β1受体阻断药的抗氧化机制

β1受体阻断药除阻滞β受体外,还有许多辅助特性,如内源性交感活性□膜稳定作用和脂溶性。与抗氧化作用有关,β1受体阻断药的抗氧化特性是目前治疗心血管疾病新的机制之一。现就一些β1受体阻断药对机体氧化反应的影响和可能机制作一综述。     

α2受体激动药

介绍α２受体激动药可乐定和右美托咪啶的药理性质，对生理功能的影响以及临床应用。α２受体激动药使吸入麻醉药ＭＡＣ降低，对手术刺激有抑制作用，使循环系统稳定，并有增强和延长镇痛效果，对术后镇痛有良好作用。     

α_2受体激动药

介绍α_2受体激动药可乐定和右美托咪啶的药理性质,对生理功能的影响以及临床应用。α_2受体激动药使吸入麻醉药MAC降低,对手术刺激有抑制作用,使循环系统隐定,并行增强和延长镇痛效果,对术后镇痛有良好作用。     

腹腔镜胃十二肠溃疡穿孔修补辅助H2受体拮抗剂治疗急性胃十二指肠溃疡穿孔

目的:总结腹腔镜下胃十二指肠溃疡穿孔修补术的临床经验。方法:回顾分析采用腹腔镜行胃十二指肠溃疡穿孔修补术的33例临床资料。结果:除1例十二指肠溃疡穿孔时间较长中转手术外,29例十二指肠球部穿孔和3例胃穿孔患者腹腔镜手术均获得成功,无并发症发生;术后辅助H2受体拮抗剂治疗,胃镜复查无复发。结论:腹腔镜修补并H2受体阻断剂口服治疗胃十二指肠溃疡急性穿孔的效果是肯定的,值得临床应用推广。     

GLP-1受体激动剂对2型糖尿病患者骨折风险影响的Meta分析

目的系统评价GLP-1受体激动剂(GLP-1RAs)对2型糖尿病患者骨折风险的影响。方法系统检索Pub Med、Medline、Embase、Cochrane图书馆、Web of science、CNKI及万方数据库。根据纳入排除标准筛选使用GLP-1RAs治疗2型糖尿病的随机对照试验(RCT)。利用Rev Man 5.0及Stata 12.0软件进行分析。结果最终纳入符合标准的RCT36篇,Meta分析结果显示:利拉鲁肽治疗2型糖尿病患者骨折风险低于对照组,差异有统计学意义[OR=0.47,95%CI(0.24,0.91),P=0.024],而与对照组相比,GLP-1 RAs[OR=0.94,95%CI(0.64,1.37),P=0.735]、艾塞那肽[OR=1.81,95%CI(0.83,3.95),P=0.139]、度拉鲁肽[OR=1.21,95%CI(0.57,2.58),P=0.616]、利西那肽[OR=1.27,95%CI(0.50,3.24),P=0.617]及阿必鲁肽[OR=0.70,95%CI(0.25,2.20),P=0.515],在骨折风险方面差异均无统计学意义。与对照组相比,GLP-1 RAs治疗对2型糖尿病患者骨折骨密度[OR=0.16,95%CI(-0.10,0.42),P=0.223]及血清钙[SMD=0.17,95%CI(-0.20,0.55),P=0.358]水平差异均无统计学意义。结论应用利拉鲁肽治疗2型糖尿病可降低患者骨折发生风险,而艾塞那肽等其他GLP-1 RAs及GLP-1 RAs总体骨折风险程度与对照组相似,且GLP-1 RAs对2型糖尿病患者骨密度及血清钙作用与对照组程度相似。     

肝硬化形成过程中大鼠肝组织结构上H1,H2受体的放射自显影研究

用光学放射自显影术对四氯化碳诱导的大鼠肝硬化形成过程中肝组织结构上的Ｈ１、Ｈ２受体进行定位研究。结果发现，Ｈ１、Ｈ２受体广泛分布于肝细胞和肝内血管壁上；肝硬化形成过程中，肝组织结构上的Ｈ１、Ｈ２受交对照组显著减少，小叶下肝静脉壁上的Ｈ１受体更明显，受体的上述变化可能是四氯化碳对肝细胞的毒性作用和血管壁上的受体发生了“下行调节”的结果。     

