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目的:通过观察大黄?虫丸对泛素-蛋白酶体系统中主要组分泛素(Ub)、泛素活化酶(Ub E1)及20S蛋白酶体的影响,探讨该方剂防治AS的作用机制。方法:雄性Wistar大鼠45只,随机分为正常对照组、模型对照组、辛伐他汀5mg/kg组、大黄?虫丸700 mg/kg剂量组、大黄?虫丸1400 mg/kg剂量组。采用高脂饲料喂养联合大剂量维生素D3腹腔注射方式复制大鼠AS模型。造模开始即给予相应剂量实验及阳性对照药物灌胃,连续观察12周。断头取血,检测血浆20S蛋白酶体;剖取主动脉,免疫组织化学法观察大鼠泛素(Ub)表达;并采用Western blot、RT-PCR方法检测主动脉泛素活化酶(Ub E1)蛋白含量及mRNA表达。结果:大黄?虫丸1400 mg/kg剂量组泛素(Ub)、泛素活化酶(Ub E1)蛋白含量及mRNA表达均比模型对照组减弱,20S蛋白酶体活性增强。结论:大黄?虫丸防治AS的机制可能与阻抑泛素-蛋白酶体系统,发挥蛋白酶体抑制剂的作用有关。
OBJECTIVE: To investigate the effect of rhubarb pellets on the ubiquitin-ubiquitin-activating enzyme (Ub) and 20S proteasome in the ubiquitin-proteasome system and to explore the mechanism of action of this formula on the prevention and treatment of AS. Methods: Forty-five male Wistar rats were randomly divided into normal control group, model control group, simvastatin 5 mg / kg group, rhubarb and pestle pill 700 mg / kg and rhubarb and pestle pill 1400 mg / kg. The model of AS was established by intraperitoneal injection of high-fat diet and high-dose vitamin D3. At the beginning of modeling, the corresponding dose experiment and positive control drug were given intragastrically for 12 weeks. The blood samples were decapitated to detect the plasma 20S proteasome. The aorta was dissected and the expression of Ub in rats was observed by immunohistochemical method. The aorta ubiquitin-activating enzyme (Ub E1) was detected by Western blot and RT- Protein content and mRNA expression. Results: The contents and mRNA expressions of ubiquitin (Ub) and ubiquitin-activated enzyme (Ub E1) in the rhubarb and pestle pill 1400 mg / kg group were weaker than those in the model control group, and the activity of 20S proteasome was enhanced. CONCLUSION: The mechanism of rhubarb and insect pest control AS may be related to inhibiting the ubiquitin-proteasome system and exerting the function of proteasome inhibitor.