氟西汀对大鼠右心衰竭肺动脉高压的影响及机制探讨

Effects of Fluoxetine on Nogo Expression and Collagen Production with Decrease of Pulmonary Artery Pressure in Rats with Right Ventricular Failure

目的探讨氟西汀干预肺动脉压对右心衰竭大鼠心肌组织轴索生长抑制因子(Nogo)和胶原的影响。方法将31只SD雄性大鼠随机分为治疗组、右心衰竭组、对照组。治疗组和右心衰竭组一次性腹腔注射野百合碱60mg/kg诱发肺动脉高压致右心衰竭,对照组腹腔注射等量生理盐水。治疗组大鼠腹腔注射21d后给予氟西汀10mg/(kg·d)灌胃,直到第42天。右心衰竭组和对照组给予等量生理盐水灌胃。HE染色观察各组大鼠肺动脉和右心室心肌组织,Masson染色观察右心室心肌组织胶原生成情况。采用实时荧光定量PCR检测各组大鼠心肌组织Nogo-A、Nogo-B、Ⅰ型胶原和Ⅲ型胶原mRNA的表达,同时采用Western blot方法对Nogo蛋白进行半定量分析。结果氟西汀干预后,HE染色可见肺动脉狭窄明显减轻,右心室心肌组织病变减轻,Masson染色示右心室心肌组织胶原合成减少。实时荧光定量PCR结果显示,与右心衰竭组比较,治疗组心肌组织Ⅰ型和Ⅲ型胶原mRNA表达下降,Nogo-A mRNA降低,Nogo-B mRNA上升(P均<0.05)。Western blot结果显示,与右心衰竭组比较,治疗组心肌组织Nogo-A蛋白表达降低,Nogo-B1蛋白表达增加(P均<0.05),Nogo-B2蛋白表达无明显变化(P>0.05)。结论 Nogo可能影响右心衰竭的胶原合成,部分参与心肌纤维化。

Objective To investigate the effect of fluoxetine on neurite growth inhibitor （Nogo） expession and collagen production of cardiac tissue in rats with right heart failure and pulmonary hypertension. Methods Thirty one male SD rats were randomly divided into the treatment group, right heart failure group and normal control group. The rats in the treatment group and right heart failure group received intrapertioneal injection of monocrotaline （MCT, 60 mg/kg） to induce pulmonary hypertension and right heart failure. After 21 days, the rats in treatment group were given fluoxetine of 10 mg/（kg · d） by gavage per day for 21 days, the rats in the other two groups were given saline. HE staining was used to observe the pulmonary artery and right ventricular myocardial tissue in rats. The collagen formation in right ventricular myocardium was observed by Masson staining. The expressions of Nogo-A,Nogo-B, type I collagen and type Ⅲ collagen mRNA in myocardium were measured by real- time fluorescence quantitative PCR, while the semi quantitative measurement of Nogo protein level was detected by Western blot. Results After the intervention of fluoxetine, pulmonary artery stenosis was significantly reduced, myocardial tissue lesion decreased, collagen synthesis decreased in right ventrieular myocardium. RT-PCR showed that mRNA of Nogo-A decreased, and mRNA of Nogo-B increased （P〈0. 05）. Western blot showed that the expression of Nogo-A protein decreased, while Nogo-B1 protein expression increased （P 〈 0. 05）, Nogo-B2 expression was not significantly changed （P〈0.05）. Conclusion Nogo may affect the collagen synthesis in right heart failure, and partly involved in myocardial fibrosis.