糖尿病肾病合并高血压患者的抗血管紧张素Ⅱ受体1型自身抗体

目的探讨抗血管紧张素Ⅱ受体1型(AT1受体)自身抗体在糖尿病肾病(DN)合并难治性高血压发病中的作用及临床干预。方法以合成的和AT1受体多肽片段为抗原,应用ELISA技术,检测DN合并2级以上高血压者166例,其中DN合并难治性高血压91例,DN合并非难治性高血压75例,正常对照组40例,DN合并难治性高血压抗AT1受体自身抗体阳性的患者随机分为治疗组及对照组。1)对照组:卡托普利25~50mg,3次/d;尼群地平10~20mg,1次/6h;美托洛尔12.5~25.0mg,3次/d;肠溶阿司匹林100mg/d。2)治疗组在上述治疗基础上加服缬沙坦80~160mg/次.d。结果DN合并高血压组抗AT1受体自身抗体阳性总的阳性率为49.5%,正常对照组阳性率为10.0%,两组比较差异有非常显著意义(P<0.01)。DN合并难治性高血压91例,AT1受体自身抗体阳性率为78.0%(71/91),DN合并非难治性高血压75例,阳性率为14.6%(11/75),两组比较异差有统计学意义。缬沙坦治疗组降压疗效明显优于对照组,临床降压疗效评定,治疗组总有效率为85.6%,明显高于对照组的33.3%,两组比较具有非常显著性差异(P<0.01)。结论抗AT1受体自身抗体可能参与DN合并难治性高血压的发病,AT1受体阻断剂缬沙坦是治疗DN合并难治性高血压有效降压药物之一。

Autoantibody Against AT_1 Receptor in Diabetic Nephropathy with Refractory Hypertension

Objective To investigate the mechanism of the autoantibody against AT_1 receptor in diabetic nephropathy(DN) with refractory hypertension. Methods The epitopes of the second extracellular loop of AT_ 1 receptor (165-191) was synthesized. 166 patients with DN complicated with hypertension underwent sera autoantibody screening,including 91 patients with refractory hypertension(RH) and 75 patients with non-refractory hypertension. 40 healthy subjects served as control. 71 patients with DN and RH were randomized to receive conventional antihypertensive therapy(captopril, nitrendipine, metoprolol and aspirin, n=30) or adding valsartan(80-160 mg/d) to conventional therapy (n=41) for 12 weeks. Results 166 DN patients with hypertension had 49.4% positive rate of autoantibodies against AT_1 receptor in relative to healthy donors of 10%(P<0.01). Moreover, the positive rate was even higher in DN with RH(78.0%) as compared with DN patients with non-RH(14.7%, P<0.01). Valsartan significantly decreased SBP and DBP(-57/24 mm Hg)in DN with RH while in the conventional thrapy group the reduction of BP was of -15/15 mm Hg only (P<0.01). 63.4% patients in valsartan group but only 33.3% in conventional therapy group reached the goal BP(P<0.05). Conclusion The finding suggest that the autoantibodies against AT_1 receptor may play important roles in the pathogenesis of the diabetic nephropathy with refractory hypertension. Valsartan was shown to be effective and safe in thetreatment of diabetic nephropathy with refractory hypertension.