首页|水苏碱调节HIF-1α/NLRP3信号通路对缺氧/复氧诱导的心肌细胞焦亡的影响

水苏碱调节HIF-1α/NLRP3信号通路对缺氧/复氧诱导的心肌细胞焦亡的影响

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目的 研究水苏碱(stachydrine，STA)对缺氧/复氧(hypoxia/reoxygenation，H/R)诱导的心肌细胞焦亡模型缺氧诱导因子-1α(hypoxia inducible factor-1α，HIF-1α)/NOD 样受体热蛋白结构域相关蛋白 3(NOD-like receptor thermal protein domain associ-ated protein 3，NLRP3)信号通路的影响。方法 将心肌细胞H9C2细胞分为对照组(Control组)、模型组(H/R组)、H/R+低浓度STA 组(H/R+STA-L 组，5 μmol·L-1)、H/R+中浓度 STA 组(H/R+STA-M 组，10 μmol·L-1)、H/R+高浓度 STA 组(H/R+STA-H 组，20 μmol·L-1)、H/R+高浓度 STA(20 μmol·L-1)+HIF-1α 激活剂组[H/R+STA-H+二甲基草酰甘氨酸(DMOG)组，20 μmol·L-1的STA+10 μmol·L-1 DMOG]。细胞计数试剂盒8(CCK-8)检测H9C2细胞活性;流式细胞仪检测H9C2细胞焦亡;酶联免疫吸附法(ELISA)检测细胞白细胞介素-1β(IL-1β)、白细胞介素-18(1L-18)、乳酸脱氢酶(LDH)水平。蛋白质印迹(Western blot)检测IL-1β、IL-18、半胱天冬酶-1(Caspase-1)、HIF-1α、NLRP3表达。结果 与Control组比较，H/R组细胞存活率降低(P＜0。05)，Caspase-1 阳性表达率、IL-1β、IL-18、LDH 水平、Caspase-1、IL-1β、IL-18、HIF-1α、NLRP3 蛋白表达升高(P＜0。05);与H/R组比较，H/R+STA-L组、H/R+STA-M组、H/R+STA-H组细胞存活率增加，Caspase-1阳性表达率、IL-1β、IL-18、LDH水平、Caspase-1、IL-1β、IL-18、HIF-1α、NLRP3 蛋白表达降低(P＜0。05);与 H/R+STA-H 组比较，H/R+STA-H+DMOG 组的细胞存活率显著降低(P＜0。05)，Caspase-1 阳性表达率、IL-1β、IL-18、LDH 水平、Caspase-1、IL-1β、IL-18、HIF-1α、NLRP3 蛋白表达显著升高(P＜0。05)。结论 STA能够抑制H/R诱导的心肌细胞焦亡，其机制可能与HIF-1α/NLRP3信号通路相关。
Effect of Stachydrine on Hypoxia/Reoxygenation Induced Cardiomyocyte Pyroptosis by Regulating the HIF-1α/NLRP3 Signaling Pathway
OBJECTIVE To investigate the effect of stachydrine(STA)on hypoxia inducible factor-1α(HIF-1α)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in hypoxia/reoxygenation(H/R)induced cardiomyo-cyte pyroptosis model.METHODS H9C2 cardiomyocytes were separated into control group(Control group),model group(H/R group),H/R+low concentration STA group(H/R+STA-L group,5 μmol·L-1),H/R+medium concentration STA group(H/R+STA-M group,10 μmol·L-1),H/R+high concentration STA group(H/R+STA-H group,20 μmol·L-1),H/R+high concentration STA(20 μmol·L-1)+HIF-1α activator group[H/R+STA-H+dimethyloxaloglycine(DMOG)group,20 μmol·L-1 STA+10 μmol·L-1 DMOG].H9C2 cell viability was tested by cell counting kit-8(CCK-8)assay.H9C2 cell apoptosis was meas-ured by flow cytometry.The levels of IL-1β,IL-18,and LDH in cells were detected by enzyme linked immunosorbent assay(ELISA).The expression levels of IL-1β,IL-18,Caspase-1,HIF-1α,and NLRP3 were quantified using Western blot.RESULTS Compared with the control group,the cell survival rate of the H/R group decreased(P＜0.05),the positive expression rate of Caspase-1,levels of IL-1β,IL-18,LDH,and protein expression of Caspase-1,IL-1β,IL-18,HIF-1α,and NLRP3 increased(P＜0.05).Compared with the H/R group,the cell survival rates of the H/R+STA-L group,H/R+STA-M group and H/R+STA-H group increased,the positive expression rate of Caspase-1,levels of IL-1β,IL-18,LDH,and protein expression of Caspase-1,IL-1β,IL-18,HIF-1α,and NLRP3 reduced(P＜0.05).Compared with the H/R+STA-H group,the cell survival rate of the H/R+STA-H+DMOG group obvi-ously reduced(P＜0.05),the positive expression rate of Caspase-1,levels of IL-1β,IL-18,LDH,and protein expression of Caspase-1,IL-1β,IL-18,HIF-1α,and NLRP3 obviously increased(P＜0.05).CONCLUSION STA can inhibit H/R induced cardiomyocyte pyroptosis,and its mechanism may be related to the HIF-1α/NLRP3 signaling pathway.

stachydrinehypoxia inducible factor-1α/NOD-like receptor thermal protein domain associated protein 3hypoxia/reoxygenationcardiomyocytecell pyroptosis

李效丽、王涛、董传芳、许亚男、张晓苹

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山东省立第三医院特需保健科,济南 250031

山东省立第三医院老年病科,济南 250031

解放军第九六零医院全科医学科,济南 250031

水苏碱 缺氧诱导因子-1α/NOD样受体热蛋白结构域相关蛋白3 缺氧/复氧 心肌细胞 细胞焦亡

2024

10.11669/cpj.2024.24.006

中国药学杂志
中国药学会

中国药学杂志

CSTPCD北大核心
影响因子：0.957
ISSN：1001-2494
年,卷(期)：2024.59(24)