中医治疗肾性蛋白尿的方法及其机制
|
摘要
慢性肾脏病是指持续3个月以上肾脏结构与功能异常,以尿液、血液、肾脏结构异常为临床指标。蛋白尿是慢性肾脏病的重要临床表现,与肾小球损害亦密切相关,既是慢性肾脏病发生的病理表现,也是加快慢性肾脏病发展的一个重要病理因素。中医历经几千年发展,在治疗慢性肾脏病方面具有系统完善的理论基础与丰富的临床经验。借鉴中医治疗"精气外泄""腰痛""虚劳""尿血""水肿"的原则与方法,蛋白尿治疗总则为协调机体阴阳,恢复阴阳平衡,具体方法有祛瘀法、发汗法、利小便法、补脾固肾法、疏肝活络法及利湿解毒法等。古代及现代医家根据治则与治法,创立了行之有效的方剂。现代研究发现,中医方剂降低蛋白尿的机制主要有改善足细胞足突大面积融合、裂隙完全消失的病理表现,上调足细胞裂孔隔膜上nephrin和podocin蛋白的表达,免疫调节与减轻系统炎症,提高血清超氧化物歧化酶(SOD)水平及机体清除自由基的能力等。笔者现从经方、验方以及中成药这3个方面,论述治疗肾性蛋白尿的方法及其机制,为临床治疗慢性肾脏病、减少蛋白尿排泄及改善患者临床症状提供理论参考。
Chronic kidney disease( CKD) refers to abnormal renal structure and function for more than 3 months,and is characterized by abnormal urine,blood and kidney structure. As an important clinical manifestation of CKD,proteinuria is closely related to glomerular damage. It is not only a pathological manifestation of CKD,but also an important pathological factor to accelerate the development of CKD. After thousands of years of development,traditional Chinese medicine( TCM) has a systematic theoretical foundation and rich clinical experience in the treatment of CKD. By referring to the treatment principles and methods of "leakage of vital essence","low back pain","asthenia","blood urine"and "edema"in TCM,the general treatment principle of proteinuria is to coordinate the body Yin and Yang and restore the balance of Yin and Yang. Specific methods include removing blood stasis,sweating,urinating,invigorating the spleen and strengthening the kidney,smoothing liver and activating collaterals,and removing dampness and detoxification. Both ancient and modern physicians have established effective prescriptions according to the treatment principles and methods. Modern studies have showed that the mechanism of TCM to reduce proteinuria is mainly to improve the pathological manifestations of large area fusion of podocyte processes and complete disappearance of poddout,up-regulate the expression of nephrin and podocin,regulate immune,alleviate systemic inflammation, and improve the serum superoxide dismutase( SOD) level and the ability of the body to remove free radicals. The method and mechanism of treating renal proteinuria are discussed from three aspects: classical prescriptions,empirical prescriptions and the Chinese patent medicine. It provides a theoretical reference for the clinical treatment of chronic kidney disease,reducing the excretion of proteinuria and improving the clinical symptoms of the patients.
Chronic kidney disease( CKD) refers to abnormal renal structure and function for more than 3 months,and is characterized by abnormal urine,blood and kidney structure. As an important clinical manifestation of CKD,proteinuria is closely related to glomerular damage. It is not only a pathological manifestation of CKD,but also an important pathological factor to accelerate the development of CKD. After thousands of years of development,traditional Chinese medicine( TCM) has a systematic theoretical foundation and rich clinical experience in the treatment of CKD. By referring to the treatment principles and methods of "leakage of vital essence","low back pain","asthenia","blood urine"and "edema"in TCM,the general treatment principle of proteinuria is to coordinate the body Yin and Yang and restore the balance of Yin and Yang. Specific methods include removing blood stasis,sweating,urinating,invigorating the spleen and strengthening the kidney,smoothing liver and activating collaterals,and removing dampness and detoxification. Both ancient and modern physicians have established effective prescriptions according to the treatment principles and methods. Modern studies have showed that the mechanism of TCM to reduce proteinuria is mainly to improve the pathological manifestations of large area fusion of podocyte processes and complete disappearance of poddout,up-regulate the expression of nephrin and podocin,regulate immune,alleviate systemic inflammation, and improve the serum superoxide dismutase( SOD) level and the ability of the body to remove free radicals. The method and mechanism of treating renal proteinuria are discussed from three aspects: classical prescriptions,empirical prescriptions and the Chinese patent medicine. It provides a theoretical reference for the clinical treatment of chronic kidney disease,reducing the excretion of proteinuria and improving the clinical symptoms of the patients.
