Apelin-APJ系统在1型糖尿病肾病大鼠发病中的作用

目的：探讨血管紧张素1型受体相关蛋白（putative receptor protein related to AT1,apelin-APJ）系统在糖尿病肾病发生中的作用及机制。方法：20只大鼠应用链脲佐菌素（STZ60mg/kg体重）构建1型糖尿病大鼠模型后随机分为三组,正常对照组（N）、糖尿病组（DN）、apelin干预组（T）。于应用apelin-13前、后4周,8周,12周测定三组大鼠24h尿微量白蛋白量、尿白蛋白/血肌酐指数;应用apelin-13前和12周时采血分别测定血肌酐（Scr）;应用ELISA法检测血清apelin-13水平;应用Western blot和免疫组化方法检测大鼠肾组织APJ受体和AngⅡ相关的1型受体（AT1R）的蛋白表达量。结果：与N组比较,DN组大鼠尿微量白蛋白、尿白蛋白/血肌酐指数显著升高（P〈0.01）,肾组织APJ受体的蛋白表达量显著下降（P〈0.01）,AT1R的表达量显著升高。与DN组比较,T组大鼠尿微量白蛋白、白蛋白/肌酐指数显著下降（P〈0.05）,肾组织APJ受体的蛋白表达量显著上升（P〈0.01）,AT1R的表达量显著下降。N组与T组大鼠尿微量白蛋白、白蛋白/肌酐指数、肾组织APJ受体和AT1R的蛋白表达量之间差异无统计学意义。结论：Apelin-APJ系统可能参与了糖尿病肾病的发病过程,其可能通过拮抗AngⅡ-AT1R的作用而对糖尿病大鼠肾脏起保护作用。     

反义血管紧张素Ⅱ受体Ⅰ_B基因转移对大鼠颈动脉损伤后新生内膜的影响

目的　探讨腺病毒载体介导的大鼠反义血管紧张素Ⅱ受体ⅠB(AT1B)RNA转移对大鼠颈动脉损伤后新生内膜的影响。方法　利用重组腺病毒载体将大鼠反义AT1B RNA转移至大鼠颈动脉球囊损伤模型中 ,2 1天后观察其对新生内膜形成的影响。结果　用腺病毒载体转导大鼠反义AT1BRNA至大鼠球囊损伤的颈动脉 ,与对照组相比 ,2 1天后损伤血管新生内膜 /中层面积比降低了 4 7%(P <0 0 0 1)。结论　反义AT1BRNA对血管成形术后再狭窄可能有一定的预防作用。     

Haemodynamic, neurohumoral and exercise effects of losartan vs. captopril in chronic heart failure: results of an ELITE trial substudy. Evaluation of Losartan in the Elderly

BACKGROUND: The AT1 receptor antagonists differ from the angiotensin converting enzyme inhibitors by achieving a more complete blockade of angiotensin II's actions and by not affecting bradykinin metabolism. There is little information on whether this causes clinically significant differences in haemodynamics, neurohormones and exercise tolerance in heart failure. AIMS: To compare the effects of losartan and captopril upon central and regional haemodynamics, neurohormones and exercise capacity in heart failure. METHODS: In a double-blind, randomised trial 18 patients aged > or =65 years with symptomatic heart failure were allocated to treatment with losartan (10 patients) or captopril (eight patients). Patients underwent assessment at baseline, after the first dose, at 12 weeks and at 24 weeks. RESULTS: Systolic blood pressure fell by - 10.7% 1 h after captopril 6.25 mg (P = 0.007) and by - 4.8% 3 h after losartan 12.5 mg (P = 0.02). The blood pressure reduction was sustained with losartan at 12 and 24 weeks. Systemic vascular resistance fell acutely after captopril (-16.4%, P = 0.01). Captopril caused an acute and sustained rise in superior mesenteric artery blood flow (+ 22.9%, P = 0.04), and a slower rise in renal artery blood flow (+31.7%, P = 0.01). Losartan had no acute effects on regional haemodynamics but had increased superior mesenteric artery blood flow by 38.1% at 12 weeks (P = 0.02). There were no substantial differences between losartan and captopril, and no changes occurred in neurohormones or exercise capacity. CONCLUSION: No substantial differences were observed between losartan and captopril on central or regional haemodynamics, neurohormones or exercise capacity in elderly patients with stable symptomatic heart failure.     

