大黄素灌胃对原发性高血压大鼠心脏功能的改善作用及其机制

Improvement and mechanism of emodin on cardiac function in rats with primary hypertension

目的 观察大黄素对原发性高血压(SHR)大鼠心脏功能的改善作用,并探讨其可能机制.方法 SHR(收缩压≥140 mmHg或舒张压≥90 mmHg)大鼠10只分为A、B组各5只,WKY大鼠5只(C组),A组每天灌胃30 mg/kg的大黄素,其余两组灌胃大黄素溶剂—1%羧甲基纤维素钠溶液,维持10周.大鼠灌胃10周后,停药1 d,经颈总动脉插管检测大鼠血流动力学相关指标;大鼠处死后留取心脏和肾脏,qPCR检测心脏组织ANP、BNP、NPR-A、NPR-B mRNA及肾脏组织NPR-A、NPR-B、NPR-C mRNA,Western blotting法检测心脏组织bcl-2、bax、含胱冬肽酶富集功能域的凋亡抑制因子(ARC)蛋白.结果 与C组比较,B组HR、SBP、DBP、LVSP、dp/dtmax升高,-dp/dtmax降低(P均<0.05);与B组比较,A组LVEDP、-dp/dtmax升高,HR、dp/dtmax降低(P均<0.05).与C组比较,B组心脏ANP、BNP mRNA表达升高,肾脏组织NPR-C mRNA表达降低(P均<0.05);与B组比较,A组ANP、BNP、NPR-A mRNA表达降低,肾脏组织NPR-C mRNA表达升高(P均<0.05).与C组比较,B组心脏组织bcl-2、ARC蛋白及bcl-2/bax表达降低,bax表达升高(P均<0.05);与B组比较,A组bcl-2、ARC蛋白及bcl-2/bax表达升高(P均<0.05).结论 大黄素灌胃对SHR大鼠心脏功能有改善作用,其机制可能是通过调控钠尿肽系统和心肌细胞凋亡途径来实现.

Objective To observe the protective effects of emodin on the heart in spontaneously hypertensive rats (SHRs) and to explore its mechanism. Methods Ten SHRs ( systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) were divided into the group A and group B, and 5 WKY rats were taken as the group C. Rats in the group A were given 30 mg/kg of emodin and the other two groups with 1 % sodium carboxymethylcellulose solution daily by gavage for 10 weeks. With interval of one day after 10 weeks, the related parameters of hemodynamics were measured in carotid artery intubation, and the hearts and kidneys were set aside. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the mRNA levels of ANP, BNP, NPR-A, NPR-B in the cardiac tissues, as well as the mRNA levels of NPR-A, NPR-B and NPR-C in the renal tissues. Western blotting was used to detect apoptosis-related proteins, such as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and apoptosis repressor with caspase recruitment domain ( ARC). Results Compared with the group C, HR, SBP, DBP, LVSP, and dp/dtmax increased, while -dp/dtmax decreased in the group B ( all P <0.05). Compared with the group B, LVEDP and -dp/dtmax increased, while HR and dp/dtmax decreased in the group A ( all P <0. 05 ). Compared with the group C, the expression levels of heart ANP and BNP mRNA in the group B increased, while the expression of NPR-C mRNA in the kidney tissues decreased (all P < 0. 05). Compared with the group B, the expression levels of ANP, BNP and NPR-A mRNA in the group A decreased, while the expression of NPR-C mRNA in the kidney tissues increased (all P < 0. 05). Compared with the group C, the expression of Bcl-2, ARC protein and Bcl-2/Bax in the heart tissues of group B decreased, while the expression of Bax increased (all P <0.05). Compared with group C, the expression levels of Bcl-2, ARC protein and Bcl-2/Bax increased in the group B ( all P <0.05). Compared with group B, the expression levels of Bcl-2, ARC protein and Bcl-2/Bax in the group A increased ( all P <0.05). Conclusion Intragastric administration of emodin has a protective effect on the heart in SHRs possibly via the regulation of the natriuretic peptide system and myocardial apoptosis pathway.