白藜芦醇通过调节沉默信息调节因子1/核转录因子-κB通路改善高血压左心室重塑

Resveratrol ameliorates hypertensive left ventricular remodeling by regulating the silent information regulator 1/nuclear transcription factor-κB pathway

摘要:

目的： 研究白藜芦醇（resveratrol，RES）对自发性高血压大鼠（spontaneous hypertension rat，SHR）左心室重塑的影响及其对沉默信息调节因子1（silent information regulator 1，SIRT1）/核转录因子κB（nuclear transcription factor-κB，NF-κB）信号通路的作用。方法： 将8只8周龄雄性Wistar-Kyoto（WKY）大鼠作为正常组（WKY组），将40只8周龄雄性SHR随机分为SHR组、RES组、EX527组、RES+EX527组、RES+吡咯烷二硫代氨基甲酸盐（pyrrolidine dithiocarbamate，PDTC）组，每组8只，予以相应药物干预12周。测量大鼠体质量、收缩压、心脏超声、左心室质量、左心室质量指数（left ventricular mass index，LVMI）、心肌胶原容积分数（collagen volume fraction，CVF）、氧化应激指标、SIRT1和NF-κB以及炎症因子蛋白表达水平，观察HE和Masson染色下的心脏形态病理改变。结果： 与WKY组[LVMI（2.12±0.10）mg/g，CVF（0.18±0.09）%，SIRT1蛋白表达量1.40±0.05，NF-κB蛋白表达量0.46±0.06]相比，SHR组[LVMI（3.07±0.07）mg/g，CVF（2.60±0.56）%，SIRT1蛋白表达量0.78±0.08，NF-κB蛋白表达量1.41±0.08]左心室重塑程度严重，氧化应激和炎症因子水平及NF-κB表达明显增加（P<0.05），而SIRT1表达降低（P<0.05）。RES组[LVMI（2.72±0.09）mg/g，CVF（1.10±0.30）%，SIRT1蛋白表达量0.99±0.07，NF-κB蛋白表达量0.98±0.12]较SHR组左心室重塑程度减轻，氧化应激和炎症因子水平及NF-κB表达降低（P<0.05），SIRT1表达增加（P<0.05）；而EX527组[LVMI（3.18±0.08）mg/g，CVF（2.83±0.98）%，SIRT1蛋白表达量0.60±0.02，NF-κB蛋白表达量1.68±0.07]结果与RES组相反。与RES组相比，RES+EX527组有逆转RES改善左心室重塑的趋势；而RES+PDTC组更有改善左心室重塑的趋势。结论： RES能改善SHR的左心室重塑，其机制可能与调节SIRT1/NF-κB通路从而减轻氧化应激和炎症反应损伤有关。

Abstract:

Objective: To study the effect of resveratrol (RES) on left ventricular remodeling in spontaneous hypertension rat (SHR) and its role in silent information regulator 1/nuclear transcription factor-κB (SIRT1/NF-κB) signaling pathway. Methods: Eight male Wistar-Kyoto (WKY) rats aged 8 weeks were taken as the normal group (WKY group), and 40 male SHR aged 8 weeks were randomly divided into SHR group, RES group, EX527 group, RES+EX527 group, and RES+pyrrolidine dithiocarbamate (PDTC) group, with 8 rats in each group, given corresponding drug intervention for 12 weeks. The rats’weight, systolic pressure, echocardiography, left ventricular mass, left ventricular mass index (LVMI), myocardial collagen volume fraction (CVF), oxidative stress index, SIRT1 and NF-κB protein expression levels, and inflammatory factors protein expression levels were measured. And the morphological and pathological changes of the heart under HE and Masson staining were observed. Results: Compared with WKY group[LVMI (2.12±0.10) mg/g, CVF (0.18±0.09) %, SIRT1 protein expression (1.40±0.05), NF-κB protein expression (0.46±0.06)], SHR group[LVMI (3.07±0.07) mg/g, CVF (2.60±0.56) %, SIRT1 protein expression (0.78±0.08), NF-κB protein expression (1.41±0.08)] showed severe left ventricular remodeling, significantly increased levels of oxidative stress and inflammatory factors as well as NF-κB expression (P<0.05), and decreased SIRT1 expression (P<0.05). In RES group[LVMI (2.72±0.09) mg/g, CVF (1.10±0.30) %, SIRT1 protein expression (0.99±0.07), NF-κB protein expression (0.98±0.12)], compared with SHR group, left ventricular remodeling degree was reduced, oxidative stress and inflammatory factors as well as NF-κB expression levels were decreased (P<0.05), and SIRT1 expression was increased (P<0.05). The results of EX527 group[LVMI (3.18±0.08) mg/g, CVF (2.83±0.98) %, SIRT1 protein expression (0.60±0.02), NF-κB protein expression (1.68±0.07)] were opposite to those of RES group. Compared with RES group, RES+EX527 group showed a trend of reversing RES to ameliorate left ventricular remodeling. RES+PDTC group showed a tendency to further ameliorate left ventricular remodeling. Conclusion: RES can ameliorate left ventricular remodeling of SHR, and its mechanism may be related to regulation of SIRT1/NF-κB pathway to reduce oxidative stress and inflammatory response damage.