基于内质网应激调控NLRP3炎症小体活化途径探讨丹酚酸B对造影剂肾病中肾小管损伤的保护作用及机制

造影剂肾病是医源性急性肾功能损伤的第三大主因，目前在临床上对造影剂肾病的防治措施仍十分有限。中医认为造影剂肾病主要表现为毒、淤和虚的特点，中药治疗主要采用清热解毒、活血化瘀等方法；现代医学研究认为其发病机制与肾小管损伤密切相关。我们的前期实验结果显示，造影剂可诱导肾小管上皮细胞损伤，机制可能与Klotho蛋白表达水平降低、内质网应激及NLRP3炎症小体的激活有关。活血化瘀的经典中药丹参的主要活性成分——丹酚酸B具有对抗造影剂诱导的肾小管上皮细胞损伤的作用，但其保护作用的机制仍然不清。而既往的研究报道Klotho具有抑制内质网应激的作用，内质网应激又可以调控NLRP3炎症小体的激活。因此，以内质网应激调控NLRP3炎症小体活化途径作为切入点，在整体、细胞、分子三个水平来阐述丹酚酸B对造影剂肾病的防治机制，不仅可以丰富丹酚酸B“活血化瘀”的物效内涵还有助于开发造影剂肾病的有效防治药物。

Contrast-induced nephropathy (CIN) is the third leading cause of iatrogenic acute renal dysfunction. Clinical prevention and treatment measures about contrast nephropathy are still very limited at present. Traditional Chinese medicine believes that CIN is mainly characterized by toxicity, stasis and asthenia, and Chinese medicine mainly via heat-clearing and detoxifying, activating blood circulation and dissipat blood stasis to achieve the therapeutic effect. Modern medical researches show that its pathogenesis is closely related to renal tubular injury. Our previous experimental results show that contrast medium can induce renal tubular epithelial cell damage, and the mechanism may be related to the reduced level of Klotho protein expression, endoplasmic reticulum stress and the activation of NLRP3 inflammatory body. Salvia miltiorrhiza is a classic Chinese medicine to activating blood circulation and dissipat blood stasis. In addition, we found that salvianolic acid B, the main active ingredient of Salvia miltiorrhiza, has an anti-contrast-induced damage efficacy in renal tubular epithelial cells, however, its protective mechanism is still unclear. Previous studies have reported that Klotho has the effect of inhibiting endoplasmic reticulum stress, which can also regulate the activation of NLRP3 inflammatory body. Therefore, taking endoplasmic reticulum stress to regulate the activation pathway of NLRP3 inflammasome as an entry point to expound the prevention and treatment mechanism of salvianolic acid B about CIN on the whole, cellular and molecular levels, which can not only enrich the efficacy of salvianolic acid B, but also develop the effective drugs of contrast agent nephropathy.