引文
[1]陈志远,何学红.“开鬼门,洁净府”与慢性肾功能衰竭[J].实用中医内科杂志,2016,30(5):47-48.
[2]苏克雷,郭立中.猪苓汤治疗慢性肾脏病临床及实验研究进展[J].中医学报,2010,25(3):589-592.
[3]何岚,王宁生.五苓散减轻阿霉素肾病大鼠蛋白尿的实验研究[J].中成药,2006,28(10):1532-1534.
[4]张保国,刘庆芳.猪苓汤的现代药理研究与临床应用[J].中成药,2014,36(8):1726-1729.
[5]徐文峰,何泽云,唐群,等.猪苓汤对阿霉素肾病大鼠肾脏AQP2表达的影响[J].中国中西医结合肾病杂志,2013,14(9):759-763.
[6]李亚丽,李志杰,张燕,等.真武汤对阿霉素所致大鼠肾损伤的治疗作用[J].中国病理生理杂志,2013,29(11):1994-2000.
[7]黄刚,叶一萍.真武汤合当归芍药散治疗原发性肾病综合征的疗效观察[J].中华中医药学刊,2017,35(2):488-491.
[8]陈洪宇,揭乐琴,王永钧,等.防己黄芪汤加减干预对阿霉素肾病大鼠肾组织MCP-1表达的影响[J].中国中西医结合肾病杂志,2011,12(11):958-962,1035.
[9] WANG X L,LIU X,XU X Y,et al. Screening and identification of multiple complex constituents of Fangji Huangqi Tang in vitro and in vivo by UHPLC-Q-TOF-MS method[J]. J Chromatogr B,2015,985:14-28.
[10]刘书芬,梁倩倩,陈岩,等. HPLC法同时测定防己黄芪汤中5种成分[J].中成药,2014,36(11):2312-2315.
[11]张珂.防己黄芪汤中生物碱及皂苷的质量控制及抗氧化、抑菌活性研究[D].西安:陕西师范大学,2012.
[12]闫艳,杜晨晖,张淑蓉,等.防己黄芪汤合煎与分煎药理作用比较研究[J].山西中医学院学报,2011,12(1):23-24,78.
[13]汪小莉,刘晓,夏春燕,等.防己黄芪汤药理作用及各单味药化学成分研究进展[J].中草药,2016,47(19):3527-3534.
[14]赖宗甫.《金匮要略》防己黄芪汤治疗肾病综合征疗效观察[D].广州:广州中医药大学,2012.
[15]魏科.防己黄芪胶囊对痰湿壅盛型高血压病尿酸代谢的影响[D].郑州:河南中医学院,2015.
[16]陈焱.防己黄芪汤对脑缺血再灌注模型大鼠脑损伤的保护作用[J].中国实验方剂学杂志,2015,21(12):134-138.
[17]李彬,张家衡,柯有力,等.防己黄芪汤对单肺通气患者的保护作用[J].中国实验方剂学杂志,2012,18(5):223-226.
[18]俞东容,杨汝春,林宜,等.防己黄芪汤对阿霉素肾病大鼠蛋白尿及足细胞病变的影响[J].中国中西医结合肾病杂志,2009,10(4):295-298,377.
[19]刘玲.防己茯苓汤治疗肾病综合征体会[J].中国民族民间医药,2010,19(22):188-189.
[20]程偲婧.汗法调节肠道微生态治疗慢性肾脏病的研究[D].成都:西南医科大学,2017.
[21]李雯雯,沈沛成.麻黄连翘赤小豆汤治疗慢性肾小球肾炎研究概况[J].辽宁中医药大学学报,2016,18(3):85-87.
[22]丁丽丽,施松善,崔健,等.麻黄化学成分与药理作用研究进展[J].中国中药杂志,2006,31(20):1661-1664.
[23]赵杰,余林中,方芳,等.麻黄/甘草药对的抗炎作用及机制研究[J].中国实验方剂学杂志,2012,18(15):163-166.
[24]李双,王东强,李志军.连翘药理作用小议[J].西部中医药,2012,25(1):52-54.
[25]游元元,万德光,杨文宇,等.四种桑类药材对小鼠免疫功能的影响[J].中药药理与临床,2008,24(3):83-84.
[26]王军,徐阳,袁向科,等.实验性糖尿病鼠大血管病变TGF-β1和CTGF的表达及中药的干预作用[J].天津中医药,2012,29(3):266-269.
