高脂血症加重慢性心力衰竭大鼠抑郁样行为的作用机制

Mechanism of hyperlipidemia aggravating depression-like behavior in rats with chronic heart failure

目的探究高血脂加重慢性心力衰竭(下文简称心衰)大鼠抑郁样行为的作用机制。方法雄性SD大鼠32只分为假手术组、高脂血症组、心衰组、高脂血症合并心衰组,每组8只。高脂血症合并心衰组每日灌胃脂肪乳(10 mL/kg),诱导高脂血症,2周后行冠状动脉左前降支结扎术,术后继续灌胃脂肪乳4周;高脂血症组每日灌胃脂肪乳(10 mL/kg),手术时只穿线不结扎;假手术组和心衰组灌胃同等体积的生理盐水,手术处理分别同高脂血症组和高脂血症合并心衰组。术后4周,应用小动物超声、蔗糖偏好试验、旷场试验、ELISA、免疫荧光染色和Western blot等方法评价各组心衰程度、抑郁样行为、血脂和炎症水平、星形胶质细胞活化等指标变化。结果与假手术组相比,高脂血症组和高脂血症合并心衰组大鼠血脂升高(P<0.05);心衰组和高脂血症合并心衰组大鼠血浆脑钠肽含量升高(P<0.05),左室射血分数和左室短轴缩短率降低(P<0.05),蔗糖偏好指数、旷场试验自主活动总路程和平均速度降低(P<0.05),血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的含量及海马区胶质纤维酸性蛋白(GFAP)表达增高(P<0.05);与心衰组相比,高脂血症合并心衰组大鼠的蔗糖偏好指数、旷场试验自主活动总路程和平均速度降低(P<0.05),血浆TNF-α、IL-1β和IL-6的含量及GFAP的表达升高(P<0.05)。结论慢性心衰可诱发大鼠发生一定程度的抑郁样行为,高血脂能加重慢性心衰大鼠的抑郁样行为,其作用可能与高脂血症促进星形胶质细胞的活化和炎症因子的释放,导致神经炎症有关。

Objective To explore the effect and mechanism of hyperlipidemia on depression-like behavior in rats with chronic heart failure. Methods Thirty-two male SD rats were divided into sham operation group, hyperlipidemia(HLP) group, chronicheart failure(CHF) group, and hyperlipidemia combined with chronic heart failure(HLP + CHF) group(n=8). The HLP+CHF group was gavaged with fat emulsion 10 mL/kg daily for 2 weeks to induce hyperlipidemia.After 2 weeks, the left anterior descending coronary artery was ligated, and fat emulsion was intragastric administrated after operation for another 4 weeks to establish a rat model of chronic heart failure after myocardial infarction. In the HLP group, the rats were gavaged with fat emulsion 10 mL/kg daily, and the suture was only threaded without ligation. The sham group and CHF group were given the same volume of normal saline, and the surgical treatment was as same as that of the HLP and HLP+CHF groups respectively.After 4 weeks, echocardiography, sucrose preference test, open field test, ELISA, immunofluorescence staining and Western blot were used to evaluate heart failure degree, depression-like behaviors, blood lipids and inflammation levels, and degree of astrocyte activation, etc.Results Compared with that of the sham group, plasma TC and TG in the HLP group and HLP+CHF group were significantly increased(P<0.05),and in the CHF and HLP+CHF groups, plasma BNP content was significantly increased(P<0.05), the LVEF and LVFS were decreased(P<0.05), and the sucrose preference index and total distance and average speed of autonomous activity were significantly lower(P<0.05),the contents of plasma tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6) and the expression of glial fibrillary acidic protein(GFAP) in hippocampus were increased(P<0.05). Compared with that of the CHF group, the sucrose preference index and total distance and average speed of open field test were decreased, while plasma TNF-α, IL-1β, IL-6 content and GFAP expression were increased in the HLP + CHF group(P< 0.05).Conclusion Chronic heart failure could induce depression-like behavior to a certain extent in rats. Hyperlipidemia seems to aggravate depression-like behavior in rats with chronic heart failure, which may be related to neuroinflammation caused by the activation of astrocytes and the release of inflammatory factors.