【摘要】 目的 研究羟基红花黄色素A（HSYA）对慢性高原红细胞增多症大鼠的调控作用。方法 在低压低氧舱中模拟海拔5 000 m缺氧30 d,建立慢性高原病模型。将SD大鼠随机分为对照组、模型组、阳性对照组及实验组。实验组设立低、中、高剂量实验组并腹腔注射HSYA(15、30、60 mg·kg^-1),阳性对照组灌胃乙酰唑胺(ACZ;50 mg·kg^-1),对照组及模型组均灌胃等体积0.9%NaCl,每日1次，连续给药15 d并持续保持低压低氧暴露。用全自动血液分析仪测定血细胞比容（HCT）、红细胞计数（RBC）和血红蛋白（HGB）水平，用蛋白质印迹法检测缺氧诱导因子1α（HIF-1α）、缺氧诱导因子2α（HIF-2α）、促红细胞生成素（EPO）等蛋白的表达水平。结果 对照组、模型组、阳性对照组和高、中、低剂量实验组HCT分别为（37.65±4.05）%、（70.03±2.27）%、（54.23±3.72）%、（65.00±2.42）%、（65.90±2.19）%和（64.27±3.05）%,RBC分别为（5.58±0.44）、（9.02±0.43）、（7.31±0.37）、（8.05±0.63）、（8.61±0.47）和（8.16±0.34）10¹²·L^-1,HGB含量分别为（130.46±11.22）、（237.69±12.55）、（185.70±9.02）、（197.53±9.68）、（216.37±9.15）和（188.48±8.37）g·L^-1,HIF-1α蛋白相对表达水平分别为0.44±0.11、0.45±0.08、1.03±0.01、0.67±0.11、0.50±0.10和0.73±0.16,HIF-2α蛋白相对表达水平分别为0.51±0.08、0.90±0.11、0.43±0.06、0.55±0.08、0.78±0.12和0.79±0.03,EPO蛋白相对表达水平分别为0.38±0.02、0.89±0.06、0.47±0.02、0.72±0.07、0.87±0.13和0.78±0.05。高、中、低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<0.05）。结论 HSYA可差异性影响HIF-1α以及HIF-2α的表达，调控下游造血和血管生成相关通路，从而改善慢性高原红细胞增多症。更多还原

【Abstract】 Objective To investigate the regulatory effect of hydroxysafflor yellow A（HSYA） on chronic high altitude polycythemia rats.Methods A chronic high altitude disease model was established by simulating at an altitude of 5 000 m in a low-pressure and low oxygen chamber for 30 days.SD rats were randomly divided into control group,model group,positive control group,and experimental group.The experimental group was divided into low,medium,and high dose groups with HSYA(15,30,and 60 mg·kg^-1) was intraperitoneally injected,the positive control group was orally administered with acetazolamide(ACZ;50 mg·kg^-1),and the control group and model group were administered with equal volumes of physiological saline by gavage,once a day for 15 consecutive days while maintaining low-pressure hypoxia exposure.The hematocrit（HCT）,red blood cell count（RBC）,hemoglobin（HGB） were measured by automated hematology analyzer,and the expression levels of hypoxia inducible factor 1 alpha（HIF-1α）,hypoxia inducible factor 2 alpha（HIF-2α）,erythropoietin（EPO） were detected by Western blot.Results For control group,model group,positive control group,experimental-H,-M,-L groups,the HCT were（37.65±4.05）%,（70.03±2.27）%,（54.23±3.72）%,（65.00±2.42）%,（65.90±2.19）% and（64.27±3.05）%,respectively;the RBC were（5.58±0.44）,（9.02±0.43）,（7.31±0.37）,（8.05±0.63）,（8.61±0.47） and（8.16±0.34） 10¹²·L^-1,respectively;the HGB contents were（130.46±11.22）,（237.69±12.55）,（185.70±9.02）,（197.53±9.68）,（216.37±9.15） and（188.44±8.37） g·L^-1,respectively;the relative expression levels of HIF-1α protein were 0.44±0.11,0.45±0.08,1.03±0.01,0.67±0.11,0.50±0.10 and 0.73±0.16,respectively;the relative levels of HIF-2α protein were 0.51±0.08,0.90±0.11,0.43±0.06,0.55±0.08,0.78±0.12 and 0.79±0.03,respectively;the relative levels of EPO protein were 0.38±0.02,0.89±0.06,0.47±0.02,0.72±0.07,0.87±0.13 and 0.78±0.05,respectively.The above indicators of the experimental-H,-M,-L groups were compared with the model group,and the differences were statistically significant（all P <0.05）.Conclusion HSYA can differentially affect the expression of HIF-1αand HIF-2α,regulate downstream hematopoietic and angiogenesis related pathways,and improve chronic high altitude polycythemia.更多还原