Background Studies have confirmed that angiotensin II receptor blocker （ARB） and angiotensin converting enzyme inhibitors （ACEI） in the treatment of diabetic nephropathy （DN） has special advantages. We observed ...Background Studies have confirmed that angiotensin II receptor blocker （ARB） and angiotensin converting enzyme inhibitors （ACEI） in the treatment of diabetic nephropathy （DN） has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive β1-adrenergic and anti-angiotensin II type 1 （AT1） receptor antibody. Methods The epitopes of the second extracellular loop of β1 receptor （197-222） and AT1 receptor （165-191）, were synthesized and used respectively to screen serum autoantibodies from patients with DN （n=371, group A）, diabetes mellitus （DM） without renal failure （n=107, group B） and healthy blood donors （n=47, control, group C） by enzyme-linked immunosorbent assay （ELISA）. Metoprolol tartrate 25-50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 rag, once a day, and nitrendipine 10-20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment. Results In DN patients, the positive rate of the autoantibodies against β1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls （all P 〈0.01）. Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly （P 〈0.01） in DN patients with positive autoantibodies. Conclusions The findings suggest that these autoantibodies against β1 and ATl-receptor may play important roles in the pathogenesis of DN. Valsartan and metoDrolol tartrate are effective and safe in the treatment of DN.展开更多
目的研究比索洛尔对腹主动脉结扎所致慢性心力衰竭大鼠β_1肾上腺素能受体(β_1-AR)心功能的调节作用。方法 SD 大鼠40只,随机分为4组,即腹主动脉缩窄(COA)组;COA+比索洛尔组;假手术组;假手术+比索洛尔组。采用超声心动图和心室插管法...目的研究比索洛尔对腹主动脉结扎所致慢性心力衰竭大鼠β_1肾上腺素能受体(β_1-AR)心功能的调节作用。方法 SD 大鼠40只,随机分为4组,即腹主动脉缩窄(COA)组;COA+比索洛尔组;假手术组;假手术+比索洛尔组。采用超声心动图和心室插管法评估心功能,ELISA_法检测各组大鼠血浆去甲肾上腺素(NE)水平,RIA 法检测心肌腺苷酸环化酶(AC)活性,通过 RT-PCR 检测心肌β_1-AR、β肾上腺素能受体激酶1(β-ARK1)和 Gi 蛋白 mRNA 的表达变化,Western blot 检测β_1-AR 蛋白水平的表达变化。结果 COA 组大鼠心功能恶化,血浆 NE 水平明显升高,β_1-AR mRNA 表达减少、β-ARK1和 Gi 蛋白 mRNA 表达增加,β_1-AR 的蛋白水平表达减少,AC 活性明显下降;比索洛尔明显改善大鼠心功能[射血分数:COA+比索洛尔组:(66.7±8.4)%比 COA 组:(43.3±7.7)%,P<0.05],降低血浆 NE 水平[COA+比索洛尔组:(570.2±41.2)pg/mL 比 COA 组:(908.24±75.10)pg/mL,P<0.05],增高β_1-AR mRNA 表达[COA+比索洛尔组:(57.5±5.4)比 COA 组:(44.9±4.2)P<0.05],降低β-ARK1和 Gi 蛋白 mRNA 表达[β-ARK1:COA+比索洛尔组:(38.0±3.2)比 COA 组:(52.4±4.1),P<0.05;Gi 蛋白:COA+比索洛尔组:(72.8±5.8)%比 COA 组:(102.9±8.5)%,P<0.05],Western blot检测显示比索洛尔也增加β_1-AR 的蛋白水平表达[COA+比索洛尔组:(59.2±4.8)%比 COA 组:(30.9±2.3)%,P<0.05],AC 活性明显升高。结论比索洛尔能够调节慢性心力衰竭大鼠β_1-AR 信号转导通路,改善心功能,延缓心力衰竭进展。展开更多
目的探讨扩张型心肌病患者血清中针对β1-肾上腺素受体细胞外第二环（the second extracellular loop of β1-adrenoceptor，β1-AR-ECⅡ）功能表位肽段的自身抗体（β1—AA）对大鼠CD4＋ T淋巴细胞增殖能力的影响。方法采用亲和柱纯化...目的探讨扩张型心肌病患者血清中针对β1-肾上腺素受体细胞外第二环（the second extracellular loop of β1-adrenoceptor，β1-AR-ECⅡ）功能表位肽段的自身抗体（β1—AA）对大鼠CD4＋ T淋巴细胞增殖能力的影响。方法采用亲和柱纯化试剂盒提纯扩张型心肌病（DCM）患者血清中的β1-AA；利用免疫磁珠分选技术分离出大鼠外周血单核细胞中的CD4＋ T淋巴细胞，流式细胞技术检测CD4＋ T细胞的阳性率；采用CCK-8试剂盒检测细胞增殖能力；流式细胞术检测CD4＋ ／CD8＋T淋巴细胞的比值。结果经免疫磁珠分选后CD4＋T淋巴细胞的阳性率为97．7％；β1-AA可浓度依赖性抑制CD3／CD28刺激的CD4＋T淋巴细胞增殖；β1-AA被β1-AR—ECⅡ中和后，该效应消失；β1-AR特异性阻断剂美托洛尔可完全阻断该抑制效应；β1-AA作用于总T淋巴细胞24h后，CD4＋／CD8＋T淋巴细胞比值没有发生明显改变。结论从DCM患者血清中提取的β1-AA可能通过CD4＋T淋巴细胞表面的β1-AR途径，导致该细胞增殖能力下降。提示β1-AA可能会直接减少T淋巴细胞的数量，使得T淋巴细胞功能下降，进而导致免疫系统紊乱，参与DCM的发生发展。展开更多
基金This study was supported by a grant from the Natural Science Foundation of Hubei Province （No. 2002AB 116）.
