他汀类降脂药治疗类风湿关节炎早期肾动脉损害大鼠的机制探讨

Mechanism of statin drugs in treating early renal artery damage in rats with rheumatoid arthritis

目的探讨单独应用他汀类降脂药物治疗及保护类风湿性关节炎早期肾动脉损害的机制。方法 30只雄性Wistar大鼠分为空白对照组(N组)、类风湿关节炎组(RA组)、类风湿关节炎阿托伐他汀治疗组(T组),每组10只,实验共观察8周。实验测量这3组大鼠的肾动脉内皮依赖性舒张功能、血脂各指标、血清妊娠相关血浆蛋白-A(PAPP-A)、肿瘤坏死因子-α(TNF-α)及白介素-1β(L-1β)。结果实验结束时,类风湿关节炎组的TC、TG、LDL-C、PAPP-A、TNF-α及IL-1β较空白对照组明显增高(P<0.01),类风湿关节炎组的大鼠肾动脉内皮依赖性舒张率和HDL-C较空白对照组明显减低(P<0.01);类风湿关节炎阿托伐他汀治疗组的AI值、TC、TG、LDL-C、PAPP-A、TNF-α及IL-1β较类风湿关节炎组明显降低(P<0.01),类风湿关节炎阿托伐他汀治疗组的大鼠肾动脉内皮依赖性舒张率和HDL-C较类风湿关节炎组明显增高(P<0.01)。结论类风湿关节炎可使大鼠出现关节炎症、血清炎症因子增高、血清PAPP-A增高、脂质代谢紊乱及早期肾动脉损害;单独应用他汀类降脂药物能显著改善类风湿关节炎造成的关节炎症、血清炎症因子、血清PAPP-A、脂质代谢紊乱及早期肾动脉损害。他汀类降脂药除了有降脂的作用外,还可能通过其抗炎作用改善类风湿关节炎造成的早期肾动脉内皮细胞功能紊乱,延缓类风湿关节炎造成的肾动脉粥样硬化进展,从而减少肾血管性高血压及缺血性肾病的发生。阿托伐他汀可能是通过改善炎症反应、降低血清PAPP-A及调节脂质代谢紊乱来保护治疗类风湿关节炎早期肾动脉损害的。

Objective To investigate the mechanism of statin in treating and protecting early renal artery damage in rats with rheumatoid arthritis（RA）. Methods Totally 30 male Wistar rats were randomly divided into a control group（N group）, a rheumatoid arthritis group（RA group）, and an atorvastatin treatment group of rheumatoid arthritis（T group）, with 10 rats in each group. The experiment was observed for 8 weeks. The renal arterial endothelial dependent diastolic function, blood lipid, pregnancy associated plasma protein-A（PAPP-A）, TNF-α and IL-1β were respectively measured in the 3 groups. Results Compared with the blank control group, the TC, TG, LDL-C, PAPP-A, TNF-α and IL-1β increased significantly in the rheumatoid arthritis group（P〈0.01）, while the rheumatoid arthritis group rat renal artery endothelium dependent relaxation rate and HDL-C in the rheumatoid arthritis group were significantly decreased（P〈0.01）. The AI value, TC, TG, LDL-C, PAPP-A, TNF-α and IL-1β in the atorvastatin treatment group decreased more significantly than those of the rheumatoid arthritis group（P〈0.01）. The rat renal artery endothelium dependent relaxation rate and HDL-C in the atorvastatin treatment group increased more significantly than those of the rheumatoid arthritis group（P〈0.01）. Conclusion Rheumatoid arthritis can cause joints inflammation in rats, increase serum inflammatory factors and serum PAPP-A, and cause lipid metabolism disorders and early renal artery damage. Statins alone can significantly improve the arthritis caused by rheumatoid arthritis, serum inflammatory factors, serum PAPP-A, lipid metabolism disorders and early renal artery damage. Besides lipid-lowering, statins may also have antiinflammatory effects on rheumatoid arthritis caused by renal artery endothelial cell function disorder, delay rheumatoid arthritis caused by renal progression of atherosclerosis, thereby reducing renal vascular hypertension and the incidence of ischemic nephropathy. Atorvastatin may protect the early renal artery damage in the treatment of rheumatoid arthritis by improving inflammatory reaction, reducing serum PAPP-A and regulating lipid metabolism disorders.