调补肺肾三法对慢性阻塞性肺疾病大鼠肾损伤的影响  

Effect of three Tiao-Bu Fei-Shen therapies on renal injury in rats with chronic obstructive pulmonary disease

作　　者：范正媛 韩迪 李亚[1,3] 韩冰洋 李素云[2,3] FAN Zhengyuan;HAN Di;LI Ya;HAN Bingyang;LI Suyun(Chinese Medicine Pharmacology(Respiratory)Laboratory,the First Affiliated Hospital of Henan University of Chinese Medicine,Henan Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Respiratory Diseases,Zhengzhou 450000,China;Respiratory Department of the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of China,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学第一附属医院中药药理(呼吸)实验室河南省呼吸病防治中医药重点实验室,河南郑州450000 [2]河南中医药大学第一附属医院呼吸科,河南郑州450000 [3]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,河南郑州450046

出　　处：《中国病理生理杂志》2024年第9期1688-1699,共12页Chinese Journal of Pathophysiology

基　　金：国家重点研发计划项目(No.2018YFC1704800,No.2018YFC1704801);国家自然科学基金资助项目(No.82074413,No.82374416);河南省科技研发计划联合基金项目(No.222301420081)。

摘　　要：目的:探讨调补肺肾三法对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠肾损伤的影响及机制。方法:将SPF级SD大鼠随机分为对照(control)组、COPD组、吡咯烷二硫代甲酸铵(pyrrolidinedithiocarbamate ammonium,PDTC)组、补肺健脾方(Bufei-Jianpi formula,BJF)组、补肺益肾方(Bufei-Yishen formula,BYF)组、益气滋肾方(Yiqi-Zishen formula,YZF)组、BJF联合PDTC(BJF+PDTC)组、BYF联合PDTC组(BYF+PDTC)和YZF联合PDTC(YZF+PDTC)组。采用香烟烟雾暴露联合细菌感染的方法建立COPD稳定期大鼠模型,筛选COPD肾损伤大鼠进行后续治疗。第16周末取材观察大鼠肺、肾功能;HE染色观察肺、肾病理形态学;检测24 h尿量和尿生化指标;免疫组化检测水通道蛋白(aquaporins,AQPs)水平;取支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)进行细胞分类计数;测定血清炎症因子水平及肾组织IKK和NF-κB的mRNA和蛋白表达变化。结果:与control组比较,COPD大鼠肺功能指标用力肺活量(forced expiratory vital capacity,FVC)、第0.1秒用力呼气容积(forced expiratory volume in 0.1 second,FEV_(0.1))及FEV_(0.1)/FVC显著降低(P<0.05),肺组织病理表现为肺泡壁断裂、融合,气道炎症细胞浸润;肾功能指标血清肌酐(creatinine,Cr)、血尿素氮(blood urea nitrogen,BUN)及血清胱抑素C(cystatin C,Cys-C)水平显著升高(P<0.01);肾组织病理表现为肾小管上皮细胞肿胀、排列紊乱;24 h尿量降低(P<0.01),尿生化指标24 h尿总蛋白、尿肾损伤分子1、尿Cys-C和尿N-乙酰-β-D-氨基葡萄糖苷酶水平显著升高(P<0.01),肾小管AQP1~4蛋白水平显著升高(P<0.01);BALF中性粒细胞和淋巴细胞百分比增高(P<0.01),单核细胞百分比降低(P<0.01);血清炎症因子TNF-α、IL-6、IL-13、IL-1β和TGF-β1水平显著升高(P<0.01),肾组织IKK和NF-κB的mRNA和蛋白表达水平显著升高(P<0.05)。与COPD组比较,各治疗组干预后大鼠上述症状及指标均有不同程度的改善,其中AIM:To investigate the effects of the three Tiao-Bu Fei-Shen therapies on renal injury in rats with chronic obstructive pulmonary disease(COPD),and to explore the mechanisms.METHODS:SPF-grade SD rats were randomly divided into control,COPD,pyrrolidinedithiocarbamate ammonium(PDTC),Bufei-Jianpi formula(BJF),Bufei-Yishen formula(BYF),Yiqi-Zishen formula(YZF),BJF combined with PDTC(BJF+PDTC),BYF combined PDTC(BYF+PDTC),and YZF combined PDTC(YZF+PDTC)groups.Cigarette smoke exposure combined with bacterial infection were used to develop a stable-phase rat model of COPD,and kidney-injured rats were screened for subsequent treatment.Pulmonary and renal functions,pathological changes in lung and kidney tissues,24 h urine volume,urine biochemical indexes,aquaporin(AQP)levels,ratio of inflammatory cells in the bronchoalveolar lavage fluid(BALF),serum inflammatory factor levels,and mRNA and protein expressions of IκB kinase(IKK)and nuclear factor-κB(NF-κB)were observed at the end of the 16th week.RESULTS:Compared with control group,the rats in COPD group showed reduced lung function indexes of forced expiratory vital capacity(FVC),forced expiratory volume in 0.1 second(FEV_(0.1))and FEV_(0.1)/FVC(P<0.05).The lung histopathology exhibited alveolar wall fracture and fusion and airway inflammatory cell infiltration.The renal function indexes serum creatinine,blood urea nitrogen and serum cystatin C(Cys-C)were significantly increased(P<0.01).The renal histopathology showed swollen and disorderly arranged tubular epithelial cells.The 24 h urine volume decreased(P<0.01).The urinary biochemical indexes 24 h urinary total protein,urinary kidney injury molecule-1(KIM-1),urinary Cys-C,and urinary N-acetyl-β-D-glucosaminidase significantly increased(P<0.01).The protein levels of AQP1~4 were significantly increased(P<0.01).The ratio of neutrophils and lymphocytes in the BALF were increased(P<0.01).The ratio of monocytes was decreased(P<0.01).The serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-13,IL-1β,and tra

关 键 词：调补肺肾三法 慢性阻塞性肺疾病 肾损伤 水通道蛋白 NF-ΚB信号通路 

分 类 号：R563[医药卫生—呼吸系统] R363.2[医药卫生—内科学] R285[医药卫生—临床医学]