哌唑嗪联合缬沙坦治疗α1和AT_1受体自身抗体阳性的2型糖尿病合并难治性高血压患者的疗效评估

Clinical evaluation of valsartan and prazosin in treatment of the positive α1-adrenergic and AT_1 receptor patients with type 2 diabetes mellitus and refractory hypertension

目的观察哌唑嗪联合缬沙坦治疗α1和AT_1受体自身抗体阳性的T2DM合并难治性高血压(R HT)的疗效。方法以合成的α1和AT_1受体多肽片段为抗原,应用ELISA技术,检测282例人血清抗α1和AT_1受体自身抗体:DM合并R-HT者117例(DM+R-HT组),DM合并非R-HT 119例(DM+NR-HT组),正常对照46名(NC组)。其中DM+R-HT组中抗α1和AT_1受体自身抗体均阳性者37例为RAAb(+)组,两受体自身抗体均阴性者30例为RAAb(-)组。RAAb(+)组和RRAb(-)组均给予缬沙坦80mg,日一次,口服;哌唑嗪1mg,日三次,口服;尼群地平10mg,日三次,口服;双氯噻嗪12.5mg,日一次,口服;阿司匹林100mg,日一次,口服;观察两组降压疗效。结果 DM+R-HT组抗α1和AT_1受体自身抗体阳性率明显高于DM+NR-HT组和NC组(P均<0.01)。RAAb(+)组降压疗效明显优于RAAb(-)组。临床降压效果评定,RAAb(+)组总有效率为89.2%,RAAb(-)组为60.0%,两组比较差异有统计学意义(P<0.05)。结论对糖尿病合并难治性高血压,通过抗α1和AT_1受体自身抗体检测,有针对性地选择降压药物哌唑嗪和缬沙坦,降压疗效好且较安全。

Objective To investigate the therapeutic effects of valsartan and prazosin on the positive AT1 receptor and α1-adrenergic receptor patients with 2 type diabetes mellitus and refractory hypertension. Methods The epitopes of the second extracellular loop of α2 receptor and AT1 receptor were synthesized and used respectively to screen sera autoantibodies from patients with type 2 diabetes mellitus and refractory （n= 117） or non-refractory （n= 119） hypertension, and from control group （n=46）. The two groups of patients with positive and negative autoantibodies against α1 and AT-1 receptor were given the similar drugs of valsartan 80mg qd, prazosin 1mg tid, aspirin 100mg qd; nitrendipine 10mg tid,hydrochlorothiazide 12.5mg for six weeks. Results In the patients with T2DM and refractory hypertension, the positive rates of the autoantibodies against αl1 receptor and AT1 receptor were 31.6% （37/117） and 42.7 % （50/117） respectively,higher than group of T2DM with non-refractory hypertension （22.7% ,17.6% respectively） and than control group （7.5%, 10.0% respectively） （all P〈 0.05）. The total hypotensively effective rate of was 89. 2% for RAAb（＋） group and 60. 0% for RAAb（- ） group （all P〈 0.05）. Conclusions Autoantibodies against al and ATe-receptor may play important roles in the pathogenesis of type 2 diabetes mellitus with refractory hypertension. Valsartan and prazosin are effective and safe in the treatment of type 2 diabetes mellitus with refractory hypertension.