首页|芪地糖肾方调控NLRP3/Caspase-1/GSDMD通路介导高糖刺激肾小球内皮细胞焦亡的研究

芪地糖肾方调控NLRP3/Caspase-1/GSDMD通路介导高糖刺激肾小球内皮细胞焦亡的研究

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目的 探究芪地糖肾方通过NOD样受体家族热蛋白结构域相关蛋白3/半胱氨酸天冬氨酸蛋白酶-1/消皮素D蛋白(NLRP3/Caspase-1/GSDMD)通路介导高糖刺激的肾小球内皮细胞焦亡的作用。方法 将肾小球内皮细胞分为正常组、高糖组、芪地糖肾方组,分别予完全培养基、30 mmol/L高糖培养基、30 mmol/L高糖培养基+芪地糖肾方100 μg/mL培养48 h,采用细胞免疫荧光染色法观察细胞中NLRP3 表达情况及细胞骨架情况,采用Western blot法检测细胞中NOD样受体热蛋白结构域相关蛋白3(NLRP3)、半胱氨酸天冬氨酸蛋白酶1(Caspase-1)、消皮素D蛋白(GSDMD)、凋亡相关斑点样蛋白(ASC)、白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)表达情况。结果 与正常组比较,高糖组细胞中NLRP3、Caspase-1、GSDMD、ASC、IL-18、IL-1β蛋白相对表达量均明显升高(P均<0。05),NLRP3 荧光表达信号增强,细胞骨架损伤明显;与高糖组比较,芪地糖肾方组NLRP3、Caspase-1、GSDMD、ASC、IL-18、IL-1β蛋白相对表达量均明显降低(P均<0。05),NLRP3 荧光表达信号减弱,细胞骨架损伤状态改善。结论 芪地糖肾方可通过抑制NLRP3/Caspase-1/GSDMD焦亡相关通路激活改善高糖诱导的肾小球内皮细胞损伤。
Qi Di Tang Shen decoction mediates high glucose-stimulated glomerular endothelial cells'pyroptosis via regulating NLRP3/Caspase1/GSDMD pathway
Objective It is to investigate the effect of Qi Di Tang Shen decoction on high glucose-stimulated glomerular endothelial cells(mGECs)via Nod-like receptor protein 3/cystein-asparate protease-1/gasdermin D(NLRP3/Caspase1/GSDMD)pathway.Methods The mGECs were divided into three groups,named as normal group,high glucose group and Qi Di Tang Shen decoction group,which were respectively cultured in complete medium,30 mmol/L high-glucose medi-um,30 mmol/L high-glucose medium +100 μg/mL Qi Di Tang Shen decoction for 48 h.The expression of NLRP3 in cells and cytoskeleton were observed by cellular immunofluorescence staining,the expressions of NLRP3,Caspase1,apoptosis-associated spot-like protein(ASC),GSDMD,interleukin-1β(IL-1β)and interleukin-18(IL-18)in mGECs were detec-ted by cellular immunofluorescence staining.Results Compared with the normal group,the relative expressions of NLRP3,Caspase1,GSDMD,ASC,IL-18 and IL-1β in mGECs of the high glucose group were significantly increased(all P<0.05),the fluorescent expression of NLRP3 was enhanced,and the cytoskeleton damage was obvious.Compared with the high glucose group,the relative expressions of NLRP3,Caspase1,GSDMD,ASC,IL-18 and IL-1β in Qi Di Tang Shen decoction group were significantly down-regulated(all P<0.05),and the fluorescent expression of NLRP3 was decreased and the cytoskeletal damage was improved.Conclusion Qi Di Tang Shen decoction can improve the high-glucose induced injury of glomerular endothelial cells by inhibiting the activation of NLRP3/Caspase1/GSDMD pathway.

diabetic kidney diseaseglomerular endothelial cellsQi Di Tang Shen decoctionpyroptosisNod-like receptor protein 3cystein-asparate protease-1gasdermin D

史扬、董昭熙、周盈、谢惠迪、郭燕、宿家铭、郑毅成、柳红芳

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北京中医药大学东直门医院,北京 100700

北京市普仁医院,北京 100062

解放军总医院第一医学中心肾脏病全国重点实验室,北京 100853

糖尿病肾脏病 肾小球内皮细胞 芪地糖肾方 焦亡 NOD样受体家族热蛋白结构域相关蛋白3 半胱氨酸天冬氨酸蛋白酶-1 消皮素D蛋白

北京市自然科学基金资助项目国家自然科学基金资助项目国家中医药管理局国家中医临床研究基地业务建设科研专项课题

721218082004297JDZX2015305

2024

现代中西医结合杂志
中国中西医结合学会河北分会,中华中医药学会

现代中西医结合杂志

CSTPCD
影响因子:1.775
ISSN:1008-8849
年,卷(期):2024.33(1)
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