[27]王刚,徐阳,王军,等.加味桃核承气汤对糖尿病大鼠皮肤微血管CD34表达的影响[J].中国中西医结合外科杂志,2013,19(3):283-286.
[28]赵治友,邬亚军,张俊杰,等.加味桃核承气汤对肝纤维化大鼠TGF-β1蛋白表达的影响[J].浙江中医药大学学报,2010,34(2):166-168.
[29]陈光晖,陈子珺,陈德兴.桃核承气汤及其拆方组对蓄血症大鼠模型“瘀热”相关指标的影响[J].中国实验方剂学杂志,2012,18(21):282-286.
[30]孙霞,王兴华.经方在糖尿病及其并发症中的应用[J].长春中医药大学学报,2013,29(2):353-355.
[31]刘彦琴.加味桃仁承气汤对内毒素性大鼠DIC及肺损伤的研究[D].沈阳:辽宁中医药大学,2007.
[32]郑灵琳.桃核承气汤对促肾纤维化启动及下游因子的调控作用[D].哈尔滨:黑龙江中医药大学,2010.
[33]赵艳明,郑灵琳,符强.桃核承气汤对肾小球硬化大鼠肾组织病理的影响[J].中医药学报,2010,38(2):37-39.
[34]赵艳明,纪宝华,符强.桃核承气汤对肾小球硬化大鼠肾功能的改善作用[J].中国中医急症,2012,21(3):390-391.
[35]朱永强.加减桃核承气汤(消渴平胶囊)治疗实验性糖尿病合并高血压大鼠的实验研究及对正常小鼠空腹血糖水平的影响[D].福州:福建中医学院,2007.
[36]王付.经方学用基本功[M].北京:人民军医出版社,2012:6.
[37]王付,王林玉.桂枝茯苓丸方证思考与探索[J].中华中医药杂志,2016,31(7):2618-2620.
[38]李青,韩宇博.金匮肾气丸联合美卡素治疗Ⅲ期糖尿病肾病的临床研究[J].光明中医,2014,29(3):576-578.
[39]展照双,齐丽娟,吕翠霞,等.肾气丸与右归丸对肾虚大鼠肾脏细胞凋亡及肾组织内Bcl-2、fas表达的影响[J].山东中医杂志,2011,30(6):412-414.
[40]赵乐,李艳彦.从免疫角度探讨黄芪桂枝五物汤对小鼠衰老皮肤瘙痒模型的影响[J].中国实验方剂学杂志,2016,22(4):127-131.
[41]韩兆莹,田明,刘珍,等.黄芪桂枝五物汤的药理研究现状[J].黑龙江医药,2013,26(5):777-779.
[42]王国明,张永健.当归四逆汤的应用和实验研究进展[J].现代中西医结合杂志,2012,21(13):1479-1482.
[43]王付.当归四逆汤方证探索与实践[J].中医药通报,2017,16(4):9-12.
[44]戴芹,张佩青,王小琴,等.益肾清热化湿方治疗脾肾两虚兼湿热证慢性肾小球疾病蛋白尿的临床研究[J].中国中西医结合杂志,2015,35(9):1039-1043.
[45]屈欢欢,陈小娟,何岩,等.健脾祛湿和络方治疗原发性肾小球疾病蛋白尿50例临床观察[J].中医杂志,2013,54(21):1834-1836.
[46]陈刚,吴同茹,朱祎,等.益气养阴方治疗原发性慢性肾小球疾病蛋白尿的临床观察[J].中国中西医结合肾病杂志,2013,14(10):868-871.
[47]晋中恒,蒋松,王建华,等.健脾益肾清化法治疗慢性肾小球肾炎气虚湿热瘀阻证蛋白尿、血尿的临床疗效观察[J].河北中医,2017,39(6):819-824,843.
[48]蒋军艳,李欣玲,樊泽锋,等.百令胶囊联合西药治疗慢性肾小球肾炎临床疗效的Meta分析[J].湖南中医药大学学报,2017,37(12):1363-1368.
[49]沈烨渠,廖顺花,孙悦,等.黄葵胶囊治疗慢性肾炎CKDⅢ期37例[J].中国实验方剂学杂志,2014,20(10):205-208.
[50] Tsampalieros A, Gupta P, Denburg M R, et al.Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome[J]. J Bone Miner Res, 2013,28(3):480-488.
[51]曾宪涛,章友康,艾金伟,等.肾炎康复片联合激素治疗肾病综合征有效性Meta分析[J].中国实用内科杂志,2016,36(10):891-897.
