-β1表达水平增加（P<0.05）；与模型组比较，低剂量虾青素组和高剂量虾青素组EF和FS明显升高（P<0.05），心脏指数减低（P<0.05），心肌纤维化程度减低，心肌胶原蛋白Ⅲ、TGF-β1表达水平明显降低（P<0.05）。 结论 虾青素能够降低异丙肾上腺素诱导的心肌纤维化水平，改善心功能。     

Calpain 1在黄芪甲苷抑制异丙肾上腺素诱导的大鼠心肌凋亡中的作用

目的探讨Calpain 1在黄芪甲苷抑制异丙肾上腺素诱导的大鼠心肌凋亡中的作用。方法 SD大鼠48只,随机分为6组,每组8只:正常对照组、异丙肾上腺素组、异丙肾上腺素+普萘洛尔40 mg/(kg·d)组、异丙肾上腺素+黄芪甲苷20 mg/(kg·d)组、异丙肾上腺素+黄芪甲苷40 mg/(kg·d)组、异丙肾上腺素+黄芪甲苷80mg/(kg·d)组。给药组连续灌胃2周,并于灌胃1天后腹腔注射异丙肾上腺素10 mg/(kg·d)2周。2周后,采用TUNEL检测心肌凋亡,电镜观察心肌线粒体病变,Western blot检测心肌线粒体Calpain 1、凋亡诱导因子(AIF)的蛋白表达和心肌组织多聚ADP核糖聚合酶1(PARP1)的蛋白表达。结果与正常对照组相比,异丙肾上腺素组凋亡率明显增加;心肌线粒体肿胀、膜融合消失、嵴断裂;心肌线粒体中Calpain 1表达增加,AIF表达减少;心肌组织中PARP1表达增加。与异丙肾上腺素组相比,异丙肾上腺素+黄芪甲苷40 mg/(kg·d)组、异丙肾上腺素+80mg/(kg·d)组表现为心肌凋亡率减少;心肌线粒体结构相对完整;心肌线粒体Calpain 1表达减少,AIF表达增加;心肌组织PARP1表达减少,且呈一定的剂量依赖性。结论黄芪甲苷对异丙肾上腺素诱导的心肌凋亡有一定的保护作用,其机制可能与抑制线粒体Calpain 1表达,从而减少线粒体AIF释放至胞浆并转位至核有关。     

比索洛尔对异丙肾上腺素引起的大鼠心肌纤维化的干预研究

目的探讨异丙肾上腺素引起的心肌纤维化和比索洛尔对其抑制作用。方法52只Wistar(WS)大鼠随机分为3组:(1)异丙肾上腺素组20只,腹部皮下注射异丙肾上腺1mg/Kg/d;(2)比索洛尔组20只,预先用比索洛尔2mg/Kg/d灌胃,3天后加用异丙肾上腺素1mg/Kg/d皮下注射;(3)对照组12只,腹部皮下注射生理盐水1ml/d。3组均连续腹部皮下注射10天。第15天杀死全部大鼠,分别计算出每只大鼠的心室/体重指数;心室胶原蛋白浓度。结果与对照组相比,异丙肾上腺素组心室/体重指数为6.28±1.10mg/g,明显增加(P<0.01);心室组织胶原蛋白浓度为8.717±0.795ng/mg,明显升高(P<0.05)。与异丙肾上腺素组相比,比索洛尔组心室/体重指数为5.53±0.87mg/g,心室组织胶原蛋白浓度为7.897±0.107ng/mg,均明显下降(P<0.05)。结论大剂量异丙肾上腺素可引起大鼠心肌纤维化,比索洛尔可以有效抑制这一过程。     

左旋卡尼汀对异丙肾上腺素致心肌损害的影响

目的:观察左旋卡尼汀对异丙肾上腺素致心肌损害的保护作用并探讨其机制。方法:采用大鼠皮下注射异丙肾上腺素造成心肌损害模型。心肌切片,HE染色,光镜下观察心肌损害程度;分离心肌线粒体,测定膜脂流动性（LFU）。结果:注射左旋卡尼汀可减轻心肌损害程度;改善线粒体的损伤,改善LFU。结论:左旋卡尼汀能减轻异丙肾对心肌的损害,对线粒体膜脂流动性损伤具有明显的保护作用。     

