HIF-1α/KDM3A信号通路在肾康丸改善缺氧高糖诱导的HUVECs炎性损伤中的作用  

Role of HIF-1α/KDM3A Signaling Pathway in the Improvement of Hypoxia and High Glucose-induced Inflammatory Injury in HUVECs by Shenkang Pills

作　　者：钟巧慧 王少婷 左安娜 林浩裕 谢家润 江伟强[1] 夏金金 王明[1,2] ZHONG Qiaohui;WANG Shaoting;ZUO Anna(School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515)

机构地区：[1]南方医科大学珠江医院,广州510280 [2]南方医科大学中医药学院,广州510515

出　　处：《中国中西医结合肾病杂志》2022年第11期949-956,I0001,共9页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家自然科学基金资助项目(No.82074207);广东省自然科学基金资助项目(No.2021A1515011502);广东省中医药局科研项目(No.20223007);大学生创新创业训练计划项目(No.S202112121157)。

摘　　要：目的:探讨HIF-1α/KDM3A信号通路在肾康丸改善缺氧高糖诱导的HUVECs炎性损伤中的作用。方法:利用STZ诱导单侧肾切除DN小鼠作为体内实验模型,缺氧高糖条件下诱导的人脐静脉内皮细胞HUVECs作为体外模型,给予肾康丸干预,采用荧光定量PCR、Western blot和ELISA检测IL-6、IL-8、ICAM-1、MCP-1等基因和蛋白表达水平及HIF-1α、KDM3A表达水平。结果:体内实验中,与正常对照组比较,模型组小鼠炎症因子表达均显著升高(P<0.01,P<0.05),与模型组比较,肾康丸中、高剂量组小鼠IL-1β、HIF-1α、MCP-1、ICAM-1、HIF-1α、KDM3A基因表达水平明显降低(P<0.01,P<0.05),差异具有统计学意义。体外实验中,慢性缺氧能够进一步增加高糖状态下HUVECs炎症因子表达水平,同时HIF-1α、KDM3A在缺氧高糖下表达水平显著上升,HIF-1α抑制剂能够降低KDM3A以及炎症因子的表达,沉默KDM3A能够减弱HUVECs炎性损伤水平。结论:缺氧高糖显著增加HUVECs细胞炎症损伤,并增加HIF-1α、KDM3A表达;肾康丸可以通过调控HIF-1α/KDM3A信号通路减缓缺氧高糖下HUVECs炎性损伤水平。Objective:To investigate the role of HIF-1α/KDM3 A signaling pathway in the improvement of hypoxia-hyperglucose-induced inflammatory injury in HUVECs by Shenkang Pills.Methods:Using STZ-induced unilateral nephrectomized DN mice as an in vivo experimental model and human umbilical vein endothelial cells HUVECs induced under hypoxic high-glucose conditions as an in vitro model,we administered Shenkang Pills to intervene and detected the gene and protein expression levels of IL-6,IL-8,ICAM-1,MCP-1,etc.and HIF-1α,KDM3 A expression levels.Results:In the in vivo experiment,compared with the normal control group,the expression of inflammatory factors were significantly increased in the model group(P<0.01,P<0.05).The expression levels of IL-1β,MCP-1,ICAM-1,HIF-1αand KDM3 A genes were significantly decreased in the middle and high dose groups of Shenkang Pill compared with the model group(P<0.01,P<0.05),and the differences were statistically significant.In in vitro experiments,chronic hypoxia could further increase the expression levels of inflammatory factors in HUVECs under high glucose status,while the expression levels of HIF-1αand KDM3 A were significantly increased under hypoxia and high glucose.HIF-1αinhibitor could reduce KDM3 A expression and inflammatory factors,and silencing KDM3 A could attenuate the levels of inflammatory and oxidative stress damage in HUVECs.Conclusion:Hypoxic hyperglycemia significantly increased the inflammatory damage of HUVECs cells and increased the expression of HIF-1αand KDM3 A;Shen kang pill could slow down the level of inflammatory damage of HUVECs under hypoxic hyperglycemia by regulating the HIF-1α/KDM3 A signaling pathway.

关 键 词：肾康丸 糖尿病肾病 KDM3A 人脐静脉内皮细胞 

分 类 号：R285.5[医药卫生—中药学]