白介素-1受体拮抗剂对椎间盘基质代谢的影响

目的:探讨白介素-1受体拮抗剂(IL-1Ra)对双后肢大鼠椎间盘基质代谢的影响。方法:建立双后肢大鼠模型36只,随机分为实验组和对照组,每组18只,实验组从造模当天即予腹腔注射IL-1R(a50ng/kg),隔天重复注射至处死,对照组18只不予任何处理。于造模后1、3、6个月每组分别处死6只大鼠,完整取出L4/5椎间盘固定、切片,予SABC法进行免疫组化染色,并使用图像分析系统对纤维环中Ⅱ型胶原染色进行灰度值扫描,同理取出L5/6椎间盘,使用间苯三酚法测量蛋白多糖含量。结果:术后第1个月,实验组椎间盘髓核中Ⅱ型胶原灰度值及蛋白多糖含量分别为83.67±7.97和2.376±0.161,对照组分别为87.25±8.70和2.297±0.101,两组间无显著性差异(P>0.05);第3个月时实验组Ⅱ型胶原染色的灰度值及蛋白多糖含量分别为107.42±6.50和2.093±0.131,对照组分别为145.91±7.42和1.039±0.092,两组间比较有非常显著性差异(P<0.01);第6个月时实验组Ⅱ型胶原染色的灰度值及蛋白多糖含量分别为129.83±4.03和1.796±0.065,对照组分别为203.76±5.98和0.654±0.048,两组间比较有非常显著性差异(P<0.01)。结论:IL-1Ra对双后肢大鼠椎间盘基质降解有明显的抑制作用。     

Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers after renal transplantation

Abstract:  Renin-angiotensin system blockade retards the progression of diabetic and non-diabetic chronic kidney disease of the native kidneys. Though most patients suffer from a significant renal insufficiency (chronic kidney disease stage III) and a concomitant heart disease after renal transplantation, there is up to now no evidence supporting the use of inhibitors of the renin-angiotensin system in these patients. We wish to summarize the available evidence on the use of inhibitors of the renin-angiotensin system after renal transplantation. We specifically discuss potential beneficial as well as adverse effects of a renin-angiotensin system blockade. In addition, we review their influence on morphologic and biochemical markers as well as on renal function, graft and patient survival after renal transplantation.     

Angiotensin type-1 receptor blockade with losartan increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetes and nephropathy.

BACKGROUND: A growing body of evidence supports the concept that treatment with the newer angiotensin type-1 receptor blockers (ARBs) improves glucose homeostasis under conditions wherein it is impaired. Controversy exists, however, regarding the ability of losartan, an older ARB, to exert comparable improvement. The present study was undertaken to evaluate the effects of losartan on glucose homeostasis in subjects with type 2 diabetes and nephropathy. METHODS: Twenty-seven subjects with type 2 diabetic nephropathy were enrolled in this prospective, randomized, controlled study. Losartan (100 mg daily) or the calcium channel blocker amlodipine (10 mg daily) was administered for a period of 3 months. Fasting blood glucose, serum insulin and C-peptide concentrations were measured at baseline and at the end of the study. Oral glucose tolerance tests were performed to evaluate insulin sensitivity and beta-cell responsiveness. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Fasting blood glucose, HbA1c, AUC glucose, and urinary protein values were significantly decreased in the losartan group as compared with the amlodipine group (P<0.05). Furthermore, C-peptide concentrations, the insulin sensitivity index, and the insulin-to-glucose ratio were significantly increased after 3 months of therapy with losartan as compared to amlodipine (P<0.05). Reductions of fasting insulin concentrations and HOMA-IR were also observed for the losartan group; however, reductions were not significant when compared with the amlodipine group. CONCLUSION: In addition to reducing urinary protein excretion, losartan at 100 mg daily increases insulin sensitivity and improves glucose homeostasis in subjects with type 2 diabetic nephropathy.     

