环磷酰胺在野百合碱诱导大鼠肺动脉高压模型中的作用

目的 应用环磷酰胺(CTX)对野百合碱(MCT)诱导的大鼠肺动脉高压(PAH)模型进行干预,观察CTX在该模型中的疗效,并对其机制进行初步探讨.方法 建立MCT诱导的PAH模型,用CTX对模型进行预防干预和治疗干预,分别在建模2、4周,通过右心导管技术测量大鼠肺动脉平均压( mPAP),与模型组比较,判断干预是否有效；...

Effectiveness of Cyclophosphomide in Monocrotaline-induced Pulmonary Arterial Hypertension Model

Objective To evaluate the efficacy of cyclophosphamide（CTX） in monocrotaline（MCT）-induced pulmonary arterial hypertension（PAH） model and to investigate the possible mechanism.Methods Rats received MCT（60 mg/kg intraperitoneal injection,i.p.） once,CTX treatment groups were divided into prophylactic and remedial intervention.At the end of week 2 and week 4,compare the mean pulmonary arterial pressure（mPAP） and ＂R value＂ of the prophylactic treatment group or remedial treatment group with of 2-week model group or 4-week model group respectively;immunohistochemistry staining was used to determine the expression of tumor necrosis factor α（TNF-α） and interleukin 6（IL-6） in the rat lung tissues.Results Remedial CTX intervention can significantly reduce the mPAP（compared with the 4-week model group,P0.01）,but prophylactic group showed no tendency of mPAP-reduction.Using R value to assess the efficacy of the remedial group,we found the same results.The immunohistochemistry staining showed there were massive expressions of TNF-α and IL-6 in the lung tissues of model groups and decreased staining in remedial groups.Conclusions Inhibition of TNF-α and IL-6 with CTX in MCT-induced PAH model was resulted in a significant reduction of mPAP and thickness of small pulmonary arteries.Inflammation may play a key role in the pathogenesis of MCT-induced PAH model.CTX may be useful in the therapeutic intervention of connective tissue disease associated with PAH.