EAMG大鼠胸腺、下丘脑-垂体-肾上腺皮质轴的病理变化及补脾强力复方的干预作用研究
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摘要
目的:探讨实验性自身免疫性重症肌无力(Experimental Autoimmune Myasthenia Gravis,EAMG)模型大鼠胸腺下丘脑-垂体-肾上腺皮质(HPA)轴的病理变化情况及补脾强力复方对其的干预作用。方法:SPF级雌性Lewis大鼠72只,随机分为正常组、模型组、强的松组及补脾强力复方大、中、小剂量组,每组各12只。对除正常组外的其余组大鼠制备EAMG模型。通过HE染色法观察EAMG大鼠胸腺、HPA轴的病理变化;药物干预后观察各组大鼠胸腺、HPA轴功能的差异。结果:与正常组相比,EAMG大鼠出现了胸腺细胞滤泡性增生,形成较多生发中心以及淋巴滤泡;肾上腺皮质变薄,束状带细胞萎缩,形成囊状空泡及腺瘤样改变;下丘脑神经细胞有不同程度的细胞变性,出现胶质细胞增生、细胞核固缩或消失,形成空泡;垂体神经细胞嗜酸性细胞呈弥漫性或结节性增生,偶见腺瘤样变。与各相应模型组对比,补脾强力复方组EAMG大鼠的胸腺、HPA轴的病理变化范围及程度减轻。结论:EAMG大鼠的胸腺、肾上腺、下丘脑、垂体可见病理性变化,而具有补脾益肾、温扶阳气作用的补脾强力复方对上述病理变化有一定的干预作用,其中在保护EAMG大鼠肾上腺形态功能上的作用较优。
Objective: To investigate the pathological changes of the thymus and the hypothalamic-pituitary-adrenocortical(HPA) axis in rats with experimental autoimmune myasthenia gravis(EAMG) and the interventional effect of compound spleen-tonifying prescription. Methods: A total of 72 specific pathogen-free female Lewis rats were randomly divided into normal group,model group,prednisone group,and high-,medium-,and low-dose compound spleen-tonifying prescription groups,with 12 rats in each group. All rats except those in the normal group were used to establish a model of EAMG. HE staining was used to observe the pathological changes of the thymus and the HPA axis; the functions of the thymus and the HPA axis were compared between groups after drug intervention. Results: Compared with the normal rats,the EAMG rats had follicular hyperplasia of thymocytes,the formation of more germinal centers and lymphoid follicles;the adrenal cortexbecame thinner,and showed atrophy of fascicular cells,with the formation of cystic vacuoles and adenomatoid changes; the hypothalamic neurons showedvarying degrees of cell degeneration,with glial cell proliferation,karyopyknosis or disappearance of nuclei,and the formation of vacuoles; pituitary eosinophils showed diffuse or nodular hyperplasia,with occasional adenomatoid changes. Compared with the model group,the compound spleen-tonifying prescription groups had significant reductions in the extent and degree of the pathological changes of the thymus and the HPA axis. Conclusion: EAMG rats have visible pathological changes of the thymus,the adrenal gland,the hypothalamus,and the pituitary gland. Compound spleen-tonifying prescription has spleen-tonifying,kidney-nourishing,and yang-supporting effects and thus exerts a certain interventional effect on these pathological changes,especially a better effect in protecting the morphology and function of the adrenal gland in EAMG rats.
Objective: To investigate the pathological changes of the thymus and the hypothalamic-pituitary-adrenocortical(HPA) axis in rats with experimental autoimmune myasthenia gravis(EAMG) and the interventional effect of compound spleen-tonifying prescription. Methods: A total of 72 specific pathogen-free female Lewis rats were randomly divided into normal group,model group,prednisone group,and high-,medium-,and low-dose compound spleen-tonifying prescription groups,with 12 rats in each group. All rats except those in the normal group were used to establish a model of EAMG. HE staining was used to observe the pathological changes of the thymus and the HPA axis; the functions of the thymus and the HPA axis were compared between groups after drug intervention. Results: Compared with the normal rats,the EAMG rats had follicular hyperplasia of thymocytes,the formation of more germinal centers and lymphoid follicles;the adrenal cortexbecame thinner,and showed atrophy of fascicular cells,with the formation of cystic vacuoles and adenomatoid changes; the hypothalamic neurons showedvarying degrees of cell degeneration,with glial cell proliferation,karyopyknosis or disappearance of nuclei,and the formation of vacuoles; pituitary eosinophils showed diffuse or nodular hyperplasia,with occasional adenomatoid changes. Compared with the model group,the compound spleen-tonifying prescription groups had significant reductions in the extent and degree of the pathological changes of the thymus and the HPA axis. Conclusion: EAMG rats have visible pathological changes of the thymus,the adrenal gland,the hypothalamus,and the pituitary gland. Compound spleen-tonifying prescription has spleen-tonifying,kidney-nourishing,and yang-supporting effects and thus exerts a certain interventional effect on these pathological changes,especially a better effect in protecting the morphology and function of the adrenal gland in EAMG rats.