异丙肾上腺素增加“缺血”浦肯野纤维起搏离子流的实验

采用双微电极电压钳制术测定正常及模拟“缺血”时，异丙肾上腺素对绵羊心脏浦肯野纤维起搏离于流的影响。结果：异丙肾上腺素１×１０－６ｍｏｌ／Ｌ显著增加浦肯野纤维起搏离子流幅值；模拟“缺血”使起搏离子流幅值降低，在此基础上，异丙肾上腺素仍增加起搏离子流，但未能恢复到“缺血…前水平。     

蜂胶总黄酮对异丙肾上腺素致病理性心肌肥厚小鼠心功能的影响

目的探讨蜂胶总黄酮(TFP)对异丙肾上腺素(ISO)诱导的病理性心肌肥厚(PCH)小鼠心功能的影响。方法 8周龄雄性小鼠20只,适应性饲养1 w,随机分为对照组、ISO组、TFP组及ISO+TFP组。预先口服TFP(25 mg·kg-1·d-1)7 d之后持续给予ISO(25 mg·kg-1·d-1)7 d制备小鼠PCH模型。试验结束后24 h进行超声心动图检测,计算心脏重量/体重(HW/BW)比值,检测心房钠尿肽(ANP)的mRNA和蛋白表达水平。结果与对照组比较,ISO组小鼠收缩期左室内径(LVIDs)、舒张期左室内径(LVIDd)及左室收缩末期容积(LVVs)均明显升高,而射血分数(EF)、缩短分数(FS)明显降低,HW/BW及ANP蛋白、mRNA水平亦明显升高(P0.05);与ISO组比较,TFP+ISO组LVIDs、LVIDd及LVVs均明显降低,而EF、FS明显升高(P0.05),HW/BW及ANP蛋白、mRNA水平亦明显降低(P0.05)。结论 TFP可对抗ISO诱导的小鼠PCH,并对心功能损伤具有保护作用。     

Modulation of ICAM-1 expression in ECV304 cells by macrophage-released cytokines

Transendothelial leukocyte trafficking during inflammation requires the expression of adhesion molecules such as human intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is constitutively expressed on the surface of endothelial cells and its levels increase in response to a variety of inflammatory mediators, including cytokines. Monocyte/macrophage cells play a crucial role in this context because, upon stimulation, they release proinflammatory cytokines which are responsible for the upregulation of adhesion molecules in endothelial cells. In the present study we investigated whether the modulation of macrophage activation and cytokine release is able to modulate ICAM-1 expression in endothelial cells. Dexamethasone was selectively delivered to macrophages by means of a red blood cell-mediated delivery system. Subsequent stimulation of macrophages by lipopolysaccharide (LPS) was found to inhibit NF-kB activation and tumor necrosis factor-alpha (TNF-alpha) release [R. Crinelli, A. Antonelli, M. Bianchi, L. Gentilini, S. Scaramucci, and M. Magnani (2000) Blood Cells Mol. Dis. 26, 211-222]. Incubation with conditioned medium derived from LPS-stimulated macrophages receiving dexamethasone resulted in a 45% inhibition of ICAM-1 mRNA expression in ECV304 cells. In the same experimental system this reduced ICAM-1 expression was paralleled by a reduced NF-kB DNA binding activity and a twofold higher level of IkB(alpha) in the cytosol of endothelial cells. Activation of ICAM-1 expression in ECV304 cells by macrophage-conditioned medium is not due to IFN-gamma stimulation since STAT-1 DNA binding remained unchanged. Furthermore, treatment of the macrophage-conditioned medium with a TNF-alpha-inactivating antibody resulted in the complete abrogation of induced ICAM-1 expression. These results suggest that TNF-alpha is the main cytokine released by LPS-stimulated macrophages able to promote ICAM-1 gene expression in endothelial cells. Modulation of the NF-kB activation pathway in macrophages by targeted delivery of dexamethasone could potentially be used as a therapeutic strategy with which to inhibit the expression of ICAM-1 in endothelial cells.     

