颐脑解郁方对出血性脑卒中后焦虑大鼠磁共振波谱的干预作用

Effects of Yi'nao Jieyu formula on magnetic resonance spectroscopy of rats with post-stroke anxiety

目的通过应用磁共振波谱观察卒中后焦虑(PSA)大鼠脑代谢的变化情况和颐脑解郁方的干预作用。方法将Wistar大鼠随机分为正常组、模型组、假手术组、颐脑解郁方组。采用右侧尾壳核注射胶原酶联合不确定空瓶饮水刺激造成PSA模型。假手术组在右侧尾壳核注射等量生理盐水。造模结束后,颐脑解郁方组连续灌胃4周颐脑解郁方(4.19 g/kg),正常组、模型组和假手术组灌胃蒸馏水(10 m L/kg)。在造模结束后(第1天)及灌胃4周后观察大鼠表征及行为学(高架十字迷宫)。最后行磁共振波谱成像扫描每只大鼠的双侧前额叶皮质和海马,并分别记录N-乙酰天冬氨酸(NAA)、含胆碱代合物(Cho)、肌醇(m I)、谷氨酸(Glu)与肌酸(Cr)的相对含量。结果 (1)表征变化:模型组大鼠较正常组饮食不积极,皮毛凌乱干枯无光泽,梳理毛发和探究行为较少,易激惹,可见攻击行为、撕咬鼠笼等行为。颐脑解郁方组较模型组大鼠修饰行为增加,攻击行为明显减少,毛发较前顺滑,但不及正常组。(2)高架十字迷宫:模型大鼠在开放臂的时间和次数较正常组和颐脑解郁方组降低(P<0.05)。(3)磁共振波谱:模型大鼠右侧前额叶皮质NAA/Cr和Cho/Cr较正常组降低(P<0.05,P<0.01),Glu/Cr较正常组升高(P<0.05);左侧前额叶皮质和双侧海马各代谢物变化不明显(P>0.05)。颐脑解郁方组与模型组比较,NAA/Cr和Cho/Cr的水平升高(P<0.05),Glu/Cr降低(P<0.05)。结论颐脑解郁方可以调节PSA导致的脑代谢异常,改善卒中后大鼠的焦虑状态,其机制与降低兴奋性神经递质Glu的含量及修复受损神经元有关。

Objective To observe metabolism changes in rats with post-stroke anxiety（ PSA） and effects of Yi＇nao Jieyu（ brain-benefiting depression-resolving,YNJY） formula by using magnetic resonance spectroscopy. Methods Wistar rats were randomly divided into normal group,model group,sham-operation group,and YNJY group. PSA model was established by injecting collagenase（ type VII） into the right globus pallidus combined with empty water bottle stimulation. Saline was injected instead of collagenasein rats of the sham-operation group. Rats in the YNJY group received YNJY formula（ 4. 19 g/kg） for 4 weeks afterwards while those in the normal,model,and sham-operation groups were given distilled water（ 10 mL/g）. Morphology and behavior（ elevated plus maze） were observed after 4 weeks. Magnetic resonance spectroscopy was utilized at week 4 as well. Magnetic resonance spectroscopy imaging was the last one to be detected. Bilateral prefrontal cortex and hippocampus were scanned in each rat and the relative contents of N-acetylaspartic acid（ NAA）,choline-containing compounds（ Cho）,myoinositol（ mI）,glutamate（ Glu） and creatine（ Cr） were recorded. Results 1. Morphology： Compared with the normal group,rats in the model group ate less,hadmessy and dull fur,behaved aggressively,and gnawed the cage frequently. Compared with the model group,rats in the YNJY group had less aggressive behaviors,and their fur appeared softer and smoother. 2. Elevated plus maze： entry into and duration in open arms were statistically significantly less in the model group than the normal and CM group（ P〈0. 05）. 3. Magnetic resonance spectroscopy： model rats had lower level of NAA/Cr and Cho/Cr,and higher level of Glu/Cr in the right pre-frontal cortex than normal rats（ P〈0. 05,P〈0. 01）,but there was no significant differences in left pre-frontal cortex and both hippocampi（ P〉0. 05）. Compared with the model group,levels of NAA/Cr and Cho/Cr were higher in the YNJY group,while Glu/Cr level was lower in the right pre-frontal cortex（ P〈0. 05）. Conclusion YNJY formula could restore cerebral metabolism caused by PSA,relieve the post-stroke anxiety,the mechanism of which may be related with reducing amino acid neurotransmitters and repairing of impaired neurons.