麻黄细辛附子汤对肾阳虚外感小鼠及正常小鼠的效-毒作用研究

Efficacy-toxicity Evaluation of Mahuang Xixin Fuzi Decoction on Mice with Kidney-yang Deficiency

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。

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-γin 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-αand 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.