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目的:研究黄芪多糖对自发性高血压大鼠(SHR)心功能和心肌纤维化的影响及其机制。方法:将50只SHR随机分为模型组、卡托普利组(阳性药物,30 mg/kg)和黄芪多糖高、中、低剂量组(100、50、25 mg/kg),每组10只;另选10只京都大鼠作为正常组。各给药组大鼠ip相应药物,正常组和模型组大鼠ip等体积蒸馏水,每天1次,连续12周。记录大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室内压最大上升速率(+dp/dtmax)、左室内压最大下降速率(-dp/dtmax);测定大鼠心脏质量指数(HMI)、左心室质量指数(LVMI);检测大鼠心肌组织羟脯氨酸含量以及转化生长因子β1(TGF-β1)、过氧化物酶体增生物激活受体γ(PPAR-γ)mRNA及其蛋白的表达。结果:与正常组比较,模型组大鼠LVSP、+dp/dtmax、-dp/dtmax降低,LVEDP、HMI、LVMI升高;心肌组织羟脯氨酸含量、TGF-β1 mRNA及其蛋白表达增加,PPAR-γ mRNA及其蛋白表达减少(P<0.01)。与模型组比较,黄芪多糖高剂量组和卡托普利片组大鼠上述指标均明显改善(P<0.05或P<0.01);黄芪多糖中剂量组大鼠除LVEDP、PPAR-γ mRNA外其余各指标均明显改善(P<0.05或P<0.01);黄芪多糖低剂量组大鼠仅-dp/dtmax明显升高、TGF-β1 mRNA表达明显降低(P<0.05),其余各指标差异均无统计学意义(P>0.05)。结论:黄芪多糖可改善SHR心功能和心肌纤维化,其机制可能与下调心肌组织TGF-β1表达、上调PPAR-γ表达有关。
OBJECTIVE: To investigate the effects of Astragalus polysaccharides on heart function and myocardial fibrosis in spontaneously hypertensive rats (SHR) and corresponding mechanism. METHODS: 50 SHR were randomly divided into a model group, a captopril tablets group (positive drug, 30 mg/kg) and the groups of high, medium and low-dose (100, 50, 25 mg/kg) Astragalus polysaccharides, with 10 SHR in each group. Another 10 Wistar Kyoto rats were included into the normal group. The rats in the drug administration groups were given corresponding drugs ip, while those in the normal group and the model group were given isometric distilled water ip, once a day, for 12 consecutive weeks. The left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), left ventricular pressure rise rate (+dp/dtmax) and left ventricular pressure decline rate (-dp/dtmax) of the rats were recorded. The heart mass index (HMI) and left ventricular mass index (LVMI) thereof were determined. The level of hydroxyproline and the mRNA and protein expression of transforming growth factor-β1 (TGF-β1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) in the cardiac muscle tissue thereof were detected. RESULTS: Compared to the normal group, the rats in the model group had lower LVSP, +dp/dtmax and -dp/dtmax, higher LVEDP, HMI and LVMI, as well as higher levels of hydroxyproline and the mRNA and protein expression of TGF-β1 and lower level of the mRNA and protein expression of PPAR-γ in the cardiac muscle tissue (P<0.01). Compared to the model group, all the above-mentioned indexes of the rats in the group of high-dose Astragalus polysaccharides and the captopril tablets group were significantly improved (P<0.05 or P<0.01); except for LVEDP and the mRNA expression of PPAR-γ, all the above-mentioned indexes of the rats in the group of medium-dose Astragalus polysaccharides were significantly improved (P<0.05 or P<0.01); no statistically significant difference (P>0.05) in all the above-mentioned indexes was shown between the model group and the group of low-dose Astragalus polysaccharides, except that the -dp/dtmax of the latter was significantly higher and the level of the mRNA expression of TGF-β1 was obviously lower (P<0.05). CONCLUSIONS: Astragalus polysaccharide can improve heart function and myocardial fibrosis in SHR by a mechanism which may be related to downregulating the expression of TGF-β1 and upregulating the expression of PPAR-γ in the cardiac muscle tissue.
黄芪多糖自发性高血压大鼠心功能心肌纤维化羟脯氨酸
Astragalus polysaccharidesSpontaneously hypertensive ratsHeart functionMyocardial fibrosisHydroxyproline
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