醒脾解郁方对CUMS抑郁模型大鼠血清IL-8及肝脏MDA、mtDNA、ATP含量水平的影响
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摘要
目的从炎症、氧化应激、能量代谢三个角度研究抑郁症中医病机演变规律的生物学实质及醒脾解郁方的作用机理,以动态探究中医药防治抑郁症不同阶段的原则与方法。方法将48只Wistar大鼠随机分为空白对照组、模型组、中药组、西药组(舍曲林)各12只,采用6周慢性不可预见性温和应激(CUMS)方法建立抑郁大鼠模型,应激同时灌胃给药,于2、6周末分别采集各组血清及肝脏组织,检测血清白介素-8 (interleukin-8,IL-8)含量、肝脏丙二醛(malondialdehyde, MDA)含量、肝细胞线粒体DNA(mitochondrial DNA,mtDNA)含量及肝组织腺嘌呤核苷三磷酸(adenosine triphosphate,ATP)含量。结果应激2周时,IL-8含量升高(P<0.05);应激6周时,IL-8含量进一步升高(P<0. 01),MDA含量升高(P<0. 05),mtDNA含量显著降低(P<0. 01),ATP含量降低(P<0. 05)。盐酸舍曲林及中药醒脾解郁方对上述指标变化具有拮抗作用。结论 CUMS大鼠应激过程中可先后出现炎症反应、氧化应激反应、线粒体功能障碍的病理变化,盐酸舍曲林及中药醒脾解郁方均可抑制炎症及氧化应激反应,改善线粒体功能。两者相比,盐酸舍曲林在改善肝细胞mt DNA方面更有优势,而醒脾解郁方在提高肝脏ATP含量方面更有优势。
Objective To study the biological essence of the changes of pathological mechanism of depression in Chinese medicine and the mechanism of the Chinese prescription from three levels of inflammation, oxidative stress and energy metabolism, so as to explore the principles and methods of preventing and controlling the different stages of depression by Chinese medicine. Methods A total of 48 Wistar rats were randomly divided into the blank control group, the model group, the Chinese medicine group, and the Western medicine group(sertraline), with 12 rats in each group. 6 weeks of Chronic Unpredictability and Mild Stress(CUMS) method was used to establish the model of depressive rats, and the rats were given drugs at the same time. The serum and liver tissues were collected at the end of the 2 and 6 weeks. The levels of Interleukin-8(IL-8) in serum and Malondialdehyde(MDA), Mitochondrial DNA( mtDNA), Adenosine triphosphate( ATP) of liver cell were detected. Results The content of IL-8 increased(P<0. 05) when rats were suffered from 2-week CUMS; Meanwhile, the content of IL-8 was further increased(P<0.01), MDA content increased(P<0.05), mtDNA content decreased significantly(P<0. 01), ATP content decreased(P<0. 05) when rats were suffered from 6-week CUMS. Sertraline hydrochloride and Chinese medicine compound formula Xingpi Jieyu Granule had an antagonistic effect on the above indexes. Conclusion Pathological changes of inflammation, oxidative stress and mitochondrial dysfunction may occur successively during stress in CUMS rats. Sertraline hydrochloride and Xingpi Jieyu Granule can inhibit inflammation and oxidative stress and improve mitochondrial function. Sertraline hydrochloride has more advantages in improving mtDNA of hepatocytes, while Xingpi Jieyu Granule has more advantages in increasing ATP content of liver.
Objective To study the biological essence of the changes of pathological mechanism of depression in Chinese medicine and the mechanism of the Chinese prescription from three levels of inflammation, oxidative stress and energy metabolism, so as to explore the principles and methods of preventing and controlling the different stages of depression by Chinese medicine. Methods A total of 48 Wistar rats were randomly divided into the blank control group, the model group, the Chinese medicine group, and the Western medicine group(sertraline), with 12 rats in each group. 6 weeks of Chronic Unpredictability and Mild Stress(CUMS) method was used to establish the model of depressive rats, and the rats were given drugs at the same time. The serum and liver tissues were collected at the end of the 2 and 6 weeks. The levels of Interleukin-8(IL-8) in serum and Malondialdehyde(MDA), Mitochondrial DNA( mtDNA), Adenosine triphosphate( ATP) of liver cell were detected. Results The content of IL-8 increased(P<0. 05) when rats were suffered from 2-week CUMS; Meanwhile, the content of IL-8 was further increased(P<0.01), MDA content increased(P<0.05), mtDNA content decreased significantly(P<0. 01), ATP content decreased(P<0. 05) when rats were suffered from 6-week CUMS. Sertraline hydrochloride and Chinese medicine compound formula Xingpi Jieyu Granule had an antagonistic effect on the above indexes. Conclusion Pathological changes of inflammation, oxidative stress and mitochondrial dysfunction may occur successively during stress in CUMS rats. Sertraline hydrochloride and Xingpi Jieyu Granule can inhibit inflammation and oxidative stress and improve mitochondrial function. Sertraline hydrochloride has more advantages in improving mtDNA of hepatocytes, while Xingpi Jieyu Granule has more advantages in increasing ATP content of liver.
引文
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[3]王椿野,郭蓉娟.肝郁化火证的研究进展[J].环球中医药,2012,5(2):138-142.
[4]陈家旭,杨维益,梁嵘.肝气虚证临床证型的病理生理学初步研究[J].中国中西医结合杂志,1995,14(2):67-70.
[5]彭云丽.慢性应激诱发抑郁行为的炎性机制研究[D].上海:第二军医大学,2013.
[6]顾宇彤.慢性阻塞性肺病氧化抗氧化失衡与炎症反应关系的研究[D].上海:复旦大学,2005.
[7]张素素,孙嘉.线粒体DNA拷贝数的研究新进展[J].医学综述,2014,20(24):4417-4419.
[8]龚晴丽,李雪,鲁严.氧化应激相关性疾病中线粒体机制的研究进展[J].中国细胞生物学学报,2013,35(10):1540-1545.
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