Effect of angiotensin II receptor blockers on insulin resistance in maintenance haemodialysis patients

AIM: Insulin resistance is a predictor of cardiovascular mortality in patients with end-stage renal disease. Although some clinical studies demonstrated that angiotensin II receptor blockers (ARB) improve insulin action in hypertensive patients, the role of ARB among patients with maintenance haemodialysis (MHD) remains controversial. The aim was to evaluate the effect of the ARB on insulin resistance in patients with MHD. METHODS: The authors examined 10 patients with MHD who regularly underwent haemodialysis at least two visits per week. After 4, 8 and 12 weeks of treatment with valsartan, blood pressure monitoring, insulin resistance by homeostasis model assessment (HOMA-IR), fasting plasma glucose, fasting plasma insulin and blood chemistries were measured and compared with baseline values. RESULTS: Ten patients with MHD aged 16-74 years participated in the study. The causes of end-stage renal disease included hypertension (four cases), diabetes (three cases), glomerulonephritis (one case) and unknown cause (two cases). Fasting insulin levels significantly reduced from 11.9 +/- 5.7 microU/mL to 8.0 +/- 6.8 microU/mL (P < 0.001), and HOMA-IR decreased significantly from 3.6 +/- 2.5 to 2.1 +/- 1.6 (P = 0.005). Averaged pre- and post-haemodialysis systolic and diastolic blood pressure did not significantly change. The treatment did not significantly change the levels of uric acid, albumin and urea clearance, except for a significant decrease in total cholesterol, low-density lipoprotein and intact-parathyroid hormone. CONCLUSION: The insulin resistance in patients with MHD is controlled by valsartan. ARB that ameliorate insulin resistance and hyperinsulinaemia could also provide effective options for preventing cardiovascular disease in patients with MHD.     

胆囊癌组织中c-erbB-2,nm23H_1癌基因产物的表达及意义

目的　探讨癌基因c erbB 2和肿瘤转移抑制基因nm2 3H1的产物在胆囊癌组织中的表达与其生物学意义。方法　采用免疫组织化学方法检测胆囊癌标本中c erbB 2和nm2 3H1蛋白的表达 ,分析其与临床病理间关系。结果　c erbB 2和nm2 3H1蛋白的阳性表达率分别为 43 75 % (2 8/ 6 4)和 5 4 6 9% (35 / 6 4)。Ⅳ期胆囊癌中c erbB 2蛋白阳性率 (80 % )明显高于其他期胆囊癌 (P <0 0 1) ,c erbB 2阳性组平均生存期差于阴性组 (P <0 0 5 )。而nm2 3H1蛋白的表达与肿瘤的分化、分期和预后无关。结论　在胆囊癌中 ,c erbB 2和nm2 3H1参与肿瘤发生发展过程 ,c erbB 2的表达与肿瘤的转移和预后有着密切关系。     

胆汁可溶型抑制性受体LAIR-1以及白介素-2受体监测在肝移植急性排斥反应中的意义

目的 探讨胆汁中sLAIR-1及IL-2R的表达在肝移植排斥反应中的意义.方法 连续3周应用双单克隆抗体夹心ELISA方法检测55例肝移植受者术后胆汁sLAIR-1及sIL2R水平.结果 在22例移植肝功能正常的受体中(对照组),胆汁sIL-2R在(23.1±3.5)～(55.1±6.1)ng/L范围之内呈较低水平的波动,sLAIR-1则波动于(3.2±1.1)～(6.1±1.4)ng/L范围之内,亦呈低水平表达.在急性排斥反应(AR)组,胆汁sIL-2R水平在排斥反应确诊前2 d为(116.1±10.3)ng/L,确诊前1 d则为(136.8±12.7)ng/L,均显著高于对照组(P＜0.01).在经激素冲击治疗3 d时则下降至(74.2±6.2)ng/L,明显低于确诊前1、2 d水平.在对照组,胆汁sLAIR-1在(3.2±1.1)～(6.1±1.4)ng/L范围之内呈较低水平的波动;在AR组确诊前3 d为(18.1±2.2)ng/L,确诊前2 d为(25.1±3.5)ng/L,确诊前1 d则为(31.1±5.5)ng/L,均显著高于对照组(P＜0.01);经激素冲击治疗3 d时,胆汁sLAIR-1水平下降至(8.1±2.5)ng/L,接近对照组水平,且sLAIR-1的下降早于sIL2R.结论 胆汁sLAIR-1在发生移植肝急性排斥反应的病人血清中有较高水平的表达,其波动较sIL-2R大,将二者联合进行监测,可望成为早期预测移植物排斥反应发生及转归的诊断指标.     