运用BiFC技术检测LOX-1与AT1受体的相互作用

目的运用双分子荧光互补(bimolecular fluorescence complementation,BiFC)技术探讨氧化低密度脂蛋白(ox-LDL)介导血凝素样氧化低密度脂蛋白受体-1(LOX-1)和血管紧张素Ⅱ1型受体(AT1)之间的相互作用,推测其可能是参加动脉粥样硬化等心血管疾病过程的重要机制之一。方法将LOX-1与AT1受体质粒共转染COS7细胞,给予ox-LDL(50ug/ml)刺激后,检测细胞中p-ERK表达水平。根据BiFC载体和AT1、LOX-1基因序列设计引物,将AT1、LOX-1基因克隆到BiFC特异性的荧光载体上,得到重组BiFC质粒:phmKGN-MN-AT1,phmKGC-MN-AT和phmKGC-MC-LOX-1,phmKGN-MC-LOX-1,配对共转染HEK293细胞,用ox-LDL(50ug/ml)刺激,研究AT1受体和LOX-1的相互作用;构建G蛋白偶联受体家族中另一蛋白肾上腺素受体β2(β2-adrenergi creceptor,β2AR)的BiFC重组质粒:phmKGN-MN-β2AR和phmKGC-MN-β2AR,分别与LOX-1对应的BiFC质粒转染HEK...     

Odorants could elicit repair processes in melanized neuronal and skin cells

The expression of ectopic olfactory receptors(ORs) in melanized cells, such as the human brain nigrostriatal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin melanogenesis, whereas OR expression in the dopaminergic neurons, characterized by accumulation of pigment neuromelanin, is downregulated in Parkinson's disease. Furthermore, the correlation between the pigmentation process and the dopamine pathway through α-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pigmentation disorders. Based on this evidence, a possible way of turning odorants into drugs, acting on three specific olfactory receptors, OR51E2, OR2AT4 and VN1R1, is thus introduced. Various odorous molecules are shown to interact with these ORs and their therapeutic potential against melanogenic and neurodegenerative dysfunctions, including melanoma and Parkinson's disease, is suggested. Finally, a direct functional link between olfactory and endocrine systems in human brain through VN1R1 is proposed, helping to counteract female susceptibility to Parkinson's disease in quiescent life.     

AT1R、ACE基因多态性与东乡族原发性高血压的关系及其对降压药疗效的影响

目的：探讨血管紧张素转换酶（ACE）、血管紧张素Ⅱ（AngⅡ）Ⅰ型受体（ATIR）基因多态性与甘肃东乡族原发性高血压（EH）的关系。对不同基因型患者使用AT1R拮抗剂治疗，观察其疗效。方法：应用聚和酶链反应（PCR）方法检测汉族健康131例、东乡族健康102例、汉族EH198例、东乡族EH115例的AT1RA／C、ACE I／D基因多态性。随机选取60名EH患者，按其基因型分成AA和AC（AA、AC为基因型）两组，使用缬沙坦治疗8周，比较治疗前后血压变化。结果：ACE基因Ⅱ型在汉族EH组明显高于东乡族EH组（P〈0．05），ID基因型在东乡族EH组明显高于汉族EH组（P〈0．01）；AT1R基因AC型汉族EH组明显高于东乡族EH组（P〈0．05）；AA型在东乡族EH组明显高于汉族EH组（P〈0．05）。使用缬沙坦治疗8周，各基因型在治疗后患者血压均下降显著（P〈0．05）。不同基因型之间治疗后比较，降压效果无差异。结论：AT1R基因AA型和ACE基因ID型与东乡族EH有关；ACE基因Ⅱ型和AT1R基因AC型与汉族EH有关，C和D等位基因与汉族和东乡族EH无关。使用缬沙坦对不同基因型患者进行药物治疗，降压疗效相同，说明降压疗效与基因型无关。     

基于AT90S8535单片机的智能止鼾器研究

分析了当前止鼾器的原理及不足，介绍了ATMEL公司生产的AT90S8535单片机主要特点以及在智能止鼾器中的应用方法，给出了AT90S8535单片机的部分控制电路图，最后简要说明了单片机的主程序以及各个中断服务程序。     

血管紧张素Ⅱ受体、p53和Survivin在乳腺癌中的表达及相关性研究

目的：研究AT1受体、AT2受体、凋亡抑制基因p53、Survivin在乳腺癌中的表达情况,并探讨其相关性及临床意义。方法：采用免疫组化方法（SP法）,对102例乳腺癌患者石蜡包埋切片中的AT1受体、AT2受体、Survivin及p53蛋白进行检测,采用χ^2检验对结果进行分析。结果：乳腺癌组织中AT1受体的阳性表达率为48%（49/102）,AT1受体表达与患者年龄、肿瘤大小、ER、PR无相关性,而与腋淋巴结转移呈正相关;乳腺癌组织中AT2受体的阳性表达率为59.8%（61/102）,AT2受体表达与患者年龄、肿瘤大小、ER、PR无相关性,而与腋淋巴结转移成呈负相关;AT1受体表达与p53、Survivin表达呈正相关,AT2受体表达与p53、Survivin表达呈负相关,AT1受体表达与AT2受体表达呈负相关。结论：血管紧张素Ⅱ受体参与乳腺癌肿瘤细胞凋亡。