柴胡加龙骨牡蛎汤对心肌梗死合并焦虑大鼠HPA轴的影响

Effect of Chaihu and Longgu Muli Decoction on HPA Axis in Rats with Myocardial Infarction and Anxiety

目的探讨柴胡加龙骨牡蛎汤对心肌梗死合并焦虑大鼠下丘脑-垂体-肾上腺(HPA)轴的影响。方法将无特定病原体(SPF)级6周龄健康雄性SD大鼠36只随机分为心肌梗死组(10只)、复合模型组(心肌梗死模型合并焦虑模型,10只)、中药组(复合模型+龙骨牡蛎汤灌胃,10只)、假手术组(6只)。中药组在复合模型组基础上给予柴胡加龙骨牡蛎汤灌胃,其余各组给予蒸馏水灌胃。超声心动图检测左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室短轴缩短率(LVFS)、左室射血分数(LVEF);旷场试验和高架十字迷宫检测大鼠行为学;电镜观察心肌梗死边缘区心肌组织Masson染色和海马尼氏染色变化;酶联免疫吸附试验(ELISA)检测大鼠外周血HPA促肾上腺皮质激素释放激素(CRF)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量。结果与假手术组比较,心肌梗死组与复合模型组LVEF及LVFS明显下降,LVESD和LVEDD明显升高(P<0.01);与复合模型组比较,中药组LVEF及LVFS升高,LVESD和LVEDD明显下降(P<0.01)。旷场实验结果显示,与假手术组比较,复合模型组大鼠的水平运动得分和垂直运动得分均明显减少,活动能力下降(P<0.01);与复合模型组比较,中药组大鼠水平运动得分增加(P<0.05)。高架十字迷宫实验结果显示,复合模型组倾向于待在闭臂里,中药组大鼠更倾向于待在开臂里。病理染色结果显示:与假手术组和中药组比较,复合模型组心肌纤维化增多,尼氏小体数量明显减少。与假手术组比较,心肌梗死组及复合模型组外周血CRF、ACTH及CORT含量明显升高(P<0.05);与心肌梗死组比较,复合模型组外周血ACTH及CORT明显升高(P<0.01);与复合模型组比较,中药组外周血CRF、ACTH及CORT含量明显下降(P<0.05)。结论心肌梗死大鼠存在HPA轴亢进,且焦虑会加重心肌梗死大鼠HPA轴的紊乱;柴胡加龙骨牡蛎汤治疗心肌梗死合并焦虑可能与调控HPA轴有关。

Objective To explore the effect of Chaihu and Longgu Muli Decoction on hypothalamic-pituitary-adrenal(HPA)axis in rats with myocardial infarction complicated with anxiety.Methods Thirty six-week-old healthy male Sprague-Dawley(SD)rats without specific pathogen(SPF)were randomly divided into myocardial infarction group,compound model group(myocardial infarction model combined with anxiety model),traditional Chinese medicine(TCM)group(compound model+Chaihu and Longgu Muli Decoction)and the sham operation group.On the basis of compound model group,traditional Chinese medicine group was given Chaihu and Longgu Muli Decoction by gavage,and other groups were given distilled water by gavage.Left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular short axis rate(LVFS),and left ventricular ejection fraction(LVEF)were detected by echocardiography.Open field test and elevated cross maze were used to detect rat behavior.Masson staining and Nissl staining at the edge of myocardial infarction were observed by electron microscopy.The levels of adrenocorticotropin-releasing hormone(CRF),adrenocorticotropin(ACTH),and corticosterone(CORT)in peripheral blood of rats were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the sham operation group,the values of LVEF and LVFS in the myocardial infarction group and the compound model group were significantly decreased,and the values of LVESD and LVEDD were significantly increased(P<0.01).Compared with the compound model group,the values of LVEF and LVFS in the TCM group were increased,and the values of LVESD and LVEDD were decreased significantly(P<0.01).The results of open field test showed that compared with the sham operation group,the horizontal and vertical motor scores of the compound model group were significantly reduced,and the activity ability was decreased(P<0.01).Compared with compound model group,the horizontal exercise score of rats in TCM group was increased(P<0.05).The results of the elevated cross maze experiment showed that the compound model group tended to stay in the closed arm,the TCM group were more inclined to stay in the open arm.The results of pathological staining showed that compared with the sham operation group and the TCM group,the myocardial fibrosis in the compound model group was increased,and the number of Nissl bodies was significantly reduced.Compared with the sham operation,the contents of CRF,ACTH,and COTR in peripheral blood of myocardial infarction group and compound model group were significantly increased(P<0.05).Compared with the myocardial infarction group,the peripheral blood ACTH,and CORT of the compound model group were significantly increased(P<0.01).Compared with the compound model group,the contents of CRF,ACTH,and CORT in peripheral blood of TCM group were significantly decreased(P<0.05).Conclusion Hyperintensity of HPA axis exists in rats with myocardial infarction,and anxiety can aggravate the disorder of HPA axis in rats with myocardial infarction.Chaihu and Longgu Muli Decoction in the treatment of myocardial infarction complicated with anxiety may be related to the regulation of HPA axis.