川芎嗪对两肾一夹高血压模型大鼠心肌的保护作用及机制  

Protective effect of ligustrazine on myocardium and its pathway in two-kidney-one-clip hypertensive rats model

作　　者：关丽文 黄良玖 赵红梅 张爽 GUAN Li-wen;HUANG Liang-jiu;ZHAO Hong-mei;ZHANG Shuang(Department of Clinical Pharmacy,Hainan Cancer Hospital,Haikou,Hainan 570000,China)

机构地区：[1]海南省肿瘤医院临床药学室,海南海口570000

出　　处：《中华高血压杂志》2022年第4期364-370,共7页Chinese Journal of Hypertension

摘　　要：目的 探讨川芎嗪对两肾一夹高血压模型大鼠心肌的保护作用及对Ras同源基因家族蛋白A(RhoA)/Rho相关卷曲螺旋蛋白激酶(ROCK)通路的影响。方法 通过两肾一夹法构建高血压大鼠模型,将SD雄性大鼠50只随机分成5组:假手术组(灌胃等量生理盐水),模型组(造模成功后灌胃等量生理盐水),坎地沙坦组[造模成功后灌胃10 mg/(kg·d)坎地沙坦],川芎嗪低、高剂量组[造模成功后分别灌胃30、50 mg/(kg·d)川芎嗪],每组各10只。每日1次,连续给药4周。通过血压仪测量给药2、4周后各组大鼠动脉收缩压、心率。末次给药24 h后,酶联免疫吸附试验(ELISA)法检测各组大鼠血浆中内皮素1、血管紧张素Ⅱ(AngⅡ)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)含量,HE染色观察各组大鼠左心室心肌细胞形态变化,Masson染色观察心肌胶原组织结构变化,计算心肌胶原容积分数(CVF),实时荧光定量聚合酶链反应和Western blot检测各组大鼠左心室组织RhoA、ROCK1、转化生长因子β;(TGF-β;)mRNA及蛋白表达情况。结果与假手术组相比,干预前,干预2、4周,模型组大鼠收缩压、心率升高(均P<0.05)。干预2、4周,与模型组相比,坎地沙坦组,川芎嗪低、高剂量组大鼠收缩压、心率降低(P<0.05);坎地沙坦组和川芎嗪高剂量组大鼠收缩压低于川芎嗪低剂量组(均P<0.05)。与假手术组相比,模型组大鼠出现心肌细胞排列紊乱、细胞间隙不明显、纤维组织增生、排列不规则、有大量蓝色胶原组织表达等病理变化,心肌CVF升高;与模型组相比,坎地沙坦组,川芎嗪低、高剂量组大鼠上述病理变化明显减轻,心肌CVF降低[心肌CVF:坎地沙坦组(1.71±0.15)%比川芎嗪高剂量组(1.76±0.21)%比川芎嗪低剂量组(3.53±0.37)%比模型组(4.72±0.43)%比假手术组(1.15±0.10)%,F=230.903,P<0.001]。与假手术组相比,模型组大鼠血浆内皮素1、AngObjective To explore the protective effect of ligustrazine on myocardium through Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil forming protein kinase(ROCK) pathway in two-kidney-one-clip hypertensive rats model. Methods The hypertensive model was established in rats by two-kidney-one-clip method. Fifty male SD rats were randomly divided into five groups: sham operation group(oral gavage with the same amount of normal saline), model group(oral gavage with the same amount of normal saline), candesartan group [oral gavage with 10 mg/(kg·d) candesartan], ligustrazine low and high dose groups [oral gavage with 30 mg/(kg·d) and 50 mg/(kg·d) ligustrazine, respectively], with 10 rats in each group. All rats were administered once a day for consecutive 4 weeks. Systolic blood pressure and heart rate were measured by sphygmomanometer after 2 and 4 weeks intervention, respectively. At 24 hours after the last administration, the plasma endothelin-1(ET-1), angiotension Ⅱ(AngⅡ), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI) were detected by enzyme-linked immunosorbent assay(ELISA), the morphological changes of left ventricular cardiomyocytes was observed after hematoxylin and eosin(HE) staining, the changes of collagen tissue structure was observed after Masson staining, collagen volume fraction(CVF) was calculated, and the mRNA and protein expressions of RhoA, ROCK1, transforming growth factor-beta 1(TGF-β;) in left ventricular tissue were detected by real-time quantitative reverse transcription polymerase chain reaction(PCR) and Western blot. Results The systolic blood pressure and heart rate of rats in the model group were significantly higher than that in the sham operation group before administration and after 2 and 4 weeks intervention(P<0.05), respectively. In addition, compared with the model group, both two measurements of rats were lower in candesartan group, low and high dose ligustrazine group after 2 and 4 weeks intervention(P

关 键 词：川芎嗪 坎地沙坦 Ras同源基因家族蛋白A(RhoA)/Rho相关卷曲螺旋蛋白激酶(ROCK)通路 两肾一夹 高血压 大鼠 心肌损伤 

分 类 号：R285.5[医药卫生—中药学]