目的 研究麻黄细辛附子汤(MXF)干预肾阳虚外感小鼠的药效作用及其对正常小鼠的毒性作用差异,并考察其效-毒作用机制。方法 BABL/C雄性小鼠随机分为正常组、正常毒性低、中、高剂量组;肾阳虚外感模型组;肾阳虚外感低、中、高剂量组,连续灌胃给药6 d,记录体重、肛温等药理指标并观察小鼠的一般体征,检测生化指标、炎症因子。结果 药效实验中,与正常组小鼠相比,肾阳虚外感模型组小鼠生化指标肌酸激酶(CK)、肌酸激酶-同工酶(CK-MB)、羟丁酸脱氢酶(α-HBDH)、乳酸盐脱氢酶(LDH)、丙氨酸氨基转移酶(ALT)、天冬氨酸转移酶(AST)、碱性磷酸酶(ALP)、尿素(urea)含量明显升高(P<0.05),炎症因子白介素-6(IL-6)、单核细胞去化蛋白(MCP-1)、肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10)、干扰素-γ(INF-γ)以及白介素12(IL-12p70)含量升高明显(P<0.05)。经给药治疗后,各给药组CK、ALT、urea等生化指标含量较模型组有所回调,各给药组IL-6、IL-10、IFN-γ等炎症因子含量较模型组有不同程度的回调;毒性研究中,各给药组生化指标CK、urea、半胱氨酸(CYS-C)的含量较正常组显著升高(P<0.05),炎症因子白介素-10(IL-10)含量明显上升、白介素-12(IL-12p70)含量明显下降(P<0.05)。结论 经MXF给药治疗后,肾阳虚外感给药组小鼠的一些生化指标均有不同程度的回调,MXF可通过调节IL-6、IL-10、IFN-γ、MCP-1、肿瘤坏死因子-α(TNF-α)等炎症因子改善机体的炎症反应;而正常小鼠给予不同剂量的MXF后心脏、肝脏和肾脏功能出现失调,机体通过细胞转移、打破免疫应答的平衡,从而使正常小鼠出现炎症反应。
Abstract
OBJECTIVE To study the pharmacodynamic effects of Mahuang Xixin Fuzi Decoction (MXF) on mice with kidney-yang deficiency, its toxic effects on normal mice and effect-toxic mechanism. METHODS BABL/C male mice were randomly divided into normal groups; normal groups with low, medium and high toxicity; kidney Yang deficiency model group. The low, medium and high dose groups were treated with infected Influenza virus of kidney-yang deficiency. After continuous gavage for 6 days, the body weight anal temperature and other pharmacological indicators were recorded, and the general signs, biochemical indicators and inflammatory factors of the mice were detected. RESULTS Compared with the normal group, the biochemical parameters of the kidney yang deficiency model group, which means the creatine kinase (CK), creatine kinase-isoenzyme (CK-MB), alpha-hydroxybutyrate dehydrogenase (α-HBDH), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP) and urea (urea) were significantly increased (P<0.05), inflammatory factors interleukin-6 (IL-6), monocyte deproteinization protein (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-10 (IL- 10), interferon-γ (INF-γ) and interleukin 12 (IL-12p70) increased significantly (P<0.05). After administration, the levels of biochemical markers such as CK, ALT and urea in each administration groups were slightly reduced compared with the model group. The levels of inflammatory factors such as IL-6, IL-10 and IFN-γ in each administration groups showed different degrees of callback compared with the model group. In the toxicity study, the biochemical indicators of CK, urea, and cysteine (CYS-C) in each drug-administered group were significantly higher than those in the normal group (P<0.05), and the inflammatory factor interleukin-10 (IL-10) increased significantly, and the content of interleukin-12 (IL-12p70) decreased significantly (P<0.05). CONCLUSION After treatment with MXF, the above biochemical indicators of mice with kidney yang deficiency and external sensation have different degrees of callback. MXF can achieve therapeutic effects by regulating IL-6, IL-10, IFN-γ, MCP-1, TNF-α and other factors on the body′s inflammatory response. While normal mice give different doses of MXF, the heart, liver and kidney function are dysfunctional, the balance of immune response of the body are broken through cell transfer, thus making normal mouse developed an inflammatory response.
关键词
麻黄细辛附子汤 /
效-毒关系 /
肾阳虚外感小鼠 /
生化指标 /
炎症因子
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Key words
Mahuang Xixin Fuzi decoction /
effect-toxic relationship /
mouse model of external sense of kidney yang deficiency /
biochemical index /
inflammatory factor
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中图分类号：
R965
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参考文献
[1] QIAN C C. Explanation of the version of “Treatise on Febrile Diseases”[J]. J Tradit Chin Med(中医文献杂志), 2011, 29 (5):1-4.
