丹参对自发性高血压大鼠炎症因子干预作用的实验研究

Experiment research on intervention of Salvia miltiorrhiza on inflammatory factors in rats with spontaneous hypertension

目的初步探讨炎症反应在高血压左室重构中的作用,以及中药丹参对自发性高血压大鼠(SHR)左室重构的干预作用与机制。方法选用SHR 8周龄40只,随机分为模型对照组、治疗组(丹参+络活喜)、西药对照组(络活喜)、中药对照组(牛黄降压丸+络活喜)4组,并以SD大鼠10只作为对照组。疗程20周。观察各组血压及测定心脏重量指数(HWI);HE染色观察病理学改变;采用放射免疫法检测大鼠血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的表达水平。免疫组化法及RT-PCR检测心肌组织内转化生长因子-β1(TGF-β1)蛋白及mRNA水平表达。结果丹参可显著减轻SHR心肌细胞肥大、心肌间质炎性细胞浸润,也有降低心脏重量指数的趋势,但对收缩压无明显改变。SHR血清中TNF-α、IL-6,心肌组织内TGF-β1蛋白及mRNA表达水平均较SD大鼠显著升高(P<0.01);治疗组与模型对照组比较可明显降低SHR的TNF-α、IL-6、TGF-β1表达水平(P<0.01),优于其他给药组。结论 SHR血清中TNF-α、IL-6和心肌组织内TGF-β1的过度表达参与了高血压左室重构的过程。中药丹参具有独立于降压之外的逆转SHR左室重构的作用,其机制可能与降低TNF-α、IL-6以及TGF-β1的表达水平有关。

Objective To initially explore the role of inflammatory response on left-ventricular （LV） remodeling in spontaneous hypertension, and the intervention effect and mechanism of TCM Salvia miltiorrhiza on LV remodeling in spontaneous hypertension rats （SHR）. Methods Forty 8-week SHR were selected and randomly divided into a model group, a treatment group, a medicine group and a TCM group, and another 10 SD rats were selected＇s a control group. The intervention was required for 20 weeks. The blood pressure and heart weight index （HWI） were observed in each group, and pathological changes were observed with HE staining method. The expression levels of interleukin-6 （IL-6） and tumornecrosis factor-α （TNF-α） in serum were measured with radioimmunity method, and the protein and mRNA expression of transforming growth factor-β1（TGF-β1） was tested with immunohistochemical and RT-PCR method. Results Salvia miltiorrhiza could significantly relieve the hypertrophy of myocardial cell and infiltration of inflarmnatory cell in myocardial matrix, also it had a tendency to lower HWI, but no obvious change on systolic pressure. Compared with SD rats, the levels of TNF-α, IL-6 and protein and mRNA expression of TGF-β1 in SHR serum were significantly lifted （P 〈0. 01 ）. Compared with the model group, the level of TNF-α, IL-6 and expression of TGF-β1 was obviously decreased in the treatment group, which was superior to other treatment groups. Conclusion The TNF-α, IL-6 in serum and the over-expression of TGF-β1 in myocardium is involved in the process of LV remodeling in hypertension. The TCM Salvia miltiorrhiza has effects of reversing SHR LV remodeling, which is independent of depressurization. The mechanisms may be related with lowering TNF-α, IL-6 and expression of TGF-β1.