摘要
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;通过肺脏病理组织苏木精-伊红(HE)染色进行肺小动脉血管壁增厚定量测定(R值);免疫组化染色测定炎症因子肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的表达量,探讨CTX的干预机制。结果 CTX预防组mPAP为(30.07±5.96)mmHg(1mmHg=0.133kPa),与2周模型组(28.67±8.17)mmHg相比无明显差异;CTX治疗组mPAP为(24.15±4.62)mmHg,与4周模型组(66.17±28.05)mmHg相比显著降低(P<0.01)。肺脏病理组织HE染色显示CTX治疗组测定R值(0.227±0.034)与4周模型组(0.124±0.009)相比显著增高(P<0.01),提示肺小血管壁厚度显著降低;免疫组化染色显示野百合碱模型大鼠肺组织中有大量炎性细胞浸润,并有大量TNF-α和IL-6的表达,CTX治疗组较4周模型组TNF-α和IL-6染色减少。结论 CTX对MCT诱导的大鼠PAH模型有治疗作用,其机制与抑制肺小动脉血管炎症和血管壁增厚相关。
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.
出处
《中华临床免疫和变态反应杂志》
2011年第4期272-277,I0002,I0003,共8页
Chinese Journal of Allergy & Clinical Immunology
基金
国家"十一五"科技支撑计划课题(2006BAI01A07和2008BAI59B02)
中华医学会临床医学科研专项资金项目(08010270105)
关键词
肺动脉高压
野百合碱
环磷酰胺
炎症因子
pulmonary arterial hypertension
monocrotaline
cyclophosphomide
inflammatory factors