[52]郑芳蓉.肾复康胶囊联合阿魏酸钠治疗慢性肾小球肾炎的临床研究[J].现代药物与临床,2016,31(4):496-499.
[2]苏克雷,郭立中.猪苓汤治疗慢性肾脏病临床及实验研究进展[J].中医学报,2010,25(3):589-592.
[3]何岚,王宁生.五苓散减轻阿霉素肾病大鼠蛋白尿的实验研究[J].中成药,2006,28(10):1532-1534.
[4]张保国,刘庆芳.猪苓汤的现代药理研究与临床应用[J].中成药,2014,36(8):1726-1729.
[5]徐文峰,何泽云,唐群,等.猪苓汤对阿霉素肾病大鼠肾脏AQP2表达的影响[J].中国中西医结合肾病杂志,2013,14(9):759-763.
[6]李亚丽,李志杰,张燕,等.真武汤对阿霉素所致大鼠肾损伤的治疗作用[J].中国病理生理杂志,2013,29(11):1994-2000.
[7]黄刚,叶一萍.真武汤合当归芍药散治疗原发性肾病综合征的疗效观察[J].中华中医药学刊,2017,35(2):488-491.
[8]陈洪宇,揭乐琴,王永钧,等.防己黄芪汤加减干预对阿霉素肾病大鼠肾组织MCP-1表达的影响[J].中国中西医结合肾病杂志,2011,12(11):958-962,1035.
[9] WANG X L,LIU X,XU X Y,et al. Screening and identification of multiple complex constituents of Fangji Huangqi Tang in vitro and in vivo by UHPLC-Q-TOF-MS method[J]. J Chromatogr B,2015,985:14-28.
[10]刘书芬,梁倩倩,陈岩,等. HPLC法同时测定防己黄芪汤中5种成分[J].中成药,2014,36(11):2312-2315.
[11]张珂.防己黄芪汤中生物碱及皂苷的质量控制及抗氧化、抑菌活性研究[D].西安:陕西师范大学,2012.
[12]闫艳,杜晨晖,张淑蓉,等.防己黄芪汤合煎与分煎药理作用比较研究[J].山西中医学院学报,2011,12(1):23-24,78.
[13]汪小莉,刘晓,夏春燕,等.防己黄芪汤药理作用及各单味药化学成分研究进展[J].中草药,2016,47(19):3527-3534.
[14]赖宗甫.《金匮要略》防己黄芪汤治疗肾病综合征疗效观察[D].广州:广州中医药大学,2012.
[15]魏科.防己黄芪胶囊对痰湿壅盛型高血压病尿酸代谢的影响[D].郑州:河南中医学院,2015.
[16]陈焱.防己黄芪汤对脑缺血再灌注模型大鼠脑损伤的保护作用[J].中国实验方剂学杂志,2015,21(12):134-138.
[17]李彬,张家衡,柯有力,等.防己黄芪汤对单肺通气患者的保护作用[J].中国实验方剂学杂志,2012,18(5):223-226.
[18]俞东容,杨汝春,林宜,等.防己黄芪汤对阿霉素肾病大鼠蛋白尿及足细胞病变的影响[J].中国中西医结合肾病杂志,2009,10(4):295-298,377.
[19]刘玲.防己茯苓汤治疗肾病综合征体会[J].中国民族民间医药,2010,19(22):188-189.
[20]程偲婧.汗法调节肠道微生态治疗慢性肾脏病的研究[D].成都:西南医科大学,2017.
[21]李雯雯,沈沛成.麻黄连翘赤小豆汤治疗慢性肾小球肾炎研究概况[J].辽宁中医药大学学报,2016,18(3):85-87.
[22]丁丽丽,施松善,崔健,等.麻黄化学成分与药理作用研究进展[J].中国中药杂志,2006,31(20):1661-1664.
[23]赵杰,余林中,方芳,等.麻黄/甘草药对的抗炎作用及机制研究[J].中国实验方剂学杂志,2012,18(15):163-166.
[24]李双,王东强,李志军.连翘药理作用小议[J].西部中医药,2012,25(1):52-54.
[25]游元元,万德光,杨文宇,等.四种桑类药材对小鼠免疫功能的影响[J].中药药理与临床,2008,24(3):83-84.
[26]王军,徐阳,袁向科,等.实验性糖尿病鼠大血管病变TGF-β1和CTGF的表达及中药的干预作用[J].天津中医药,2012,29(3):266-269.
[27]王刚,徐阳,王军,等.加味桃核承气汤对糖尿病大鼠皮肤微血管CD34表达的影响[J].中国中西医结合外科杂志,2013,19(3):283-286.