冠心病患者细胞间粘附分子-1变化的研究

目的:观察心绞痛、急性心肌梗死时血清细胞问粘附分子-1(ICAM-1)水平的变化,以探讨其与冠心病的关系及意义。方法:选择健康体检者(正常对照组)30例、稳定性心绞痛(SAP)患者(SAP组)20例、不稳定性心绞痛(UAP)患者(UAP组)25例和急性心肌梗死(AMI)患者(AMI组)30例,采用酶联免疫吸附分析法(ELISA法)检测血清中ICAM-1浓度的变化。结果:(1)SAP组、UAP组、AMI组与正常对照组比较;血清中ICAM-1水平显著升高(P<0.01);(2)与SAP组比较,UAP组、AMI组血清ICAM-1水平显著升高(P均<0.01);(3)与UAP组比较,AMI组血清ICAM-1水平显著升高(P<0.05)。结论:血清中ICAM-1水平的高低与冠心病的严重程度有关,具有判断病情和预后的价值。     

芪参降脂饮对高胆固醇血症大鼠主动脉ICAM-1表达量的影响

目的观察芪参降脂饮对高胆固醇血症大鼠主动脉ICAM-1的表达的影响.方法 24只SD大鼠随机分为3组:对照组8只,喂普通饲料;模型组8只,喂高脂饲料;中药组8只,喂高脂饲料,同时给予芪参降脂饮灌胃.6周后急性处死.取血测血脂;用免疫组织化学检测主动脉血管壁细胞间黏附分子-1(ICAM-1)蛋白表达水平.结果中药组大鼠血清胆固醇水平明显低于模型组(P<0.05),模型组大鼠主动脉血管壁ICAM-1蛋白表达量明显高于中药组(P<0.01).结论芪参降脂饮能够降低实验性高胆固醇血症大鼠血脂,抑制ICAM-1在主动脉血管壁的表达.     

慢性乙型肝炎肝组织ICAM-1 mRNA和ICAM-1表达及意义

目的探讨肝组织间粘附分子-1(ICAM-1)表达在慢性乙型肝炎(CHB)发病机理中的作用。方法用原位杂交和免疫组织化学技术检测11例正常人和50例慢性HBV感染者肝内ICAM-1 mRNA和ICAM-1表达情况。结果正常人和慢性无症状HBsAg携带者肝细胞无ICAM-1mRNA和ICAM-1表达,CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达增强,阳性肝细胞多分布在汇管区周围和腺泡内炎症坏死区域;重度CHB患者肝细胞ICAM-1 mRNA和ICAM-1表达显著强于中、轻度CHB患者(P<0.05);肝细胞ICAM-1表达强度与肝组织炎症活动度呈显著正相关,p<0.01;肝细胞ICAM-1表达强的患者肝功能显著差于ICAM-1表达弱者,P<0.05。结论肝细胞ICAM-1表达在慢性乙型肝炎肝细胞坏死中起重要作用,肝细胞ICAM-1表达水平能较好反映其肝损害程度和肝功能状况。     

Differential expression of two ICAM-1 epitopes and LFA-1 chains in B-cell non-Hodgkin's lymphomas

Abstract: B-cell non-Hodgkin's lymphomas (B-NHL) and B-cell areas of reactive lymphadenopathies were investigated immunohistochemically for expression of two distinct ICAM-1 epitopes, Me14/D12 and P3-58, and the LFA-1 α and β chains. Partial or total loss of expression of one or both epitope(s) and/or chain(s) was evident in all B-NHL in function of increasing Working Formulation (WF) malignancy grade, with most defects in the high-grade tumors, namely the lowest detectability of the ICAM-1 Me14/D12 and LFA-1 α chain, the lowest co-expression of ICAM-1 epitopes and LFA-1 chains, and the most frequent simultaneous loss. The ICAM-1 and LFA-1 profiles overlapped within the low- and intermediate-grades, whereas striking differences between the high-grade subtypes were detected. Specifically, Burkitt's and lymphoblastic tumors always lost both epitopes and both chains. Large cell, immunoblastic tumors occasionally did so, and also showed either uncoordinated expression or co-expression of these constituents. It is suggested that expression defects of this type may help differentiate malignant from benign lymphoproliferations, and also be involved in the progression of B-NHL, since most are observed in high-grade tumors, whose ICAM-1 and LFA-1 profiles indicate that their subtypes are the expression of distinct normal B-cell differentiation stages.     

