葛根素对自发性高血压大鼠心肌纤维化的影响及其机制

摘要

目的：观察葛根素对自发性高血压大鼠（SHR）心肌局部血管紧张素II （Ang II）、巨噬细胞及心肌组织形态学的影响，探讨其保护心肌的可能机制。方法：35只12周龄SHR随机分为葛根素高、中、低剂量组（100 mg/kg、50 mg/kg、25 mg/kg，腹腔注射）、卡托普利组（30 mg/kg灌胃）和SHR对照组（生理盐水腹腔注射）。另设WKY空白对照组（生理盐水腹腔注射）。每组7只，给药6周。给药6周后麻醉下迅速处死取出心脏，称量左心室湿重后，备做Masson染色、组织匀浆和RT-PCR。结果：与WKY大鼠相比，SHR左室质量指数增高（P＜0．01），心肌组织Ang II含量上升（P＜0．01），单核细胞趋化蛋白1（MCP-1）和蛋白酶激活受体2（PAR2） mRNA表达增加（P＜0.01），巨噬细胞浸润明显（P＜0．01），间质纤维化严重（P＜0．01）。高剂量葛根素和卡托普利明显降低左室质量指数（P＜0．01），降低心肌Ang II含量（P＜0．01），下调MCP-1和PAR2 mRNA表达（P＜0．01），减少巨噬细胞浸润（P＜0．01或P＜0．05），减轻心肌间质纤维化（P＜0.01）。结论：葛根素具有治疗自发性高血压大鼠心肌纤维化作用，其机制可能与降低心肌局部Ang II含量、下调MCP-1和PAR-2 mRNA表达及减少巨噬细胞浸润有关。%AIM:To observe the effects of puerarin on the content of angiotensin II (Ang II), the macrophage infiltration and the fibrosis in the heart of spontaneously hypertensive rats (SHR).METHODS: Thirty-five 12-week-old SHR were randomly divided into high-, middle-and low-dose puerarin groups, in which the rats were intraperitoneally injec-ted with puerarin at dose of 100 mg/kg, 50 mg/kg and 25 mg/kg, respectively, captopril group (30 mg/kg,intragastric ad-ministration), and SHR control group.In addition, Wistar-Kyoto (WKY) rats were set up for control.In the 2 control groups, the same volume of saline was given intraperitoneally .The rats received drugs for 6 weeks.All rats were sacrificed under deep anesthesia.The left ventricle was weighed (wet weight), and the heart was used for Masson staining , tissue ho-mogenate preparation and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Com-pared with WKY group, the left ventricular mass index (LVMI) was increased, content of angiotensin II (Ang II) was high-er, the mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and protease-activated receptor 2 (PAR2) was both up-regulated, macrophage infiltration was marked, and collagen deposition was obvious in the heart of SHR control group.Compared with SHR control group , high-dose puerarin and captopril decreased LVMI and Ang II level , down-regula-ted mRNA expression of MCP-1 and PAR2, reduced macrophage infiltration , and improved collagen deposition in the heart . CONCLUSION:Puerarin attenuates myocardial fibrosis by decreasing the content of Ang II , down-regulating mRNA ex-pression of MCP-1 and PAR2 and inhibiting macrophage infiltration in the heart .