Yan Yu, Zhang Zhihui, Chen Yucai, Hou Biyu, Liu Kang, Qin Hailin, Fang Lianhua, Du Guanhua
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.
Front Pharmacol. 2020 Jun 19;11:929. doi: 10.3389/fphar.2020.00929. eCollection 2020.
Systemic lupus erythaematosus (SLE) is a chronic multi-system autoimmune disease with a high prevalence of kidney and cardiovascular complications. Considering that Rho-associated coiled-coil-containing protein kinases (ROCKs) play important roles in SLE, inflammation, and cardiovascular disease, we hypothesized that coptisine, which has been found to inhibit ROCKs, may have an effect on SLE. The effect of coptisine was assessed in female BALB/c mice intraperitoneally injected with 0.5 mL of pristane. Serum autoantibodies were tested every month, blood pressure was measured every 2 months, and serum inflammatory markers, spleen pathologic characteristics, renal injury and vascular function were observed at 6 months. The results showed that coptisine decreased the levels of serum autoantibodies and serum inflammatory markers in the SLE mice, improved the pathologic characteristics of the spleen, and simultaneously improved renal injury, decreased inflammatory responses in the kidneys, reduced blood pressure, and improved vascular endothelial function. Western blot assays revealed that inhibiting the activation of the NF-κB and Rho/ROCK signalling pathways and downstream signalling molecules might be the potential mechanisms of the effects of coptisine. Our findings suggest that therapy with coptisine may be a strategy for preventing SLE and ameliorating associated kidney and cardiovascular complications.
系统性红斑狼疮(SLE)是一种慢性多系统自身免疫性疾病,肾脏和心血管并发症的患病率很高。鉴于含Rho相关卷曲螺旋结构域蛋白激酶(ROCKs)在SLE、炎症和心血管疾病中发挥重要作用,我们推测已发现具有抑制ROCKs作用的黄连碱可能对SLE有影响。在腹腔注射0.5 mL pristane的雌性BALB/c小鼠中评估黄连碱的作用。每月检测血清自身抗体,每2个月测量血压,并在6个月时观察血清炎症标志物、脾脏病理特征、肾损伤和血管功能。结果表明,黄连碱降低了SLE小鼠血清自身抗体和血清炎症标志物的水平,改善了脾脏的病理特征,同时改善了肾损伤,减少了肾脏的炎症反应,降低了血压,并改善了血管内皮功能。蛋白质免疫印迹分析显示,抑制NF-κB和Rho/ROCK信号通路以及下游信号分子的激活可能是黄连碱发挥作用的潜在机制。我们的研究结果表明,黄连碱治疗可能是预防SLE以及改善相关肾脏和心血管并发症的一种策略。