乳腺癌组织及淋巴结中细胞间粘附分子表达与其浸润转移关系探讨

目的探讨细胞间粘附分子（ICAM-1）表达与乳腺癌的关系。方法应用免疫组织化学ABC法检测乳腺癌及其腋下淋巴结中ICAM－1的表达．结果乳腺癌组织中ICAM-1的表达明显高于乳腺腺癌，转移癌与未转移癌组之间相比差异非常显著，且与病理分级呈负相关趋势，腋下转移淋巴结与非转移淋巴结中ICAM-1表达阳性率无差别，但阳性度方面明显不同。结论乳腺癌组织中ICAM－1检测可以作为判定患者机体免疫功能状态及预后的客观指标．     

细胞间黏附分子-1和P-选择素的表达与非小细胞肺癌关系的研究

目的探讨细胞间黏附分子-1(ICAM-1)和P-选择素在肺癌转移机制中的作用。方法采用免疫组化SP法对52例原发性肺癌组织的ICAM-1及P-选择素的表达进行检测。结果(1)肺癌的ICAM-1和P-选择素阳性表达明显高于癌旁组织;(2)ICAM-1及P-选择素在腺癌组织中的阳性表达率显著高于鳞癌,两者在Ⅲ Ⅳ期患者的阳性表达明显高于Ⅰ Ⅱ期;(3)肺癌中有淋巴结转移的ICAM-1的阳性表达率显著高于无淋巴结转移,而P-选择素的表达与淋巴结转移无明显相关性。结论ICAM-1和P-选择素可能与肺癌的浸润转移有关。     

P-selectin、IVAM-1和ICAM-1在大鼠重症急性胰腺炎并发急性心肌损害中的作用机制

目的:研究大鼠重症急性胰腺炎(SAP)并发急性心肌损害(AMD)时心肌组织黏附分子(P-selectin、VCAM-1、ICAM-1)基因表达的变化以及丹红注射液对表达的影响.方法:90只S-D大鼠随机分为对照组(A组,n=30)、SAP模型组(B组,n=30)和治疗组(C组,n=30),采用腹腔注射L-Arg的制作S...     

The Effect of Dehydroepiandrosterone on the Expression of AT1 receptor and TNF-induced ICAM-1 in Vascular Smooth Muscle Cells

Objectives To further investigate the molecular mechanism of vasoprotective role of dehydroepiandrosterone (DHEA), we examined DHEA on AT1 receptor and ICAM-1 gene expression in vascular smooth muscle cells (VSMCs). Methods RT-PCR and Western Blot was used to determine the change of the expressions of mRNA and protein of AT1 and ICAM-1 when given various concentration dehydroepiandrosterone. Results 1.AT1 was abundant under the basal condition. The expression of AT1 mRNA and protein decreased after stimulated by DHEA (at 10^-10mol/L, 10^-8mol/L, 10^-6mol/L), and the effects of DHEA on AT1 protein was dose-dependent. ER inhibitor Tamoxifen and AR inhibitor Flutamide enhanced AT1 protein expression, but did not influence the mRNA expression. 2. The exp-ression of ICAM-1 gene was low under the basal condition.It increased when induced by TNF-α, but decreased when induced by DHEA (at 10^-10mol/L, 10^-8moL/L, 10^-6mol/L) ,and the effects of DHEA on ICAM-1 gene expression were dose-dependent. Conclusions These findings suggest that DHEA modulates AT1 and inflammatory factor induced ICAM-1 gene expression in VSMC, butfurther studies are necessary in the mecha-nism of DHEA action.