补肺益肾组分方Ⅲ对大鼠实验性肺动脉高压的改善作用  

Improvement effect of Bufei Yishen prescriptionⅢon experimental pulmonary hepertension of rats

作　　者：任周新[1,2] 余海滨[1] 梅晓峰[1] 董浩然[1,2] 沈俊岭[3] 李建生[1,2] REN Zhouxin;YU Haibin;MEI Xiaofeng;DONG Haoran;SHEN Junling;LI Jiansheng(Department of Pharmacology,Collaborative Innovation Center for Chinese Medicine and Respiratory Disease Co-constructed by Henan Province and Education Ministry,Henan University of Chinese Medicine,Zhengzhou 450046,China;Academy of Chinese Medicine,Henan University of Chinese Medicine,Zhengzhou 450046,China;Key Laboratory of Viral Diseases Prevention and Treatment of Traditional Chinese Medicine,Henan Province,First Affiliated Hospital,Henan University of Chinese Medicine,Zhengzhou 450000,China.)

机构地区：[1]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心药理平台,河南郑州450046 [2]河南中医药大学中医药科学院,河南郑州450046 [3]河南中医药大学第一附属医院,河南省病毒性疾病中医药防治重点实验室,河南郑州450000

出　　处：《吉林大学学报（医学版）》2023年第2期280-288,共9页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(81973822);国家中医临床研究基地业务建设第二批科研专项项目(JDZX2015l56)。

摘　　要：目的:探讨补肺益肾组分方Ⅲ(ECC-BYPⅢ)对烟雾和细菌诱导的大鼠肺动脉高压(PH)的改善作用,初步阐明其作用机制。方法:SPF级SD大鼠随机分为对照组(n=9)和造模组(n=140)。对照组大鼠常规饲养,造模组大鼠给予香烟烟雾和克雷伯杆菌(Kp),制备PH模型。停止造模后,造模大鼠按照肺功能均匀的原则分为模型组(n=10)和低剂量(3.24 mg·kg^(-1)·d^(-1),n=9)、中剂量(6.48 mg·kg^(-1)·d^(-1),n=10)及高剂量(12.96 mg·kg^(-1)·d^(-1),n=10)ECC-BYPⅢ组。给药大鼠按照组别每天分别给予相应剂量的ECC-BYPⅢ灌胃,对照组和模型组大鼠给予等量生理盐水灌胃。连续给药4周。第29天检测各组大鼠肺动脉平均压(mPAP)、收缩压(PASP)、舒张压(PADP)和右心肥大指数(RVHI)。取大鼠肺组织,部分采用苏木精-伊红(HE)染色,观察各组大鼠肺组织中肺小动脉周围炎症等病变;部分采用维多利亚蓝染色,测定各组大鼠肺小动脉血管中非肌性血管、部分肌性血管和肌性血管的百分比,肺小动脉管壁厚度占管径的百分比(WT%)及血管腔面积占血管总面积百分比(LA%)。另取大鼠肺组织,采用酶联免疫吸附试验(ELISA)法检测各组大鼠肺组织中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、内皮素1(ET-1)和前列环素(PGI2)水平。结果:与对照组比较,模型组大鼠mPAP、PASP和PADP明显升高(P<0.05或P<0.01),RVHI明显增加(P<0.01),肺小动脉周围炎症细胞浸润明显,肺组织中TNF-α和IL-6水平明显升高(P<0.01),肌性血管百分比和肺小动脉WT%明显升高(P<0.01),非肌性血管百分比和LA%明显降低(P<0.01),肺组织中ET-1水平和ET-1/PGI2比值明显升高(P<0.05或P<0.01)。与模型组比较,高剂量ECC-BYPⅢ组大鼠mPAP和PADP明显降低(P<0.05);与模型组比较,中和高剂量ECC-BYPⅢ组大鼠肺小动脉周围炎症细胞浸润明显改善,中和高剂量ECC-BYPⅢ组大鼠肺组织中TNF-α及IL-6水平、WT%及肌性血管百分比明显降低(PObjective:To investigate the improvement effect of effective-compound compatibility of Bufei Yishen prescrtion(ECC-BYPⅢ)on pulmonary hypertension(PH)of the rats induced by smoke and bacteria,and to preliminarily elucidate its mechanism.Methods:SPF SD rats were randomly divided into control group(n=9)and modeling group(n=140).The rats in control groujp were given conventional feeding,and the rats in modeling group were given cigarette-smoke and Klebsiellabacillus(Kp)to make the PH model.Then the rats in model group were divided into model group(n=10),low(n=9),medium(n=10),and high(n=10)doses(3.24,6.48 and 12.96 mg·kg^(-1)·d^(-1))of ECC-BYPⅢgroups,according to the equivalent pulmonary function of the rats among various groups.The rats in ECC-BYPⅢgroups were administered with different doses of ECC-BYPⅢ,respectively,and the rats in control and model groups were administered with same volume of solvent for 4 weeks.On the 29th day,the mean pulmonary artery pressure(mPAP),pulmonary artery systolic pressure(PASP),pulmonary artery diastolic pressure(PADP),and right ventricular hypertrophy index(RVHI)of the rats in various groups were measured.The lung tissues of the rats in various groups were taken out.Hematoxylin-eosin(HE)staining was used to detect the periarteriolar inflammation in lung tissue;victoria blue staining was used to detect the percentages of non-muscular,partial muscular,and muscular pulmonary arterioles in pulmonary arterioles of the rats,the percentages of wall thickness of pulmonary muscular arterioles in vessel diameter(WT%),and luminal area in pulmonary muscular arterioles(LA%).Enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of interleukin 6(IL-6),tumor necrosis factor(TNF-α),endothelin-1(ET-1),and protracyclin(PGI2)in lung tissue of the rats in various groups.Results:Compared with control group,the mPAP,PASP,PADP of the rats in model group were increased(P<0.05 or P<0.01),RVHI was increased(P<0.01),and there were obvious inflammatory cell infiltration around t

关 键 词：补肺益肾组分方Ⅲ 大鼠 SD 肺血管重构 炎症反应 肺小动脉肌化 

分 类 号：R544.1[医药卫生—心血管疾病] R563.9[医药卫生—内科学]