In recent years, kidney damage caused by ingestion of Chinese medicinal herbs containing Aristolochic acid (AA) has attracted extensive attention. However, whether the nephrotoxicity of AA is related to NLRP3 inflammasome has not been reported. Hirsutella sinensis (HS) has a certain therapeutic effect on aristolochic acid nephropathy (AAN) and is related to NLRP3 inflammasome. Therefore, this study explores whether HS plays a role in renal injury induced by AA through NLRP3 inflammasome pathway. AA-stimulated renal tubular epithelial cells showed that AA could promote the expression of NLRP3, ASC, and α-SMA, increase the secretion and expression of caspase-1, IL-1β, and IL-18, and inhibit the expression of E-cadherin in a dose- and time-dependent manner. When NLRP3 was down-regulated, the expression of α-SMA and E-cadherin did not change significantly, but significantly blocked the regulation of α-SMA and E-cadherin expression by AA. When AA and HS were added to renal tubular epithelial cells at the same time, the effects of AA on the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18, and α-SMA gradually decreased to the level of control group with the increase of HS dosage. At the same time, HS can reduce the transdifferentiation of renal tubular epithelial cells by inhibiting the activation of NLRP3 inflammasome. These findings will provide important pharmacological references for the treatment of AAN and the clinical application of HS.

中文翻译：

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中华Hirsutella sinensis抑制NLRP3炎性体激活，从而阻止马兜铃酸诱导的肾小管上皮细胞转分化。

近年来，由于摄入含有马兜铃酸（AA）的中药引起的肾脏损害引起了广泛关注。然而，尚未报道AA的肾毒性是否与NLRP3炎性体有关。中华（HS）对马兜铃酸肾病（AAN）有一定的治疗作用，并且与NLRP3炎性体有关。因此，本研究探讨了HS是否在通过NLRP3炎性体途径由AA引起的肾损伤中起作用。AA刺激的肾小管上皮细胞显示AA可以促进NLRP3，ASC和α-SMA的表达，增加caspase-1，IL-1β和IL-18的分泌和表达，并抑制E-钙黏着蛋白呈剂量和时间依赖性。当NLRP3被下调时，α-SMA和E-钙粘蛋白的表达没有明显改变，但是显着阻断了AA对α-SMA和E-钙粘蛋白表达的调节。将AA和HS同时添加到肾小管上皮细胞中时，AA对NLRP3，ASC，caspase-1，IL-1β，IL-18，随着HS剂量的增加，α-SMA逐渐降低至对照组。同时，HS可以通过抑制NLRP3炎性小体的激活来减少肾小管上皮细胞的转分化。这些发现将为AAN的治疗和HS的临床应用提供重要的药理参考。