摘要
目的观察喘可治注射液(CKZ)对慢性阻塞性肺疾病(COPD)大鼠肺组织IL-12/IL-12R/STAT4信号通路的影响。方法 50只SD大鼠随机分为正常组,模型组,CKZ高、中、低剂量(CKZ-H、CHZ-M、CKZ-L)组。除正常组外,各组复制COPD大鼠模型,并给予相应药物治疗,观察CKZ对COPD大鼠血清和肺泡灌洗液(BALF)中γ-干扰素(IFN-γ)、白细胞介素12(IL-12)、白细胞介素12受体(IL-12R)以及肺组织信号转导子和转录激活子4(STAT4)m RNA表达的影响。结果喘可治注射液各剂量组肺组织病理形态均有不同程度的改善,且降低COPD大鼠血清和BALF中IFN-γ、IL-12、IL-12R(除CKZ-L组BALF中IL-12R外)水平(P<0.05,P<0.01),可抑制大鼠肺组织STAT4 m RNA的表达(P<0.01,P<0.05)。结论喘可治注射液能一定程度改善COPD大鼠肺组织病理损害,其作用机制可能与其抑制IFN-γ、IL-12、IL-12R表达,干扰IL-12/IL-12R/STAT4信号通路对靶基因的激活,下调STAT4 m RNA表达,进而调节Th1/Th2分化失衡有关。
Objective To observe the effects of Chuankezhi injection（CI）on IL-12/IL-12R/STAT4 signal pathway in the pulmonary tissue of chronic obstructive pulmonary disease（COPD）rats. Methods Fifty SD rats were randomized into 5 groups, i.e., normal group, model group, and high-, medium- and low-dose CI groups. COPD rat model was established, and then were given various concentrations of CI. The effects of CI on serum and bronchoalveolar lavage fluid（BALF） interferon gamma（IFN-γ）,IL-12 and IL-12R,and pulmonary mRNA expression of signal transducer and activator of transcription 4（STAT4）in COPD rats were observed. Results The pathological morphology of lung tissues was improved to different degrees in CI groups. High-, medium- and low-dose CI could decrease the serum and BALF levels of IFN-γ, IL-12 and IL-12R（P〈0.05, P〈 0.01）, and inhibit the mRNA expression of STAT4 in lung tissues of COPD rats （P 〈 0.01 or P 〈 0.05）. Conclusion CI can improve lung tissue pathological damage of COPD rats to certain degree. Its therapeutic mechanism may be associated with the inhibiting IFN-γ, IL-12,IL-12R expression,and interfering the activation ability of IL-12/IL-12R/STAT4 signaling pathway on target genes,down-regulating the mRNA expression of STAT4,and then adjusting the imbalance of Th1/Th2 differentiation.
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2015年第1期44-48,共5页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
广东省科技计划项目(2012B031800268)
广东省中医药局科研项目(20121215)