[2] TANG Z X, XU B H, HUANG Y Q, et al. Clinical dialectical application of Mahuang Xixin Fuzi Decoction[J]. Henan J Tradit Chin Med(河南中医), 1984, (3):24-26.
[3] LIU C H, QI Y F, HOU Y Y. Research progress of Mahuang Fuzi Xixin Decoction[J]. Shandong J Tradit Chin Med(山东中医杂志), 2016, 35(3):270-273.
[4] QIU D Y. Inhibition of β-asarone on synaptic transmission of airway parasympathetic preganglionic motor neurons [D]. Shanghai:Fudan University, 2012.
[5] ZHAO S F. The theory of "Xi Xin but money" ancient and modern[J]. Shaanxi J Tradit Chin Med(陕西中医), 2009, 30 (3):339-341.
[6] DONG X Y, ZHOU Y X, YOU W, et al. Effects of long-term toxicity of Asarum powder on liver and kidney function in SD rats[J]. Guangming J Tradit Chin Med(光明中医), 2015, 30 (12):2550-2552.
[7] WANG W, HUANG W, SUN R. Advances in research on chemical constituents of asarum based on efficacy and toxicity[J]. Chin J Pharmacov(中国药物警戒), 2013, 10 (1):36-38.
[8] YU C L, XU T J, ZHANG X J, et al. Study on the mechanism of toxicity difference between normal and blood stasis syndrome mice based on "definitely innocent" sputum[J]. Acta Pharm Sin(药学学报), 2019,54(2):329-334.
[9] PANG J Y, BAI Z F, NIU M, et al. Comparative study on the toxicity and protective effect of Polygonum multiflorum Thunb. on normal and liver injury rats based on "definitely innocent"[J]. Acta Pharm Sin(药学学报), 2015, 50 (8):973-979.
[10] LIUY B, QIN J J, YANGS H,et al. Analysis of the effect of crude yellow water extract on atherosclerosis based on "il-34"-rock signal pathway[J]. Chin Pharm J(中国药学杂志),2019,54(8):624-631.
[11] CHEN S H, LV G Y, FAN J, et al. Effects of different extracts of hippocampus on estradiol-induced kidney-yang deficiency mice[J]. Chin Tradit Herb Drugs(中草药), 2009, 40(2):258-262.
[12] YANG Y. Establishment of a mouse model of kidney yang deficiency and intervention of Mahuang Xixin Fuzi Decoction [D]. Jinan:Shandong University of Traditional Chinese Medicine, 2012.
[13] LI C, SUN Q H, FU Y P, et al. Mechanism of intervention of Mahuang Xixin Fuzi Decoction on mice infected with H1N1 influenza virus based on fecal metabolites[J]. Chin J Exp Tradit Med Form(中国实验方剂学杂志), 2017, 23(9):74-79.
[14] MIAO P, LU M S, ZHANG D Q. Recent advances in the association between IL-6/IL-6 receptor and rheumatoid arthritis[J]. Immunol J (免疫学杂志), 2011, 27(4):355-360.
[15] HUANG A X, LU L W, LIU W J, et al. Plasma inflammatory cytokine IL-4, IL-8, IL-10, and TNF-α levels correlate with pulmonary function in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome[J]. Med Sci Monit, 2016, 22:2800-2808.
[16] LI S W, LI X T, ZHOU J H, et al. Experimental study on the prevention of intestinal adhesion after abdominal surgery in rats with interferon gamma[J]. Chin J Bas Clin Gen Surg(中国普外基础与临床杂志), 2019, 26(1):19-24.
[17] XIA L Y, LIU W J, LI M X, et al. Effects of Kudoutangchao recipe on ICAM-1, INF-γ and MCP-1 in rats with immunoprostatitis[J]. China J Chin Mater Med(中国中药杂志), 2014, 39(10):1918-1920.
[18] ZHAI B W, LI M H, PEI P P, et al. Effects of Shegan Mahuang Decoction on airway inflammation and serum IL-6 and IL-10 levels in asthmatic mouse models[J]. J Emerg Tradit Chin Med(中国中医急症), 2017, 26(5):783-785,822.
[19] QIAO H M, PANG H X, ZHANG Y F, et al. Changes of IL-6, IL-10 and TNF-α in children with mycoplasma pneumoniae[J]. J Clin Pediatr(临床儿科杂志), 2012, 30 (1):59-61.
[20] WANG Y C, SHI T X, LI M, et al. Determination of serum IL-6, IL-12P70 and β-endorphin and histamine in patients with chronic idiopathic urticaria[J]. Chin J Lepr Skin Dis(中国麻风皮肤病杂志), 2010, 26 (2):89-91.
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脚注
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基金
国家自然科学基金项目资助(81774167,81873220);山东省重点研发计划资助(2018CXGC1307)
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