文摘Background Studies have confirmed that angiotensin II receptor blocker （ARB） and angiotensin converting enzyme inhibitors （ACEI） in the treatment of diabetic nephropathy （DN） has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive β1-adrenergic and anti-angiotensin II type 1 （AT1） receptor antibody. Methods The epitopes of the second extracellular loop of β1 receptor （197-222） and AT1 receptor （165-191）, were synthesized and used respectively to screen serum autoantibodies from patients with DN （n=371, group A）, diabetes mellitus （DM） without renal failure （n=107, group B） and healthy blood donors （n=47, control, group C） by enzyme-linked immunosorbent assay （ELISA）. Metoprolol tartrate 25-50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 rag, once a day, and nitrendipine 10-20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment. Results In DN patients, the positive rate of the autoantibodies against β1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls （all P 〈0.01）. Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly （P 〈0.01） in DN patients with positive autoantibodies. Conclusions The findings suggest that these autoantibodies against β1 and ATl-receptor may play important roles in the pathogenesis of DN. Valsartan and metoDrolol tartrate are effective and safe in the treatment of DN.
文摘目的研究比索洛尔对腹主动脉结扎所致慢性心力衰竭大鼠β_1肾上腺素能受体(β_1-AR)心功能的调节作用。方法 SD 大鼠40只,随机分为4组,即腹主动脉缩窄(COA)组;COA+比索洛尔组;假手术组;假手术+比索洛尔组。采用超声心动图和心室插管法评估心功能,ELISA_法检测各组大鼠血浆去甲肾上腺素(NE)水平,RIA 法检测心肌腺苷酸环化酶(AC)活性,通过 RT-PCR 检测心肌β_1-AR、β肾上腺素能受体激酶1(β-ARK1)和 Gi 蛋白 mRNA 的表达变化,Western blot 检测β_1-AR 蛋白水平的表达变化。结果 COA 组大鼠心功能恶化,血浆 NE 水平明显升高,β_1-AR mRNA 表达减少、β-ARK1和 Gi 蛋白 mRNA 表达增加,β_1-AR 的蛋白水平表达减少,AC 活性明显下降;比索洛尔明显改善大鼠心功能[射血分数:COA+比索洛尔组:(66.7±8.4)%比 COA 组:(43.3±7.7)%,P<0.05],降低血浆 NE 水平[COA+比索洛尔组:(570.2±41.2)pg/mL 比 COA 组:(908.24±75.10)pg/mL,P<0.05],增高β_1-AR mRNA 表达[COA+比索洛尔组:(57.5±5.4)比 COA 组:(44.9±4.2)P<0.05],降低β-ARK1和 Gi 蛋白 mRNA 表达[β-ARK1:COA+比索洛尔组:(38.0±3.2)比 COA 组:(52.4±4.1),P<0.05;Gi 蛋白:COA+比索洛尔组:(72.8±5.8)%比 COA 组:(102.9±8.5)%,P<0.05],Western blot检测显示比索洛尔也增加β_1-AR 的蛋白水平表达[COA+比索洛尔组:(59.2±4.8)%比 COA 组:(30.9±2.3)%,P<0.05],AC 活性明显升高。结论比索洛尔能够调节慢性心力衰竭大鼠β_1-AR 信号转导通路,改善心功能,延缓心力衰竭进展。
文摘目的探讨扩张型心肌病患者血清中针对β1-肾上腺素受体细胞外第二环（the second extracellular loop of β1-adrenoceptor，β1-AR-ECⅡ）功能表位肽段的自身抗体（β1—AA）对大鼠CD4＋ T淋巴细胞增殖能力的影响。方法采用亲和柱纯化试剂盒提纯扩张型心肌病（DCM）患者血清中的β1-AA；利用免疫磁珠分选技术分离出大鼠外周血单核细胞中的CD4＋ T淋巴细胞，流式细胞技术检测CD4＋ T细胞的阳性率；采用CCK-8试剂盒检测细胞增殖能力；流式细胞术检测CD4＋ ／CD8＋T淋巴细胞的比值。结果经免疫磁珠分选后CD4＋T淋巴细胞的阳性率为97．7％；β1-AA可浓度依赖性抑制CD3／CD28刺激的CD4＋T淋巴细胞增殖；β1-AA被β1-AR—ECⅡ中和后，该效应消失；β1-AR特异性阻断剂美托洛尔可完全阻断该抑制效应；β1-AA作用于总T淋巴细胞24h后，CD4＋／CD8＋T淋巴细胞比值没有发生明显改变。结论从DCM患者血清中提取的β1-AA可能通过CD4＋T淋巴细胞表面的β1-AR途径，导致该细胞增殖能力下降。提示β1-AA可能会直接减少T淋巴细胞的数量，使得T淋巴细胞功能下降，进而导致免疫系统紊乱，参与DCM的发生发展。