引文
[1]晏琳,罗梦川,杨欢.重症肌无力的免疫机制研究进展[J].中国神经免疫学和神经病学杂志,2012,19(6):419-423.
[2]梁燕,邱少波,刘萍.重症肌无力的中医治疗研究进展[J].湖北中医药大学学报,2012,14(3):71-73.
[3]黄志,田增春.重症肌无力免疫学及相关发病机制研究进展[J].重庆医学,2010,39(9):1144-1147.
[4]王卫,魏东宁.胸腺瘤相关重症肌无力发病的免疫学机制研究进展[J].解放军医学杂志,2013,38(7):606-610.
[5]张慜,李军朝,李柱一.胸腺异常免疫反应在重症肌无力发病机制中的研究进展[J].中国神经免疫学和神经病学杂志,2013,20(5):360-362.
[6]高峰.胸腺与重症肌无力[J].郑州大学学报:医学版,2005,40(1):1-4.
[7]Tomiyam N,Miller,Ellis J,et al.Invasive and noninvasive thymoma:distinctive CT features[J].J Comput Assist Tomogr,2001,25(3):388-393.
[8]马书娟,姚建平,樊蔚虹,等.柴胡疏肝散对抑郁症模型大鼠HPA轴功能的影响[J].中国中医基础医学杂志,2014,20(9):1210.
[9]赖娟,况时祥.补脾强力复方治疗重症肌无力Ⅰ、Ⅱ型患者的临床研究[A].贵州省第六届中西医结合神经科学术年会论文汇编[C].2013.
[10]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004(9):1069-1072.
[11]Baggi F,Annoni A,Ubiali F,et al.Breakdown of tolerance to a self-peptide of acetylcholine receptora-subunit induces experimental myasthenia gravis in rats[J].J of immunology,2004(172):2697-2703.
[12]许文华,韩莹莹,汪思应,等.鼠源乙酞胆碱受体Q亚基97-116肤段免疫e Liws鼠诱导实验性重症肌无力模型[J].中国神经精神疾病杂志,2006(32):179-180.
[13]Kondo K,Monden Y.Therapy for thymic epithelial tumors:a clinical study of 1,320 patients from Japan[J].The Annals of thoracic surgery,2003,76(3):878-884.
[14]Kohman LJ.Controversies in the management of malignant thymoma[J].CHEST Journal,1997,112(4):296-300.
[15]王乃峰.重症肌无力患者的胸腺病理变化的临床意义分析[J].中国现代药物应用,2011,5(2):81-82.
[16]Nagane Y,Utsugisawa K,Obara D,et al.Dendritic cells in hyperplastic thymuses from patients with myasthenia gravis[J].Muscle nerve,2003,27(5):582-589.
[17]Nieto IP,Robledo JPP,Pajuelo MC,et al.Prognostic factors for myasthenia gravis treated by thymectomy:review of 61 cases[J].The Annals of thoracic surgery,1999,67(6):1568-1571.
[18]Iyer A,Elsone L,Appleton R,et al.A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica[J].Autoimmunity,2014(47):154-161.
[19]Sandri A,Cusumano G,Lococo F,et al.Long-term results after treatment for recurrent thymoma:a multicenter analysis[J].J Thorac Oncol,2014,9(12):1796-1804.
[20]王静,周双秀,况时祥.补脾强力复方对重症肌无力胸腺切除术前后干预的临床研究[J].时珍国医国药,2016,27(2):383-385.
[21]姜雄,何前松,况时祥.补脾强力复方对自身免疫性重症肌无力大鼠胸腺组织GR mRNA表达的影响[J].辽宁中医杂志,2017,44(2):398-401.
[22]王静,况时祥.免疫系统与HPA轴相关性的研究进展[J].湖北中医药大学学报,2017,19(2):110-113.
[23]闾倩,汤玮,梁翠,等.糖皮质激素冲击治疗甲状腺相关性眼病对肾上腺皮质功能的影响[J].上海医学,2013,36(5):425-428.
[24]余增才,陈洁君,麦颖琦,等.基于H-E染色和免疫组化技术探讨激素类药物对正常SD大鼠下丘脑-垂体-肾上腺轴的影响[J].今日药学,2015,25(11):753-757.
[25]宋春风,郑师陵,吕佩源,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴、血淋巴细胞Ca2+和血清钙的影响[J].中国中医基础医学杂志,2002,8(5):354-356.
[26]赵荣华,刘进娜,李聪,等.肝郁、脾虚和肝郁脾虚证模型大鼠下丘脑-垂体-肾上腺轴变化及柴疏四君汤的干预效应[J].中国中西医结合杂志,2015,35(7):834-838.
