文献类型：期刊文献

中文题名：武威汉简“瘀方”对高血压肾损伤大鼠HIF-1α/VEGF/Notch1通路的影响

英文题名：Effects of Wu Wei Han bamboo slips"Yufang"on HIF-1α/VEGF/Notch1 pathway in hypertensive kidney injury rats

作者：马睿玲[1,2];吕红英[1];侯明双[1];王怡园[1,2];寇雨顺[1];沈路凡[1];王鸿[1];张玲娜[1];伊琳[1,2]

第一作者：马睿玲

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730000;[2]甘肃省中医药防治慢性疾病重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学中西医结合学院

年份：2025

卷号：41

期号：11

起止页码：1575

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(82160842);甘肃省自然科学基金资助项目(24JRRA1019);甘肃省联合科研基金(一般项目)资助项目(23JRRA1521);甘肃省教育厅高校教师创新基金资助项目(2023A-083)。

语种：中文

中文关键词：武威汉简“瘀方”;缺氧诱导因子-1α;血管内皮生长因子;跨膜受体蛋白1;肾损伤

外文关键词：Wu Wei Han bamboo slips"Yufang";hypoxia inducible factor-lα;vascular endothelial growth factor;transmembrane receptor protein 1;kidney injury

摘要：目的探索武威汉简“瘀方”对自发性高血压大鼠肾损伤的影响,及其作用机制。方法分析GEO数据库中高血压肾病数据集GSE37460中正常肾组织与高血压肾病肾组织的差异基因,探讨高血压肾损伤机制。将自发性高血压大鼠(SHR)随机分为模型组(等体积蒸馏水)、对照组(7.59 mg·kg^(-1)缬沙坦)和低、中、高剂量实验组(7.15、14.29、28.58 g·kg^(-1)武威汉简“瘀方”颗粒剂),每组10只;另取Wistar-Kyoto(WKY)大鼠设为正常组(等体积蒸馏水)。6组大鼠每天灌胃1次,连续给药8周。用酶联免疫吸附试验法检测大鼠尿中微量白蛋白(mALB)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)含量和血清中血栓素(TXB2)、6-酮-前列腺素F1α(6-keto PGF1α)含量,用蛋白质印迹法检测大鼠肾组织中缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)和跨膜受体蛋白1(Notch1)蛋白的表达水平。结果在数据集GSE37460中,共发现155个差异基因,其中,上调94个、下调61个,通路富集涉及HIF-1α/VEGF/Notch1等通路。正常组、模型组、对照组和高剂量实验组的尿mALB含量分别为(60.83±3.81)、(159.60±20.65)、(70.45±3.97)和(79.72±9.01)μg·L^(-1),尿NAG含量分别为(34.37±6.92)、(91.30±9.05)、(44.65±10.09)和(54.79±2.87)ng·L^(-1),血清TXB2含量分别为(78.58±3.78)、(107.80±5.16)、(80.92±4.02)和(85.65±2.17)pg·mL^(-1),血清6-keto PGF1α含量分别为(121.50±3.45)、(85.05±2.92)、(108.30±2.96)和(101.90±3.08)pg·mL^(-1),HIF-1α蛋白相对表达水平分别为0.56±0.03、1.25±0.02、0.77±0.01和0.83±0.02,VEGF蛋白相对表达水平分别为0.24±0.02、1.24±0.03、0.81±0.04和0.95±0.02,Notch1蛋白相对表达水平分别为0.33±0.03、1.02±0.01、0.50±0.04和0.68±0.01,对照组和高剂量实验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<0.01)。结论武威汉简“瘀方”可以改善高血压肾损伤,减轻肾纤维化,其机制可能与抑制HIF-1α/VEGF/Notch1信号通路有关。
Objective To explore the effects of Wu Wei Han bamboo slips"Yufang"on kidney injury in spontaneously hypertensive rats and its mechanism of action.Methods To analyze the differential genes between normal kidney tissues and hypertensive kidney tissues in GSE37460,a hypertensive kidney disease dataset in GEO database,and to explore the mechanism of hypertensive kidney injury;Spontaneously hypertensive rats(SHR)were randomly divided into model group(equal volume of distilled water),control group(7.59 mg·kg^(-1)valsartan)and experimental-L,-M,-H groups(7.15,14.29,28.58 g·kg^(-1)"Yufang"granules),with 10 rats in each group;additionally,Wistar-Kyoto(WKY)rats were taken as a normal group(equal volume of distilled water).Six groups were gavaged once a day for 8 consecutive weeks.The levels of urinary microalbumin(mAlb),N-acetyl-β-D-glucosaminidase(NAG)and serum thromboxane(TXB2),6-keto-prostaglandin F1α(6-keto PGF1α)were detected by enzyme linked immunosorbent assay.Western blot was used to detect the expression levels of hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF)and transmembrane receptor protein 1(Notch1)in rat kidney.Results The data set GSE37460 contained 155 differential genes,94 of which were up-regulated and 61 were down regulated and pathway enrichment involves pathways such as HIF-1α/VEGF/Notch1.The urinary mAlb levels of normal,model,control and experimental-H groups were(60.83±3.81),(159.60±20.65),(70.45±3.97)and(79.72±9.01)μg·L^(-1),respectively;the urinary NAG levels were(34.37±6.92),(91.30±9.05),(44.65±10.09)and(54.79±2.87)ng·L^(-1),respectively;the contents of TXB2 in serum were(78.58±3.78),(107.80±5.16),(80.92±4.02)and(85.65±2.17)pg·mL^(-1),respectively;the serum 6-keto PGF1αlevels were(121.50±3.45),(85.05±2.92),(108.30±2.96),(101.90±3.08)pg·mL^(-1),respectively;the relative expression levels of HIF-1αprotein in rat kidney were 0.56±0.03,1.25±0.02,0.77±0.01 and 0.83±0.02,respectively;the relative expression levels of VEGF protein were 0.24±0.02,1.24±0.03,0.81±0.04 and 0.95±0.02,respectively;the relative expression levels of Notch1 protein were 0.33±0.03,1.02±0.01,0.50±0.04 and 0.68±0.01,respectively;there were significant differences in the above indexes between the control and experimental-H groups and the model group(all P<0.05).Conclusion The Wuwei Han bamboo slips"Yufang"can improve hypertension-related kidney damage and reduce kidney fibrosis,and its mechanism may be related to the inhibition of the HIF-1α/VEGF/Notch1 signaling pathway.