阳和汤加减方治疗脾肾阳虚型系统性硬皮病临床疗效观察及机制探讨

The Clinical Efficacy and Mechanism of Yanghe Decoction on Spleen-Kidney Yang Deficiency Systemic Scleroderma Patients

[目的]观察阳和汤加减治疗脾肾阳虚型硬化期系统性硬皮病的临床疗效,并初步探讨其疗效机制。[方法]采用随机对照试验,60例患者被分为治疗组和对照组各30例。治疗(阳和汤)组,口服中药阳和汤加减,每日1剂,分早晚口服;对照(D-青霉胺)组,口服D-青霉胺,开始剂量250mg/d,1周后逐渐增加剂量至0.75 g/d-1g/d,并同时服用维生素B6和维生素B1,每次各2片,3次/d,减少D-青霉胺的毒副作用。所有病例每2周复诊1次,治疗前后对患者皮肤厚度评分,同时在治疗前及治疗第1、2、3月分别检测患者抗核抗体(antinuclear antibodies,ANA)谱、抗着丝点抗体(anti-centromere antibody,ACA)、血沉(Erythrocyte Sedimentation Rate,ESR)、结缔组织生长因子(connective tissue growth factor,CTGF)、血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)、基质金属蛋白酶类抑制剂-1(tissue inhibitor of metalloproteinase-1,TMP-1)、基质金属蛋白酶类抑制剂-2(tissue inhibitor of metalloproteinase-2,TMP-2)等实验室指标,3个月后判定疗效。[结果]阳和汤加减治疗脾肾阳虚型硬化期系统性硬皮病总有效率达70.00%,优于对照组(P<0.05);脾肾阳虚型硬化期系统性硬皮病患者自身抗体中ACA转阴率明显高于对照组(P<0.05);阳和汤加减能降低皮肤硬度积分(P<0.05);阳和汤组患者ESR下降明显优于对照组(P<0.05),且能降低硬皮病患者CTGF水平(P<0.05)、下调血清TIMP-1及TIMP-2(P<0.01),上调血清MMP-1水平(P<0.05)。[结论]阳和汤加减治疗脾肾阳虚型硬化期系统性硬皮病疗效确切,其机理可能与促使自身抗体转阴和抑制胶原合成有关。

[Objective] To observe the clinical effect of Yang-he decoction for treatment of spleen and kidney deficiency of systemic sclerosis scleroderma, and to explore its effect mechanism. [Methods] A randomized controUed trial, 60 patients were divided into a treatment group and a control group of 30 cases. Treatment（Yang-he soup） group, male and oral medicine decoction, a daily morning and evening orally; control（D-penicillamine） group, oral D- penicillamine, a starting dose of 250mg/d, 1 week later gradually increase the dose to 0.75 g/d-lg/d, while vitamin B6 and vitamin B1, one time each two, three times a day to reduce the side effects of D-penicillamine. All patients were visited once every two weeks, before and after treatment in patients with the skin thickness score, while before treatment and 1, 2, 3 months were detected in patients with ANA March spectrum, anti-centromere antibody, erythrocyte sedimentation rate, connective tissue growth factor, serum matrix metalloproteinase-1, matrix metalloproteinase inhibitors of matrix metalloproteinase inhibitor-2 and other laboratory parameters, three months later to determine efficacy. [Results] Yang-he decoction for treatment of spleen and kidney deficiency in systemic scleroderma of hard state total effective rate was 70.0（00, better than the control group（P〈0.05）; scleroderma autoantibodies ACA negative rate was significantly higher（P〈0.05）; Yang-he decoction can reduce the skin hardness integral（P〈0.05）; male and ESR decreased in patients treated group than the control group（P〈0.05）, and can reduce scleroderma patients CTGF levels（P〈0.05）, lower serum TIMP-1 and TIMP-2 （P〈0.01）, increase serum levels of MMP-I（P〈O.05）. [Conclusion] Yang-he decoction for treatment of spleen and kidey deficiency systemic scleroderma in hard state efficacy, its mechanism may be inducing autoantibody negative and inhibition of collagen synthesis.