Inflammatory response is important for the development and progression of diabetic nephropathy (DN). Artesunate (ART), an antimalarial drug, possesses anti-inflammatory effect and exhibits protective effect on chronic kidney diseases. However, the effect of ART on DN is unknown. The aim of the present study was to evaluate the effect and the molecular mechanism of ART on DN in an in vitro model. The rat mesangial cell line, HBZY-1, was induced by high glucose (HG; 30 mM d-glucose) in the presence or absence of ART (15 and 30 μg/ml) and incubated for 24 h. We found that HG induced the proliferation of HBZY-1 cells, while treatment with ART inhibited the cell proliferation. Treatment with ART inhibited HG-induced inflammatory cytokines production and expression of extracellular matrix (ECM). Besides, HG induced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inhibited the superoxide dismutase (SOD) activity of HBZY-1 cells, and the effects were attenuated by ART treatment. ART decreased HG-induced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), nuclear factor κB (NF-κB) p-p65, and nod-like receptor protein 3 (NLRP3). Inhibition of the TLR4/NF-κB pathway suppressed NLRP3 inflammasome in HBZY-1 cells. In conclusion, ART exhibited protective effect on HG-induced HBZY-1 cells by inhibiting the inflammatory response, oxidative stress and ECM accumulation. The TLR4/NF-κB/NLRP3 inflammasome pathway was involved in the protective effect of ART. The results suggested that ART might be a potential therapy agent for the DN treatment.

炎症反应对糖尿病肾病（DN）的发展和进展很重要。青蒿琥酯（ART）是一种抗疟疾药物，具有抗炎作用，并对慢性肾脏疾病具有保护作用。但是，ART对DN的影响尚不清楚。本研究的目的是在体外模型中评估ART对DN的作用及其分子机制。高糖（HG; 30 mM d-葡萄糖）在存在或不存在ART的情况下（15和30μg/ ml）孵育24小时。我们发现，HG诱导了HBZY-1细胞的增殖，而ART治疗则抑制了细胞的增殖。ART的治疗抑制了HG诱导的炎症细胞因子的产生和细胞外基质（ECM）的表达。此外，HG诱导了活性氧（ROS）和丙二醛（MDA）的水平，并抑制了HBZY-1细胞的超氧化物歧化酶（SOD）活性，ART处理后其作用减弱了。ART降低了HG诱导的Toll样受体4（TLR4），髓样分化初级反应基因88（MyD88），核因子κB（NF-κB）p-p65和nod样受体蛋白3（NLRP3）的表达水平。 。抑制TLR4 /NF-κB通路可抑制HBZY-1细胞中的NLRP3炎性小体。综上所述，ART通过抑制炎症反应，氧化应激和ECM积累，对HG诱导的HBZY-1细胞具有保护作用。TLR4 /NF-κB/ NLRP3炎性体途径参与了ART的保护作用。结果表明，ART可能是DN治疗的潜在治疗剂。