基于Nrf2通路研究丹参酮ⅡA对自发性高血压大鼠血压及血管活性物质的影响  

Effects of TanshinoneⅡA on Spontaneous Hypertensive Rats and Vasoactive Substances Based on Nrf2 Pathway

作　　者：李文娣 孙娟[2] LI Wendi;SUN Juan(Hospital of PLA Joint Logistic Support Force,Changchun 130062,Jilin,China)

机构地区：[1]解放军联勤保障部队九六四医院,长春130062 [2]新疆医科大学第一附属医院心,乌鲁木齐830054

出　　处：《中西医结合心脑血管病杂志》2021年第7期1103-1107,1112,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：新疆维吾尔自治区自然科学基金(No.2019D01C174)。

摘　　要：目的探讨丹参酮ⅡA通过转录因子NF-E2相关因子2(Nrf2)通路对自发性高血压大鼠(SHR)的疗效及血管活性物质的影响。方法15只健康雄性Wistar-Kyoto(WKY)大鼠为空白对照组,60只雄性自发性高血压大鼠随机分为自发性高血压组、丹参酮ⅡA低剂量组(25 mg/kg)、丹参酮ⅡA高剂量组(50 mg/kg)和苯那普利组(10 mg/kg)。连续灌胃8周,在1周、5周、8周时测量各组大鼠收缩压情况;苏木精-伊红(HE)染色观察各组大鼠胸主动脉形态学;眼底观察各组大鼠视网膜动脉变化;酶联免疫吸附法(ELISA)测定各组大鼠血清中血管紧张素Ⅱ(AngⅡ)、内皮素(ET)、去甲肾上腺素(NE)和血栓素B_(2)(TXB_(2))的含量变化;免疫组化检测各组大鼠胸主动脉中AT1R的阳性表达;免疫印迹法(Western Blot)检测各组大鼠胸主动脉中Nrf2、血红素氧合酶1(HO-1)、依赖还原型辅酶/Ⅱ醌氧化还原酶Ⅰ(NQO1)蛋白表达水平。结果与自发性高血压组相比,丹参酮ⅡA低剂量组、丹参酮ⅡA高剂量和苯那普利组均能降低大鼠收缩压(P<0.05);丹参酮ⅡA低剂量组、丹参酮ⅡA高剂量和苯那普利组均能改善血管内皮损伤和提高血管弹性;与空白对照组比较,自发性高血压组大鼠视网膜动脉直径略窄,丹参酮ⅡA低剂量组、丹参酮ⅡA高剂量组和苯那普利组均能使大鼠视网膜动脉直径变宽;自发性高血压组大鼠血清中AngⅡ、ET、NE和TXB_(2)的含量均明显增加(均P<0.01),丹参酮ⅡA低剂量、丹参酮ⅡA高剂量和苯那普利能降低AngⅡ、ET、NE和TXB_(2)的含量(均P<0.05或P<0.01);AngⅡ的受体(ATIR)在自发性高血压大鼠胸主动脉中呈阳性表达,在丹参酮ⅡA低剂量组、丹参酮ⅡA高剂量组和苯那普利组中阳性表达降低;自发性高血压组大鼠胸主动脉中Nrf2、HO-1和NQO1的蛋白表达量降低(均P<0.01),丹参酮ⅡA低剂量、丹参酮ⅡA高剂量和苯那普利能提高大鼠胸主动脉中Nrf2、HO-1和NQO1的蛋白表�Objective To explore the effects of TanshinoneⅡA on spontaneous hypertensive rats(SHR)and vasoactive substances based on NF-E2 factor 2(Nrf2)pathway.Methods Fifteen male Wistar-Kyoto(WKY)rats were used as a blank control group,and 60 male SHRs were randomly divided into spontaneous hypertension group,low dose TanshinoneⅡA group(25 mg/kg),high dose TanshinoneⅡA group(50 mg/kg)and Benazepril group(10 mg/g).The rats were continuously gavaged for 8 weeks.At the first week,fifth week,and eighth week,systolic blood pressure of each group was measured.The morphology of thoracic aorta was observed by hematoxylin-eosin(HE)staining.The levels of angiotensinⅡ(AngⅡ),endothelin(ET),norepinephrine(NE),and thromboxane B_(2)(TXB_(2))were determined by enzyme linked immunosorbent assay(ELISA).The positive expression of AT1R in the thoracic aorta was detected by immunohistochemistry.The protein expressions of Nrf2,HO-1,and NQO1 in the thoracic aorta were detected by Western Blotting.Results Compared with the spontaneous hypertension group,systolic blood pressure in the low dose TanshinoneⅡA group,high dose TanshinoneⅡA group,and benazepril group decreased(P<0.05).The iniury of vascular endothelium and vascular elasticity in low dose TanshinoneⅡA group,high dose TanshinoneⅡA group,and benazepril group improved.Compared with the blank control group,the retinal artery diameter was slightly lessened in the spontaneously hypertensive group.The retinal artery diameter in the low dose TanshinoneⅡA group,high dose TanshinoneⅡA group,and benazepril group was wider.The levels of AngⅡ,ET,NE and TXB_(2) in the spontaneous hypertension group significantly increased(P<0.01).The levels of AngⅡ,ET,NE,and TXB_(2) in the low dose TanshinoneⅡA group,high dose TanshinoneⅡA group,and benazepril group decreased(P<0.05 or P<0.01).AngⅡreceptor(AT1R)positively expressed in the thoracic aorta of spontaneously hypertensive rats,and decreased in the low dose TanshinoneⅡA group,high dose TanshinoneⅡA group,and benazepril gr

关 键 词：自发性高血压 丹参酮ⅡA 血管活性物质 大鼠 实验研究 

分 类 号：R285.5[医药卫生—中药学]