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To observe the efficacy of ethyl acetate extracts of Tribulus terrestris (TT) on left ventricular hypertrophy of spontaneous hypertensive rats and to explore its pharmacological mechanism on alleviating myocardial remodeling.
Thirty-two 16-week old male spontaneous hypertensive rats (SHRs) were randomly divided into high dosage of TT (17.2mg·kg-1·d-1) group, low dosage of TT (8.6mg·kg-1·d-1) group, valsartan (13.35mg·kg-1·d-1) group and model group. And eight normotensive WKY rats were used as normal control. Rats in drug intervention groups were intragastrically administrated their respective drugs and rats in model group and WKY rats were given the same volume of saline intragastrically for 12 weeks. Body weight and blood pressure were measured every week. The echocardiography was recorded every two weeks. The level of angiotensinII (AngII), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), nitric oxide (NO) in myocardial homogenate were determined by ELISA. Morphological changes of left ventricular observed by HE staining and transmission electron microscope. The distribution of angiotensinII receptor 1 (AT1) and transforming growth factor (TGF-β) was detected by immuonhistochemical staining assay. Activated reactive oxygen species (ROS) generation in tissues was assessed by immunofluorescence. The level of mRNA expression of MAPK, ERK1, ERK2, AT1 and ACE were determined by quantitive real-time PCR to explore the possible mechanism of TT on alleviating myocardial hypertrophy. The expression of p-c-Raf and p-ERK1/2 were assayed by western blotting.
After drug administration for 12 weeks, high dosage of TT and valsartan decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate of SHR significantly (P＜0.05). The level of interventricular septal thickness (IVSd), left ventricular posterior wall thickness (LVPWTd), left ventricular mass (LVM), left ventricular mass index (LVMI) was decreased significantly while left ventricular end diastolic diameter (LVEDd) was increased (P＜0.05). The myocardial AngII, TNF-α and IL-6 was decreased, while NO was increased significantly (P＜0.05). The myocardial morphology was improved, the distribution of AT1 and TGF-β was decreased and the level of ROS was decreased in different degree after drug treatment. The mRNA expression of MAPK, ERK1, ERK2, AT1 and ACE of myocardium in high dosage TT and valsartan group was decreased significantly (P＜0.05). The protein expression of p-c-Raf and p-ERK1/2 was decreased significantly (P＜0.05).
TT improved cardiac function effectively and alleviated the ventricular hypertrophy in SHR. Downregulation of MAPK pathway and inhibition of RAS may contribute to the possible pharmacological mechanism of TT.