胆汁可溶型抑制性受体LAIR-1以及白介素-2受体监测在肝移植急性排斥反应中的意义

目的 探讨胆汁中sLAIR-1及IL-2R的表达在肝移植排斥反应中的意义.方法 连续3周应用双单克隆抗体夹心ELISA方法检测55例肝移植受者术后胆汁sLAIR-1及sIL2R水平.结果 在22例移植肝功能正常的受体中(对照组),胆汁sIL-2R在(23.1±3.5)～(55.1±6.1)ng/L范围之内呈较低水平的波动,sLAIR-1则波动于(3.2±1.1)～(6.1±1.4)ng/L范围之内,亦呈低水平表达.在急性排斥反应(AR)组,胆汁sIL-2R水平在排斥反应确诊前2 d为(116.1±10.3)ng/L,确诊前1 d则为(136.8±12.7)ng/L,均显著高于对照组(P＜0.01).在经激素冲击治疗3 d时则下降至(74.2±6.2)ng/L,明显低于确诊前1、2 d水平.在对照组,胆汁sLAIR-1在(3.2±1.1)～(6.1±1.4)ng/L范围之内呈较低水平的波动;在AR组确诊前3 d为(18.1±2.2)ng/L,确诊前2 d为(25.1±3.5)ng/L,确诊前1 d则为(31.1±5.5)ng/L,均显著高于对照组(P＜0.01);经激素冲击治疗3 d时,胆汁sLAIR-1水平下降至(8.1±2.5)ng/L,接近对照组水平,且sLAIR-1的下降早于sIL2R.结论 胆汁sLAIR-1在发生移植肝急性排斥反应的病人血清中有较高水平的表达,其波动较sIL-2R大,将二者联合进行监测,可望成为早期预测移植物排斥反应发生及转归的诊断指标.     

Prolongation of discordant renal xenograft survival by depletion of complement. Comparative effects of systemically administered cobra venom factor and soluble complement receptor type 1 in a guinea-pig to rat model

Abstract There is an increasing body of evidence to suggest that inhibition of complement activation may be a valuable approach to avert hyperacute rejection. In our study, the guinea-pig to rat discordant kidney xenograft model was adapted for the investigation of renal transplant function and an attempt was made to delay the hyperacute rejection using systemically administered cobra venom factor (CVF) and soluble complement receptor type 1 (sCR1). The saline-treated control recipients experienced a rapid transplant rejection with a xenograft survival averaging 10.5 ± 2.1 min. Administration of a single 60 U/kg i. v. bolus of CVF significantly prolonged renal graft survival to 20.4 ± 2.5 h, and by a single bolus of sCR1 (50 mg/kg) a prolongation of graft survival to 18.8 ± 2.3 h was achieved. The grafts functioned only over periods of 2.5 ± 0.3 and 2.3 ± 0.2 h, respectively. No complications of sCR 1 were noted. We concluded that complement inhibition by sCR 1 may be an important component in the therapeutic approach aiming at the prevention of hyperacute rejection in human organ transplantation.     

