Apocynin抑制慢性心力衰竭兔心肌纤维化的实验研究  

The Experimental Study of Anti-fibrotic Effects of Apocynin in Rabbits with Chronic Heart Failure

作　　者：夏文芳[1,2] 刘育[1] 李海涛[1] 黄从新[1] 

机构地区：[1]武汉大学人民医院心内科,武汉430060 [2]武汉大学人民医院重症医学科,武汉430060

出　　处：《微循环学杂志》2013年第1期1-4,11,F0002,I0001,共7页Chinese Journal of Microcirculation

基　　金：国家自然科学基金项目资助(81100129)

摘　　要：目的:探讨NADPH氧化酶抑制剂Apocynin对心衰兔心肌纤维化的影响及其机制。方法:32只兔随机分为假手术安慰剂组、假手术Apocynin组、心衰安慰剂组、心衰Apocynin组。通过容量超负荷联合压力超负荷建立家兔心衰模型。安慰剂或Apocynin以15mg/天口服。8周后,行超声心动图检查,观察动物的心脏结构和功能变化。通过细胞色素C还原试验测定心肌NADPH氧化酶活性。通过组织形态学分析心肌纤维化程度。运用Real-timePCR检测心肌转化生长因子β(TGF-β)、结缔组织生长因子(CTGF)、基质金属蛋白酶-2(MMP-2)和MMP-9基因表达。结果:与假手术安慰剂组比较,心衰安慰剂组心脏明显扩大,心功能明显降低(P<0.05),心肌NADPH氧化酶活性增加(P<0.05),心肌纤维化显著(P<0.05),TGF-β、CTGF、MMP-2和MMP-9表达上调(P<0.05)。与心衰安慰剂组比较,心衰Apocynin组心功能显著改善(P<0.05),心肌NADPH氧化酶活性明显降低(P<0.05),心肌纤维化显著减轻(P<0.05),心肌TGF-β、CTGF、MMP-2和MMP-9表达明显降低(P<0.05)。结论:Apocynin可通过下调心肌TGF-β、CTGF、MMP-2和MMP-9基因表达,改善心衰兔心肌纤维化。Objective: To investigate the effects and mechanisms of Apocynin, a NADPH oxidase inhibitor, on myocardial fibrosis in rabbits with chronic heart failure(HF). Method: Thirty-two rabbits were randomly divided into four groups: sham-operated placebo group, sham-operated Apocynin group, HF placebo group and HF Apocynin group. HF was induced by volume overload combined with pressure overload. The animals were orally administrated by Apocynin and placebo with a daily dose of 15 mg, respectively. Eight weeks later, cardiac function and structure was measured by echocardiography. NADPH oxidase activity was evaluated by superoxide dismutase (SOD)-inhibitable cytochromec reduction assays. Cardiac fibrosis was evaluated by masson’s trichrome staining. The expression of transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF) and matrix metalloproteinases (MMP-2 and MMP-9) were measured by real-time PCR. Results: Compared with sham-operated placebo group, the rabbits in the HF placebo group exhibited significant cardiac dilation and dysfunction (P<0.05), increased myocardial NADPH oxidase activity (P<0.05), more myocardial fibrosis (P<0.05), and increased expression of myocardial TGF-β, CTGF, MMP-2 and MMP-9 (P<0.05). Apocynin treatment improved cardiac function (P<0.05), decreased myocardial NADPH oxidase activity (P<0.05), attenuated the myocardial fibrosis (P<0.05), and decreased the expression of myocardial TGF-β, CTGF, MMP-2 and MMP-9 (P<0.05, respectively) in rabbits with HF. Conclusion: Apocynin treatment can decrease myocardial fibrosis in rabbits with HF by downregulating TGF-β, CTGF, MMP-2 and MMP-9 expression.

关 键 词：APOCYNIN 心力衰竭 NADPH氧化酶 纤维化 

分 类 号：R542.23[医药卫生—心血管疾病]