活血潜阳祛痰方对肥胖高血压大鼠左室重构的影响

Effects of Huoxue Qianyang Qutan Recipe on left ventricular remodeling in obese and hypertensive rats

目的:观察活血潜阳祛痰方对肥胖高血压大鼠左室重构的干预作用,并探讨其作用机制。方法:以5周龄雄性自发性高血压大鼠(SHR)为对象,随机选取SHR 9只作为普食对照组(SHR组)予普通饮食,其余54只予高脂饮食共10周进行肥胖高血压大鼠模型造模并随机分为模型组、中药组和西药组;以周龄和性别相匹配的正常WKY大鼠为WKY对照组。中药组予活血潜阳祛痰方42 g·kg^(-1)·d^(-1)药液灌胃,西药组予缬沙坦30 mg·kg^(-1)·d^(-1)配液灌胃,WKY对照组、SHR组和模型组均用等容量饮用水灌胃,均灌胃2次/d,持续8周。观察体质量、血压、糖脂代谢指标、心肌血管紧张素(Ang)Ⅱ水平,观察大鼠左室重构、心肌结构和细胞凋亡情况;分别采用RTPCR和Western blot检测内质网分子伴侣葡萄糖调节蛋白78(glucose regulated protein,GRP78)、Caspase-12的mRNA和蛋白表达。结果:(1)与模型组比较,中药组和西药组大鼠血压(P<0.05,P<0.01)、空腹血糖(FPG)(P<0.01)、三酰甘油(TC)(P<0.05)、低密度脂蛋白(LDL-C)(P<0.01)水平均显著降低;(2)中药组大鼠体质量(P<0.05)、Lee’s指数(P<0.05)及胰岛素抵抗指数(HOME-IR)(P<0.01)均显著低于模型组;(3)中药组心脏质量指数(P<0.01)、左室质量指数(LVMI)(P<0.05)、心肌细胞凋亡率(P<0.05)均明显低于模型组。(4)SHR组心肌AngⅡ水平显著高于WKY对照组(P<0.01),模型组AngⅡ显著高于SHR组(P<0.01);中药组心肌AngⅡ水平明显低于模型组(P<0.01)。(5)模型组心肌GRP78、Caspase-12基因的mRNA和蛋白表达水平显著高于SHR组(P<0.01),中药组GRP78、Caspase-12基因的mRNA和蛋白表达水平均明显低于模型组(P<0.05,P<0.01)。结论:活血潜阳祛痰方可显著改善肥胖高血压大鼠肥胖状态、血压、糖脂代谢及左室重构,可能与其调控心肌局部AngⅡ-GRP78-Caspase-12凋亡信号通路的作用相关。

Objective: To observe the effects of Huoxue Qianyang Qutan Recipe on the left ventricular remodeling in obese and hypertensive rats,and discuss its mechanism. Methods: Five week-old male rats with spontaneous hypertension were taken. The obese and hypertensive rat model was established in 54 spontaneously hypertensive rats( SHR) by feeding high fat diet for 10 weeks. Then the modeling rats were randomly divided into the model group,Chinese medicine group and western medicine group,and 9 spontaneously hypertensive rats fed with normal diet were taken as the control group. The normal male Wistar-Kyoto rats with the same age and sex were taken as the normal group. The Chinese medicine group was treated with Huoxue Qianyang Qutan Recipe at daily dose of 42 g/kg by intragastric administration,the western medicine group was treated with valsartan at daily dose of 30 mg/kg by intragastric administration,the normal group,control group and model group were treated with equivalent drinking water by intragastric administration. The administration was performed twice a day for continuous 8 weeks. The body weight,blood pressure,glycolipid metabolism indexes,myocardial AngⅡ level were detected. The left ventricular remodeling,myocardial structure and cell apoptosis were observed. The mRNA and protein expressions of endoplasmic reticulum molecular chaperon glucose regulated protein( GRP) 78 and Caspase-12 were detected by RT-PCR and Western blot. Results:(1) The blood pressure and the levels of FPG,TC,LDL-C in the Chinese medicine group and western medicine group were significantly lower than those in the model group( P<0.05,P<0.01).(2)The body weight,Lee's index and HOME-IR index in the Chinese medicine group were significantly lower than those in the model group( P<0.05,P<0.01).(3)The cardiac mass index,left ventricular mass index and cardiomyocyte apoptosis rate in the Chinese medicine group were significantly lower than those in the model group( P< 0.05,P< 0.01).(4)The myocardial AngⅡ level in the control group was significantly higher than that in the normal group( P<0.01). The AngⅡ level in the model group was significantly higher than that in the control group( P<0.01). The AngⅡ level in the Chinese medicine group was obviously lower than that in the model group( P < 0. 01).(5) The mRNA and protein expression levels of myocardial GRP78 and Caspase-12 in the model group were significantly higher than those in the control group( P<0.01),and the mRNA and protein expression levels of GRP78 and Caspase-12 in the Chinese medicine group were obviously lower than those in the model group( P < 0. 05,P < 0. 01). Conclusion: Huoxue Qianyang Qutan Recipe could significantly improve the obese condition,blood pressure,glucose and lipid metabolism and left ventricular remodeling in obese and hypertensive rats. It may be associated with the regulation on myocardial Ang Ⅱ-GRP78-Caspase-12 apoptosis signaling pathway.