[28]赵治友,邬亚军,张俊杰,等.加味桃核承气汤对肝纤维化大鼠TGF-β1蛋白表达的影响[J].浙江中医药大学学报,2010,34(2):166-168.
[29]陈光晖,陈子珺,陈德兴.桃核承气汤及其拆方组对蓄血症大鼠模型“瘀热”相关指标的影响[J].中国实验方剂学杂志,2012,18(21):282-286.
[30]孙霞,王兴华.经方在糖尿病及其并发症中的应用[J].长春中医药大学学报,2013,29(2):353-355.
[31]刘彦琴.加味桃仁承气汤对内毒素性大鼠DIC及肺损伤的研究[D].沈阳:辽宁中医药大学,2007.
[32]郑灵琳.桃核承气汤对促肾纤维化启动及下游因子的调控作用[D].哈尔滨:黑龙江中医药大学,2010.
[33]赵艳明,郑灵琳,符强.桃核承气汤对肾小球硬化大鼠肾组织病理的影响[J].中医药学报,2010,38(2):37-39.
[34]赵艳明,纪宝华,符强.桃核承气汤对肾小球硬化大鼠肾功能的改善作用[J].中国中医急症,2012,21(3):390-391.
[35]朱永强.加减桃核承气汤(消渴平胶囊)治疗实验性糖尿病合并高血压大鼠的实验研究及对正常小鼠空腹血糖水平的影响[D].福州:福建中医学院,2007.
[36]王付.经方学用基本功[M].北京:人民军医出版社,2012:6.
[37]王付,王林玉.桂枝茯苓丸方证思考与探索[J].中华中医药杂志,2016,31(7):2618-2620.
[38]李青,韩宇博.金匮肾气丸联合美卡素治疗Ⅲ期糖尿病肾病的临床研究[J].光明中医,2014,29(3):576-578.
[39]展照双,齐丽娟,吕翠霞,等.肾气丸与右归丸对肾虚大鼠肾脏细胞凋亡及肾组织内Bcl-2、fas表达的影响[J].山东中医杂志,2011,30(6):412-414.
[40]赵乐,李艳彦.从免疫角度探讨黄芪桂枝五物汤对小鼠衰老皮肤瘙痒模型的影响[J].中国实验方剂学杂志,2016,22(4):127-131.
[41]韩兆莹,田明,刘珍,等.黄芪桂枝五物汤的药理研究现状[J].黑龙江医药,2013,26(5):777-779.
[42]王国明,张永健.当归四逆汤的应用和实验研究进展[J].现代中西医结合杂志,2012,21(13):1479-1482.
[43]王付.当归四逆汤方证探索与实践[J].中医药通报,2017,16(4):9-12.
[44]戴芹,张佩青,王小琴,等.益肾清热化湿方治疗脾肾两虚兼湿热证慢性肾小球疾病蛋白尿的临床研究[J].中国中西医结合杂志,2015,35(9):1039-1043.
[45]屈欢欢,陈小娟,何岩,等.健脾祛湿和络方治疗原发性肾小球疾病蛋白尿50例临床观察[J].中医杂志,2013,54(21):1834-1836.
[46]陈刚,吴同茹,朱祎,等.益气养阴方治疗原发性慢性肾小球疾病蛋白尿的临床观察[J].中国中西医结合肾病杂志,2013,14(10):868-871.
[47]晋中恒,蒋松,王建华,等.健脾益肾清化法治疗慢性肾小球肾炎气虚湿热瘀阻证蛋白尿、血尿的临床疗效观察[J].河北中医,2017,39(6):819-824,843.
[48]蒋军艳,李欣玲,樊泽锋,等.百令胶囊联合西药治疗慢性肾小球肾炎临床疗效的Meta分析[J].湖南中医药大学学报,2017,37(12):1363-1368.
[49]沈烨渠,廖顺花,孙悦,等.黄葵胶囊治疗慢性肾炎CKDⅢ期37例[J].中国实验方剂学杂志,2014,20(10):205-208.
[50] Tsampalieros A, Gupta P, Denburg M R, et al.Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome[J]. J Bone Miner Res, 2013,28(3):480-488.
[51]曾宪涛,章友康,艾金伟,等.肾炎康复片联合激素治疗肾病综合征有效性Meta分析[J].中国实用内科杂志,2016,36(10):891-897.
[52]郑芳蓉.肾复康胶囊联合阿魏酸钠治疗慢性肾小球肾炎的临床研究[J].现代药物与临床,2016,31(4):496-499.