胃旁路术对2型糖尿病大鼠脂肪组织胰岛素受体β及胰岛素受体底物-1表达的影响

目的：观察胃旁路术对2型糖尿病大鼠（GK大鼠）脂肪组织胰岛素受体β（IR-β）及胰岛素受体底物-1（IRS-1）表达的影响,探讨其改善胰岛素抵抗的机制。方法30只8周龄雄性GK大鼠（糖尿病模型）采用数字表法分为手术组（行胃旁路手术）、假手术组（与手术组大鼠相同部位切断后原位端端吻合）和饮食配对组（与手术组大鼠同种和同等质量的饮食）,每组10只,另10只8周龄雄性SD大鼠作为空白对照组（自由进食及饮水）。检测术前与术后4周各组大鼠空腹血糖（FPG）和空腹胰岛素（FINS）水平,计算术前及术后4周胰岛素抵抗指数（HOMA-IR）,应用蛋白印迹（Western blot）技术检测各组术后4周脂肪组织IR-β和IRS-1的表达。结果手术组术后4周FPG及 HOMA-IR 较术前明显降低（分别为5.13±0.22比11.73±0.37,2.16±0.18比5.10±0.29;均P<0.05）,并能达到空白对照组术后水平（P>0.05）;而假手术组和饮食配对组较术前无显著变化（均P＞0.05）;术后4周手术组IR-β及IRS-1表达量均明显高于其他3组（均P<0.05）。结论胃旁路术能上调2型糖尿病大鼠胰岛素信号转导通路中IR-β及IRS-1的表达,改善脂肪组织胰岛素抵抗,提高胰岛素的敏感性。     

胆汁可溶型抑制性受体LAIR-1以及白介素-2受体监测在肝移植急性排斥反应中的意义

目的 探讨胆汁中sLAIR-1及IL-2R的表达在肝移植排斥反应中的意义.方法 连续3周应用双单克隆抗体夹心ELISA方法检测55例肝移植受者术后胆汁sLAIR-1及sIL2R水平.结果 在22例移植肝功能正常的受体中(对照组),胆汁sIL-2R在(23.1±3.5)～(55.1±6.1)ng/L范围之内呈较低水平的波动,sLAIR-1则波动于(3.2±1.1)～(6.1±1.4)ng/L范围之内,亦呈低水平表达.在急性排斥反应(AR)组,胆汁sIL-2R水平在排斥反应确诊前2 d为(116.1±10.3)ng/L,确诊前1 d则为(136.8±12.7)ng/L,均显著高于对照组(P＜0.01).在经激素冲击治疗3 d时则下降至(74.2±6.2)ng/L,明显低于确诊前1、2 d水平.在对照组,胆汁sLAIR-1在(3.2±1.1)～(6.1±1.4)ng/L范围之内呈较低水平的波动;在AR组确诊前3 d为(18.1±2.2)ng/L,确诊前2 d为(25.1±3.5)ng/L,确诊前1 d则为(31.1±5.5)ng/L,均显著高于对照组(P＜0.01);经激素冲击治疗3 d时,胆汁sLAIR-1水平下降至(8.1±2.5)ng/L,接近对照组水平,且sLAIR-1的下降早于sIL2R.结论 胆汁sLAIR-1在发生移植肝急性排斥反应的病人血清中有较高水平的表达,其波动较sIL-2R大,将二者联合进行监测,可望成为早期预测移植物排斥反应发生及转归的诊断指标.     

Dose-reducing H2 receptor antagonists in the presence of low glomerular filtration rate: a systematic review of the evidence.

BACKGROUND: While it is recommended that H2 receptor antagonists (H2RAs) be dose reduced in the presence of low glomerular filtration rate (GFR), in practice such adjustments often do not occur. We reviewed the evidence for this recommendation. METHODS: We searched multiple medical reference databases for relevant cohort studies and randomized clinical trials. Studies that enrolled five or more participants with low GFR who also received at least one unadjusted dose of an H2RA, and who were compared with controls were included. Data were abstracted on study and participant characteristics and drug-related adverse effects. Pharmacokinetic measures were pooled using meta-analysis. RESULTS: A total of 22 articles were included, comprising 19 unique cohort studies. With declining GFR, there was a significant increase in the area under the curve (AUC) and elimination half-life (t(1/2)) of the serum drug concentration of H2RAs (P < 0.001). Compared with a GFR >80 ml/min/1.73 m2, drug AUC increased by 200% when the GFR was 30 ml/min/1.73 m2, and by 300% when the GFR was 20 ml/min/1.73 m2. In hospitalized patients with low GFR, reducing the interval dose of intravenous H2RA was associated with fewer adverse reactions. The gastro-protective effects of H2RAs were similar with reduced and unadjusted doses. CONCLUSIONS: Reducing the dose of H2RAs in persons with low GFR will decrease drug expenditure and may prevent adverse events, without a change in efficacy. Quality assurance programmes, which improve deficiencies in H2RAs prescribing, appear justified.