Clinical Drug Trial Institution, Affiliated Hospital of Chengdu University, Chengdu, 610081, Sichuan, People's Republic of China.
Department of Urology, Affiliated Hospital of Chengdu University, Chengdu, 610081, Sichuan, People's Republic of China.
Inflammation. 2020 Apr;43(2):433-440. doi: 10.1007/s10753-019-01106-x.
Pyroptosis, a new pro-inflammatory programmed cell death, is linked to atherosclerosis (AS). Our previous studies suggested that salidroside (SAL) can alleviate AS and exert anti-oxidative and anti-inflammatory properties. However, the effect of SAL on atherosclerosis-related pyroptosis has not been studied. Here, we investigated the effect of SAL on pyroptosis to explain the underlying mechanisms of SAL on atherosclerosis-related inflammation. We established an atherosclerosis mouse model via western diet (HFD) to explore the protective effect of SAL. According to our results, administration of SAL for 12 weeks markedly reduced the atherosclerotic plaque in aorta. Meanwhile, SAL also alleviated the pyroptosis, as evidenced by inhibiting caspase-1 activation, interleukin-1β (IL-1β) release, and TUNEL-positive staining, and decreasing the expression of Gasdermin D (GSDMD). Furthermore, SAL also decreased the activation of caspase-1 and inhibited the release of IL-1β induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in human umbilical vein endothelial cell (HUVECs). Our data indicate that SAL inhibit NLRP3-related pyroptosis, which might be the underlying mechanism of SAL anti-inflammatory in atherosclerosis.
细胞焦亡是一种新的促炎程序性细胞死亡方式，与动脉粥样硬化（AS）有关。我们之前的研究表明，红景天苷（SAL）可以减轻 AS 并发挥抗氧化和抗炎作用。然而，SAL 对动脉粥样硬化相关细胞焦亡的影响尚未研究。在这里，我们研究了 SAL 对细胞焦亡的影响，以解释 SAL 对动脉粥样硬化相关炎症的潜在机制。我们通过西方饮食（HFD）建立了动脉粥样硬化小鼠模型，以探索 SAL 的保护作用。根据我们的结果，SAL 给药 12 周可显著减少主动脉中的动脉粥样硬化斑块。同时，SAL 还减轻了细胞焦亡，表现为抑制半胱氨酸天冬氨酸蛋白酶-1（caspase-1）的激活、白细胞介素-1β（IL-1β）的释放和 TUNEL 阳性染色，并降低了 Gasdermin D（GSDMD）的表达。此外，SAL 还可降低 caspase-1 的激活，并抑制脂多糖（LPS）和三磷酸腺苷（ATP）诱导的人脐静脉内皮细胞（HUVECs）中 IL-1β的释放。我们的数据表明，SAL 抑制 NLRP3 相关的细胞焦亡，这可能是 SAL 在动脉粥样硬化中抗炎的潜在机制。
