多西他赛对野百合碱诱导的大鼠肺动脉高压的治疗作用  

Treatment of Docetaxel on Pulmonary Arterial Hypertension Induced by Monocrotaline in Rats

作　　者：郑常龙[1] 陈天天 詹蔚[1] 邹勇[2] 邓凯 符永玫[1] ZHENG Chang-long;CHEN Tian-tian;ZHAN Wei;ZOU Yong;DENG Kai;FU Yong-mei(Department of Emergency,Guangzhou 510630,China;Department of Blood Transfusion,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China;Research Institute of Guangzhou Eighth People’s Hospital,Guangzhou Medical University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第三医院急诊科 [2]中山大学附属第三医院输血科,广东广州510630 [3]广州医科大学附属广州市第八人民医院研究所,广东广州510080

出　　处：《中山大学学报（医学版）》2018年第5期654-659,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金青年项目(81500287);广东省科技发展专项基金(2017A030310035);广东省自然科学基金(2016A030313357)

摘　　要：【目的】研究多西他赛对野百合碱诱导的大鼠肺动脉高压的作用及可能机制。【方法】50只雄性SD大鼠随机分为5组:正常对照组(control)、多西他赛组(control+DTX)、野百合碱组(MCT)、野百合碱+溶媒组(MCT+SOL)和野百合碱+多西他赛组(MCT+DTX)。后3组大鼠一次性腹腔注射野百合碱(60 mg/kg)建立肺动脉高压模型。野百合碱注射后第21天和第28天,经尾静脉注射多西他赛(5 mg/kg)或溶媒进行干预。多导生理记录仪测定大鼠右心血流动力学,计算右心室肥厚指数(RVHI);左肺病理切片行van Geison染色,光镜下观察肺内小动脉病理改变,并计算肺小动脉中膜厚度与血管直径比值。Western blotting检测右肺组织中p-PDGFR和PDGFR的表达水平。【结果】与control组相比,MCT和MCT+SOL组大鼠的RVSP、RVHI、肺小动脉中膜厚度与血管直径比值、p-PDGFR和PDGFR的表达均显著增加(P <0.05);与MCT+SOL组相比,MCT+DTX组RVSP、RVHI、肺小动脉中膜厚度与血管直径比值、p-PDGFR和PDGFR的表达均显著下降(P <0.05);Control+DTX组与control组相比,以上指标的差异均无显著性(P>0.05)。【结论】多西他赛可降低野百合碱诱导的大鼠肺动脉高压、减轻肺血管重构,其机制可能与抑制PDGFR的表达及其磷酸化有关。Abstract:【Objective】To investigate the effect and mechanism of docetaxel on pulmonary hypertension induced by monocrotaline in rats.【Methods】50 male SD rats were randomly divided into five groups:normal control group(con-trol),docetaxel group(control+DTX),monocrotaline group(MCT),monocrotaline+dissolvent group(MCT+SOL)and monocrotaline+docetaxel group(MCT+DTX).The rats in the later three groups were intraperitoneally injected with mono-crotaline(60 mg/kg)to establish the pulmonary hypertension model.Docetaxel(5 mg/kg)or solvent was respectively in-jected from the tail vein at the 21st day and 28th day after monocrotaline injection.The right ventricular systolic pressure(RVSP)and right ventricular hypertrophy index(RVHI)were measured.The left lung tissue slices were stained with van Geison staining.The morphological changes of pulmonary arterioles were observed,and the ratio of median thickness and vessel diameter of pulmonary arterioles was calculated.The expression of p-PDGFR and PDGFR in right lung tissues was detected by western blotting.【Results】RVSP,RVHI,the ratio of median thickness and vessel diameter of pulmonary ar-terioles and the lever of p-PDGFR and PDGFR in the MCT group and MCT+SOL group were significantly increased com-pared with those in the normal control group(P<0.05).Compared with the MCT+SOL group,these parameters of RVSP,RVHI,the ratio of median thickness and vessel diameter of pulmonary arterioles and the expression of p-PDGFR and PDGFR were significantly decreased in MCT+DTX group(P<0.05).There was no significant difference in the above parameters between control+DTX group and control group(P>0.05).【Conclusion】Docetaxel is capable of reducing pul-monary hypertension and reversing pulmonary vascular remodeling on pulmonary hypertension induced by monocrotaline in rats,which may be related to the inhibition of PDGFR expression and its phosphorylation.

关 键 词：肺动脉高压 野百合碱 多西他赛 血小板源性衍生因子受体 

分 类 号：R54[医药卫生—心血管疾病]