[27]刘继刚.况时祥教授补脾益肾法治疗重症肌无力经验[J].四川中医,2007,25(9):7-8.
[2]梁燕,邱少波,刘萍.重症肌无力的中医治疗研究进展[J].湖北中医药大学学报,2012,14(3):71-73.
[3]黄志,田增春.重症肌无力免疫学及相关发病机制研究进展[J].重庆医学,2010,39(9):1144-1147.
[4]王卫,魏东宁.胸腺瘤相关重症肌无力发病的免疫学机制研究进展[J].解放军医学杂志,2013,38(7):606-610.
[5]张慜,李军朝,李柱一.胸腺异常免疫反应在重症肌无力发病机制中的研究进展[J].中国神经免疫学和神经病学杂志,2013,20(5):360-362.
[6]高峰.胸腺与重症肌无力[J].郑州大学学报:医学版,2005,40(1):1-4.
[7]Tomiyam N,Miller,Ellis J,et al.Invasive and noninvasive thymoma:distinctive CT features[J].J Comput Assist Tomogr,2001,25(3):388-393.
[8]马书娟,姚建平,樊蔚虹,等.柴胡疏肝散对抑郁症模型大鼠HPA轴功能的影响[J].中国中医基础医学杂志,2014,20(9):1210.
[9]赖娟,况时祥.补脾强力复方治疗重症肌无力Ⅰ、Ⅱ型患者的临床研究[A].贵州省第六届中西医结合神经科学术年会论文汇编[C].2013.
[10]黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004(9):1069-1072.
[11]Baggi F,Annoni A,Ubiali F,et al.Breakdown of tolerance to a self-peptide of acetylcholine receptora-subunit induces experimental myasthenia gravis in rats[J].J of immunology,2004(172):2697-2703.
[12]许文华,韩莹莹,汪思应,等.鼠源乙酞胆碱受体Q亚基97-116肤段免疫e Liws鼠诱导实验性重症肌无力模型[J].中国神经精神疾病杂志,2006(32):179-180.
[13]Kondo K,Monden Y.Therapy for thymic epithelial tumors:a clinical study of 1,320 patients from Japan[J].The Annals of thoracic surgery,2003,76(3):878-884.
[14]Kohman LJ.Controversies in the management of malignant thymoma[J].CHEST Journal,1997,112(4):296-300.
[15]王乃峰.重症肌无力患者的胸腺病理变化的临床意义分析[J].中国现代药物应用,2011,5(2):81-82.
[16]Nagane Y,Utsugisawa K,Obara D,et al.Dendritic cells in hyperplastic thymuses from patients with myasthenia gravis[J].Muscle nerve,2003,27(5):582-589.
[17]Nieto IP,Robledo JPP,Pajuelo MC,et al.Prognostic factors for myasthenia gravis treated by thymectomy:review of 61 cases[J].The Annals of thoracic surgery,1999,67(6):1568-1571.
[18]Iyer A,Elsone L,Appleton R,et al.A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica[J].Autoimmunity,2014(47):154-161.
[19]Sandri A,Cusumano G,Lococo F,et al.Long-term results after treatment for recurrent thymoma:a multicenter analysis[J].J Thorac Oncol,2014,9(12):1796-1804.
[20]王静,周双秀,况时祥.补脾强力复方对重症肌无力胸腺切除术前后干预的临床研究[J].时珍国医国药,2016,27(2):383-385.
[21]姜雄,何前松,况时祥.补脾强力复方对自身免疫性重症肌无力大鼠胸腺组织GR mRNA表达的影响[J].辽宁中医杂志,2017,44(2):398-401.
[22]王静,况时祥.免疫系统与HPA轴相关性的研究进展[J].湖北中医药大学学报,2017,19(2):110-113.
[23]闾倩,汤玮,梁翠,等.糖皮质激素冲击治疗甲状腺相关性眼病对肾上腺皮质功能的影响[J].上海医学,2013,36(5):425-428.
[24]余增才,陈洁君,麦颖琦,等.基于H-E染色和免疫组化技术探讨激素类药物对正常SD大鼠下丘脑-垂体-肾上腺轴的影响[J].今日药学,2015,25(11):753-757.
[25]宋春风,郑师陵,吕佩源,等.补肾中药对肾阳虚大鼠下丘脑-垂体-肾上腺轴、血淋巴细胞Ca2+和血清钙的影响[J].中国中医基础医学杂志,2002,8(5):354-356.
[26]赵荣华,刘进娜,李聪,等.肝郁、脾虚和肝郁脾虚证模型大鼠下丘脑-垂体-肾上腺轴变化及柴疏四君汤的干预效应[J].中国中西医结合杂志,2015,35(7):834-838.
[27]刘继刚.况时祥教授补脾益肾法治疗重症肌无力经验[J].四川中医,2007,25(9):7-8.