加味四妙方抗高尿酸血症及痛风性关节炎药效学分析

Pharmacological Analysis of Modified Simiao Powder on Gouty Arthritis and Hyperuricemia

目的:考察加味四妙方抗高尿酸血症及痛风性关节炎的作用。方法:SD大鼠60只随机分为空白组、模型组、别嘌醇组(60 mg·kg-1)、加味四妙方高、中、低剂量组(24,12,6 g·kg-1)6组(n=10)。除空白组外,其他组喂食次黄嘌呤饲料,喂饲后第1,3,5天sc氧嗪酸钾复制高尿酸血症模型,于喂饲后第1天ig给药,连续5 d。检测血尿酸(UA),尿UA水平及血液、肝脏黄嘌呤氧化酶(XO)活性。新西兰兔40只随机分为模型组、秋水仙碱组(0.3 mg·kg-1)、加味四妙方高、中、低剂量组(12,6,3 g·kg-1)5组(n=8)。连续ig给药5 d后,各组家兔膝关节腔注射尿酸钠结晶(MSU)诱导痛风性关节炎模型。检测关节肿胀度,关节液白细胞计数(WBC),白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)水平及关节囊、滑膜组织病变程度。结果:高尿酸血症模型大鼠与空白组比较,血UA,尿UA及血液XO,肝脏XO均明显上升(P<0.01);加味四妙方高、中、低剂量组能降低高尿酸血症模型大鼠血UA,尿UA(P<0.01,P<0.05),且能显著降低血液XO(P<0.01)。对由MSU引起的家兔膝关节肿胀,在致炎后1,3,5 h,痛风模型家兔与空白组比较,关节液WBC及IL-1β,IL-6含量均明显上升(P<0.01);加味四妙方高、中剂量组能抑制其肿胀度(P<0.01,P<0.05),显著降低关节液WBC及IL-1β,IL-6含量(P<0.01,P<0.05),且高剂量组能减轻关节组织病变程度(P<0.05)。结论:加味四妙方对高尿酸血症模型大鼠有降UA作用,并对痛风模型家兔有良好的抗炎作用,其作用机制可能与降低XO活性,抑制关节IL-1β,IL-6合成与释放有关。

Objective： To explore the effects of Modified Simiao powder on gouty arthritis and hyperurieemia. Method： Sixty SD rats were randomly divided into 6 groups： the control group, model group, 24, 12, 6 g ·kg^-1 Modified Simiao powder groups and allopurinol group, 10 rats in each group. The rat hyperuricemia model was established by hypoxanthine and oteracil potassium, the level of serum and urinary uric acid, the activity of serum and liver xanthine oxidase were detected. Forty rabbits were randomly divided into 5 groups： the model group, 12, 6, 3 g ·kg^-1 Modified Simiao powder groups and colchicine group （n = 8）. Rabbit acute gouty arthritis model was established by monosodium urate （MSU） intraarticular injection, the joint swell and articular lesions degree, white blood cell count, interleukin （IL）-1β and IL-6 in synovia were also measured. Result： Modified Simiao powder 24, 12, 6 g·kg^-1 ig could significantly reduce the serum and urinary uric acid level in byperuricemic rat （ P 〈 0. 01, P 〈 0.05 ）, together with decreasing liver xanthine oxidase activity （ P 〈 0.01 ）. Modified Simiao powder 12, 6 g ·kg^-1 ig could obviously restrain the joint swelling degree in the gouty arthritis modeling rabbits 1, 3, 5 h after modeling （P〈0.01, P 〈0.05）. White blood cell （WBC）, IL-1/3 and IL-6 levels were also decreased significantly after administration （P 〈 0. 01, P 〈 0.05） , meanwhile, 12 g·kg^-1 ig could significantly reduce the articular lesions degree （P 〈 0.05）. Conclusion： Modified Simiao powder could obviously decrease urea acid （UA） of hyperuricaeidemia modeling rats, and anti-inflammatory of gouty arthritis modeling rabbist. The mechanisms of its effects may liet in decreasing xanthine oxidase （XO） activity and restraining the synthesis of IL-1β, IL-6 in joint.