黄芪甲苷通过调节水液代谢改善辐射诱导心肌细胞水肿的研究  

AstragalosideⅣameliorates irradiation-induced cardiomyocyte edema by modulating fluid metabolism

作　　者：张尚祖 张利英[1,2] 李启杨 陈琰 李洋洋 刘永琦 ZHANG Shang-zu;ZHANG Li-ying;LI Qi-yang;CHEN Yan;LI Yang-yang;LIU Yong-qi(Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities,Key Laboratory of Dunhuang Medicine and Transformation Ministry of Education,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,Gansu Province,China;Gansu Institute of Cardiovascular Diseases,Lanzhou 730050,Gansu Province,China)

机构地区：[1]甘肃中医药大学,甘肃省高校重大疾病分子医学与中医药防治研究重点实验室,敦煌医学与转化教育部重点实验室,甘肃兰州730000 [2]甘肃省心血管病研究所,甘肃兰州730050

出　　处：《中国临床药理学杂志》2024年第13期1874-1877,共4页The Chinese Journal of Clinical Pharmacology

基　　金：中国博士后科学基金资助项目(2021M693794);甘肃省“双一流”科研重点基金资助项目(GSSYLXM-05);敦煌医学与转化教育部重点实验室开放课题资助项目(DHYX23-09)。

摘　　要：目的研究黄芪甲苷(AS-Ⅳ)改善辐射诱导的心肌细胞水肿的有效性及其分子机制。方法将AC16细胞分为空白组、模型组、AS-Ⅳ辐射前给药组(Q组)、辐射后给药组(H组)和前+后给药组(Q+H组)。Q组和Q+H组用40 mol·L^(-1)的AS-Ⅳ含药培养基,其他各组用正常培养基,培养24 h后,除空白组外,其余各组给予6 Gy X射线辐射建立心肌细胞水肿模型,并将Q组更换为正常培养基,H组更换为40 mol·L^(-1)的AS-Ⅳ含药培养基,培养24 h。用钙黄绿素AM染色法观察细胞的水肿情况,用蛋白质印迹法检测水液代谢关键蛋白的表达情况,用Annexin-V/PI流式凋亡检测法检测细胞的凋亡情况。结果空白组、模型组、Q组、H组和Q+H组的细胞水肿面积分别为690.77±199.55、1184.47±307.36、713.65±152.48、809.72±262.85和897.61±213.66,缺氧诱导因子(HIF)-1α蛋白相对表达水平分别为0.94±0.02、1.35±0.03、0.91±0.03、0.69±0.02和0.86±0.03,水通道蛋白4(AQP4)蛋白相对表达水平分别为0.66±0.03、1.07±0.04、0.67±0.02、0.56±0.03和0.56±0.02,凋亡率分别为(3.90±0.76)%、(16.58±0.63)%、(12.91±0.51)%、(14.05±0.22)%和(12.13±0.38)%。空白组、Q组、H组和Q+H组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论AS-Ⅳ可以通过抑制辐射后AC16细胞HIF-1α/AQP4轴的异常激活,调节水液代谢,改善辐射诱导的心肌细胞水肿,减少细胞凋亡。Objective To investigate the effectiveness of astragalosideⅣ(AS-Ⅳ)in ameliorating radiation-induced cardiomyocyte edema and its molecular mechanism.Methods The AC 16 cells were divided into blank group,model group,AS-Ⅳpre-irradiation administration group(Q group),post-irradiation administration group(H group)and pre-post-irradiation administration group(Q+H group).H group was incubated with 40 mol·L^(-1)AS-Ⅳdrug-containing medium,and the other groups were incubated with normal medium for 24 h.After 24 h of incubation,6 Gy X-ray irradiation was given to establish the cardiomyocyte edema model in all groups except the blank group,and group Q was replaced with normal medium,and group H was replaced with 40 mol·L^(-1)AS-Ⅳdrug-containing medium for 24 h of incubation.Calcein AM staining was used to observe the edema of AC 16cells,Western blot method was used to detect the expression of key proteins of aqueous fluid metabolism,and Annexin-Ⅴ/PI flow apoptosis assay was used to detect apoptosis of AC 16 cells.Results The area of cellular edema in blank,model,Q,H,and Q+H groups were 690.77±199.55,1184.47±307.36,713.65±152.48,809.72±262.85and 897.61±213.66;the relative expression levels of hypoxia inducible factor(HIF)-1αprotein were 0.94±0.02,1.35±0.03,0.91±0.03,0.69±0.02 and 0.86±0.03;the relative expression levels of aquaporin 4(AQP4)protein were 0.66±0.03,1.07±0.04,0.67±0.02,0.56±0.03 and 0.56±0.02;the apoptosis rates were(3.90±0.76)%,(16.58±0.63)%,(12.91±0.51)%,(14.05±0.22)%and(12.13±0.38)%,respectively.Statistically significant differences were found between the above indicators in the blank,Q,H and Q+H groups when compared to the model group(all P<0.05).Conclusion AS-Ⅳcan regulate water-liquid metabolism,ameliorate radiation-induced cardiomyocyte edema,and attenuate apoptosis by inhibiting the abnormal activation of the HIF-1α/AQP4 axis in irradiated AC 16 cells.

关 键 词：黄芪甲苷 辐射 心肌水肿 缺氧诱导因子-1Α 水通道蛋白4 

分 类 号：R28[医药卫生—中药学]