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番石榴叶总黄酮对高血压模型大鼠心肌肥厚的改善作用 Δ

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余淑华 ，何春琳 ，张 培 ，杨东伟（1.郑州大学附属郑州中心医院高血压科，郑州 450007；2.郑州大学附属
郑州中心医院心内科，郑州 450007）
中图分类号 R285.5 文献标志码 A 文章编号 1001-0408（2022）02-0191-06
DOI 10.6039/j.issn.1001-0408.2022.02.11

摘 要 目的 研究番石榴叶总黄酮对高血压模型大鼠心肌肥厚的改善作用。方法 从60只健康SD大鼠中随机取10只作为正常
组；另外50只大鼠复制高血压模型，将其中建模成功的44只采用随机体质量排序法分为模型组、茴香霉素组[p38丝裂原活化蛋白
激酶（p38 MAPK）激活剂，1 mg/kg]、番石榴叶总黄酮+茴香霉素组（200 mg/kg番石榴叶总黄酮+1 mg/kg茴香霉素）、番石榴叶总黄
酮组（200 mg/kg），每组11只。正常组和模型组大鼠灌胃3％羟甲基纤维素钠溶液，其余各组大鼠灌胃相应药液，每天1次，连续6
周。检测大鼠血压（收缩压、舒张压、平均动脉压）水平和心脏指数、左心室指数；检测大鼠心肌组织中肿瘤坏死因子α（TNF-α）、白
细胞介素1β（IL-1β）、IL-6水平；观察大鼠心肌组织的病理形态学变化；检测大鼠心肌组织中p38 MAPK、磷酸化p38 MAPK（p-p38
MAPK）、细胞外调节蛋白激酶1/2（ERK1/2）、磷酸化ERK1/2（p-ERK1/2）、c-Jun氨基末端激酶（JNK）、磷酸化JNK（p-JNK）蛋白的
表达水平。结果 与正常组比较，茴香霉素组、模型组大鼠的收缩压、舒张压、平均动脉压水平，心脏指数、左心室指数和心肌组织
中TNF-α、IL-1β、IL-6水平以及p-p38 MAPK、p-ERK1/2、p-JNK蛋白的表达水平均显著升高（P＜0.05）；心肌细胞肥大，心肌纤维走
向紊乱，心肌纤维间结缔组织疏松水肿、增生，炎症细胞浸润增多等。与茴香霉素组、模型组比较，番石榴叶总黄酮+茴香霉素组、
番石榴叶总黄酮组大鼠上述指标水平均显著降低（P＜0.05）；心肌细胞稍大、排列尚可，心肌细胞肥大程度及结缔组织疏松水肿、
增生情况减轻，且番石榴叶总黄酮组的改善效果更为显著（P＜0.05）。结论 番石榴叶总黄酮可降低高血压模型大鼠的血压水平，
并改善其心肌肥厚，其作用机制可能与抑制p38 MAPK信号通路活性及炎症因子表达有关。
关键词 番石榴叶总黄酮；高血压；心肌肥厚；p38 丝裂原活化蛋白激酶；炎症因子；大鼠

Improvement effects of total flavonoids of Psidium guajava leaves on myocardial hypertrophy in
hypertensive model rats
YU Shuhua ，HE Chunlin ，ZHANG Pei ，YANG Dongwei （1. Dept. of Hypertension，Zhengzhou Central
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Hospital Affiliated to Zhengzhou University，Zhengzhou 450007，China；2. Dept. of Cardiovascular Medicine，
Zhengzhou Central Hospital Affiliated to Zhengzhou University，Zhengzhou 450007，China）
ABSTRACT OBJECTIVE To study the improvement effects of total flavonoids of Psidium guajava leaves on myocardial
hypertrophy in hypertensive model rats. METHODS Ten rats were randomly selected from 60 healthy SD rats as the normal group；
other 50 rats established hypertensive model，and 44 rats with successful modeling were randomly divided into model group，
anisomycin group [p38 mitogen-activated protein kinase（p38 MAPK）activator，1 mg/kg]，total flavonoids of P. guajava leaves+
anisomycin group（200 mg/kg total flavonoids+1 mg/kg anisomycin）and total flavonoids of P. guajava leaves group（200 mg/kg）
by random volume mass ranking method，with 11 rats in each group. Rats in normal group and model group were given 3％
hydroxymethylcellulose sodium solution， and other groups were given relevant solution intragastrically， once a day， for
consecutive 6 weeks. Blood pressure（systolic blood pressure，diastolic blood pressure，mean arterial pressure），cardiac index and
left ventricular index were measured. The levels of tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β）and IL-6 in myocardial
tissue were detected. The pathomorphological changes of myocardial tissue were observed. The expression of p38 MAPK，
phosphorylated p38 MAPK （p-p38 MAPK），extracellular regulated protein kinase 1/2 （ERK1/2），phosphorylated ERK1/2
（p-ERK1/2），c-Jun N-terminal kinase（JNK）and phosphorylated JNK（p-JNK）in myocardial tissue were detected. RESULTS
Compared with normal group，the systolic blood pressure，diastolic blood pressure，mean arterial pressure，cardiac index，left
ventricular index as well as the levels of TNF-α，IL-1β and IL-6 and protein expression of p-p38 MAPK，p-ERK1/2 and p-JNK in
myocardial tissue were increased significantly in anisomycin group and model group（P＜0.05）；it was also found that hypertrophy
of cardiomyocytes，disorder of myocardial fibers，looseness，edema and proliferation of connective tissue between myocardial
fibers，increased infiltration of inflammatory cells，etc. Compared with anisomycin group and model group，the levels of above
indexes in total flavonoids of P. guajava leaves + anisomycin
Δ 基金项目：河南省医学科技攻关计划（联合共建）项目（No.
group and total flavonoids of P. guajava leaves group were
LHGJ20191058）
＊副主任医师。研究方向：冠心病、高血压。E-mail：lcx110_xcl@ decreased significantly （P＜0.05） ； cardiomyocytes were
163.com slightly larger and arranged reasonably；the degree of myocardial

中国药房 2022年第33卷第2期 China Pharmacy 2022 Vol. 33 No. 2 ·191 ·