童心康合剂治疗小儿病毒性心肌炎理论及实验研究

发布时间：2018-03-24 23:07

本文选题：小儿病毒性心肌炎　切入点：解毒活血、益气养阴　出处：《山东中医药大学》2016年博士论文

【摘要】：目的:探讨童心康合剂治疗小儿病毒性心肌炎的理论依据及免疫机制。方法:基于中医传承辅助平台整理小儿病毒性心肌炎相关古代及现代文献,分析病因病机、治法方药研究概况,探讨毒瘀互结,气阴两虚的病因病机理论,提出解毒活血,益气养阴的治疗原则,研制成童心康合剂。采用注射猪心肌肌球蛋白免疫Lewis大鼠建立实验性自身免疫性心肌炎模型,予童心康合剂干预21天后,观察心肌病理变化,ELISA法检测血清心肌肌钙蛋白T、脑钠素、γ-干扰素、白介素-2、白介素-4、白介素-6水平,免疫组化法检测心肌白介素-2、白介素-2受体、信号转导及转录因子5的表达;药物干预56天后,Masson染色观察心肌纤维化,免疫组化法检测基质金属蛋白酶9和抑制因子1的表达。结果:提出毒瘀互结为小儿病毒性心肌炎发病之基础,气阴两伤为发病之关键,邪正消长变化致病情错综复杂;确立解毒活血、益气养阴的治则,据法研制童心康合剂。实验证实童心康合剂能显著改善免疫21天实验性自身免疫性心肌炎模型大鼠的体重下降、减轻心肌细胞的坏死和炎性浸润、降低反映心肌损伤的心肌肌钙蛋白T和心衰定量标志物脑钠素的水平,降低血清γ-干扰素、白介素-2水平,升高白介素-4、白介素-6水平,下调心肌组织白介素-2、白介素-2受体、信号转导及转录因子5的表达;对于免疫56天的实验性自身免疫性心肌炎模型大鼠有抗纤维化作用,上调心肌组织基质金属蛋白酶9的表达,下调其抑制因子1的表达。结论:本研究认为毒瘀互结,气阴两虚是小儿病毒性心肌炎的重要病机,提出了解毒活血,益气养阴的治疗原则。实验研究证实童心康合剂可以减轻实验性自身免疫性心肌炎模型大鼠的心肌炎症,通过降低Th1细胞分泌的γ-干扰素和白介素-2,提高Th2细胞分泌的白介素-4和白介素-6水平,调节实验性自身免疫性心肌炎模型大鼠出现的Th1/Th2失衡,并调节相关白介素-2/信号转导及转录因子5信号通路是其可能机制之一;上调心肌组织基质金属蛋白酶9的表达,下调抑制因子1的表达,发挥抗纤维化作用亦是其保护心肌的原因,为“解毒活血、益气养阴”这一新策略提供实验依据。
[Abstract]:Objective: to explore the theoretical basis and immune mechanism of Tongxinkang mixture in the treatment of viral myocarditis in children. The general situation of the research on the prescriptions of the treatment method, the discussion on the theory of the etiology and pathogenesis of the combination of toxin and stasis, the deficiency of qi and yin, and the treatment principle of detoxifying, activating blood circulation and nourishing qi and nourishing yin. Tongxinkang mixture was prepared. Experimental autoimmune myocarditis model was established in Lewis rats immunized with porcine cardiac myosin. The model was treated with Tongxinkang mixture for 21 days. Serum levels of cardiac troponin T, brain natriuretic peptide (BNP), interferon 纬 (IFN 纬), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6) were detected by Elisa, and myocardial interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R) were detected by immunohistochemistry. Signal transduction and expression of transcription factor 5, myocardial fibrosis were observed by Masson staining after 56 days of drug intervention. Results: the expression of matrix metalloproteinase 9 and inhibitor of matrix metalloproteinase 1 was detected by immunohistochemistry. Results: it was suggested that the combination of toxin and blood stasis was the basis of the pathogenesis of viral myocarditis in children, Qi and Yin injuries were the key to the development of viral myocarditis, and the changes of pathogenic factors were complicated. To establish the principle of detoxifying and promoting blood circulation and nourishing qi and nourishing yin, Tongxinkang mixture was developed according to the method. The experiment proved that Tongxinkang mixture can significantly improve the weight loss of experimental autoimmune myocarditis model rats after 21 days of immunization. The levels of cardiac troponin T and brain natriuretic peptide (BNP), a quantitative marker of heart failure, and the levels of serum interferon 纬 and interleukin-2 were decreased, and the levels of interleukin-4 and interleukin-6 were increased. Down-regulate the expression of interleukin-2, interleukin-2 receptor, signal transduction and transcription factor 5 in myocardial tissue, and have anti-fibrosis effect on experimental autoimmune myocarditis model rats immunized for 56 days. Conclusion: this study suggests that toxin and blood stasis and deficiency of qi and yin are the important pathogenesis of viral myocarditis in children. Experimental study shows that Tongxinkang mixture can reduce myocarditis in experimental autoimmune myocarditis model rats. By decreasing interferon 纬 and interleukin-2 secreted by Th1 cells, increasing the levels of interleukin-4 and interleukin-6 secreted by Th2 cells, regulating the imbalance of Th1/Th2 in experimental autoimmune myocarditis rats. Regulating the related interleukin-2 / signal transduction and transcription factor 5 signaling pathway is one of its possible mechanisms, and up-regulates the expression of matrix metalloproteinase-9 and down-regulates the expression of inhibitor of metalloproteinase-1. The anti-fibrosis effect is also the cause of myocardial protection, which provides experimental basis for the new strategy of "detoxification, promoting blood circulation, supplementing qi and nourishing yin".
【学位授予单位】：山东中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R272

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