摘要
目的 观察天麻芎苓止眩片对自发性高血压大鼠(SHR)血管内皮损伤的保护作用。方法 30只SHR以随机分层方式分为模型组(蒸馏水)、阳性对照组(7.6 mg·kg^(-1)卡托普利片)、实验组(1.0 g·kg^(-1)天麻芎苓止眩片),每组10只;另取10只Wistar-kyoto(WKY)大鼠为空白对照组。连续灌胃6周,观察各组大鼠血压变化,以苏木精-伊红(HE)染色检测胸主动脉形态学变化,以酶联免疫吸附实验法检测血清一氧化氮(NO)、内皮素(ET^(-1))水平,以免疫组化、蛋白质印迹法检测胸主动脉组织中细胞外调节蛋白激酶(ERK1/2)、环腺苷酸效应元件结合蛋白(CREB)、肌球蛋白样Bcl-2结合蛋白(Beclin1)的表达,检测胸主动脉组织中自噬微管相关蛋白轻链3(LC3)、细胞自噬相关蛋白8(Atg8)的表达。结果 空白对照组、模型组、阳性对照组和实验组血压分别为(114.49±4.83)、(200.25±28.49)、(135.62±14.30)和(138.55±13.33)mmHg;这4组血清NO含量分别(34.41±2.48)、(25.48±1.12)、(28.65±2.42)和(29.68±1.67)μmol·L^(-1);血清ET^(-1)含量分别为(129.28±15.49)、(188.58±16.74)、(152.65±13.32)和(142.26±9.76)μg·L^(-1);这4组胸主动脉组织中ERK1/2蛋白表达水平分别为0.92±0.05、3.41±0.11、2.46±0.30和0.88±0.10;CREB蛋白表达水平分别为1.03±0.12、3.58±0.09、2.11±0.14和0.94±0.08;Beclin1蛋白表达水平分别为0.83±0.02、3.98±0.16、2.05±0.15和2.87±0.10;Atg8蛋白表达水平分别为0.94±0.05、3.23±0.30、1.66±0.21和1.43±0.32;LC3Ⅱ/LC3Ⅰ的表达水平分别为0.21±0.04、3.50±0.35、0.77±0.29和0.54±0.12。以上指标,模型组与阳性对照组、实验组比较,差异均有统计学意义(均P<0.05)。结论 天麻芎苓止眩片可通过抑制ERK1/2-CREB通路调节血管内皮自噬失衡,逆转内皮损伤而降低血压。
Objective To observe the protective effect of tianma Xiongling Zhixuan tablet on vascular endothelial injury of spontaneous hypertension rat(SHR).Methods Thirty SHRs were randomly divided into model group(distilled water),positive control group(7.6 mg·kg^(-1)captopril tablet)and experimental group(1.O g·kg^(-1)Tianma Xiongling Zhixuan tablet)with 10 SHRs in each group.Ten Wistar-kyoto(WKY)rats were selected as blank control group.After 6 weeks of continuous intragastric administration,blood pressure changes of each group were observed,morphological changes of thoracic aorta were detected by hematoxylin-eosin(HE)staining,serum levels of nitrogen monoxide(NO)and endothelin^(-1)(ET^(-1))were detected by enzyme linked immunosorbent assay(ELISA),and protein expressions of extracellular-regulated kinase 1/2(ERK1/2),cAMP-response element binding protein(CREB)and Beclinl in thoracic aorta were detected by immunohistochemistry and Western blotting.Protein expressions of autophagy-related 8 protein(Atg 8)and microtubule-associated protein 1 light chain 3(LC3)in thoracic aorta were detected by Western blot.Results The blood pressure of blank control group,model group,positive control group and experimental group were(114.49±4.83),(200.25±28.49),(135.62±14.30)and(138.55±13.33)mmHg,respectively.The serum NO contents in the four groups were(34.41±2.48),(25.48±1.12),(28.65±2.42),and(29.68±1.67)μmol·L^(-1),respectively.The serum ET^(-1)content was(129.28±15.49),(188.58±16.74),(152.65±13.32)and(142.26±9.76)μg·L^(-1),respectively.The expression levels of ERK1/2 protein in thoracic aorta tissues of the four groups were 0.92±0.05,3.41±0.11,2.46±0.30 and 0.88±0.10;the expression levels of CREB protein were 1.03±0.12,3.58±0.09,2.11±0.14 and 0.94±0.08,respectively.Beclinl protein expression levels were 0.83±0.02,3.98±0.16,2.05±0.15 and 2.87±0.10,respectively.Atg8 protein expression levels were 0.94±0.05,3.23±0.30,1.66±0.21 and 1.43±0.32,respectively.The expression levels of LC3 I/LC3 I were 0.21±0.04,
作者
雍苏南
房赤
李苏
刘建和
YONG Su-nan;FANG Chi;LI Su;LIU Jian-he(Department of Cardiovascular,The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410007,Hunan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第9期1252-1256,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(81804077)
“重大新药创制”国家科技重大专项基金资助项目(2019ZX09301103)
湖南省卫生健康委科研课题基金资助项目(202103011378)
湖南省教育厅一般项目基金资助项目(20C1437)
湖南省教育厅优秀青年基金资助项目(22B0357)
中医学一流学科开放基金资助项目(2021ZYX06、2021ZYX30)。
关键词
天麻芎苓止眩片
自发性高血压大鼠
自噬
内皮损伤
信号通路
Tianma Xiongling Zhixuan tablet
spontaneous hypertension rat
autophagy
endothelial injury
signaling pathway
