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肾炎止血丸对IgA肾病大鼠肾小管间质损伤影响的实验研究
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摘要
目的:通过肾炎止血丸对IgA肾病(IgAN)大鼠肾小管间质损伤影响的实验研究,进一步探讨本病发生发展机制,为肾炎止血丸改善肾小管间质损伤的作用机理提供较为深入的理论及实验依据。
     方法:通过给大鼠口服牛血清白蛋白酸化水和尾静脉注射牛血清白蛋白及葡萄球菌肠毒素B复合方法建立IgAN模型,观测肾炎止血丸对IgAN大鼠尿红细胞计数、24小时尿蛋白定量、肾功能、肝功能、肾小管功能的敏感指标尿视黄醇结合蛋白(RBP)及N-乙酰-β-D氨基葡萄糖苷酶(NAG)的影响,同时利用光镜、免疫荧光、免疫组化及Motic image 3.2图像分析软件分别观察肾组织(肾小管-间质)的病理改变、肾小球系膜区IgA的沉积情况及核转录因子-κB(NF-κB)和巨噬细胞移动抑制因子(MIF)在肾小管-间质的表达情况及定量分析。
     结果:1.肾炎止血丸能减少尿红细胞及尿蛋白,降低血肌酐及尿素氮保护肾功能,降低尿RBP、NAG酶改善肾小管功能,总体疗效优于雷公藤对照组(P<0.05),且无雷公藤多甙片对肝功能损害的副作用;2.减少IgA在肾小球系膜区的沉积,减轻肾小球损伤;3.减轻肾小球及肾小管间质的病理损害;4.可能通过降低NF-κB的活性进而减少肾组织MIF等炎症介质水平,调节炎症细胞因子,减轻炎症反应对肾小管间质的损伤。
     结论:肾炎止血丸对IgAN肾小管间质损伤有显著的防治作用,总体疗效优于雷公藤多甙片对照组,为临床进一步应用提供了理论依据。
Objective: Through experimental study on the effect of tubulointerstitium injur of IgA nephropathy(IgAN)in rat with SHEN-YAN-ZHI-XUE pill, further discusses this sickness to have the development mechanism,for SHEN-YAN-ZHI-XUE pill to improve tubulointerstitial injury mechanism to provide a more thorough theoretical and experimental basis.
     Methods:The oral administration to rats with bovine serum albumin acidification of water and tail vein injection of bovine serum albumin and staphylococcal enterotoxin B complex method IgAN model, observation of IgAN SHEN-YAN-ZHI-XUE pill urine red blood cell count in rats, a 24-hour urinary protein, the kidney function, the liver function, a sensitive indicator of renal tubular function in urinary retinol-binding protein (RBP) and N-acetyl-β-D-glucosaminidase (NAG), simultaneously using the light microscope, immunofluorescence, immunohistochemistry and Motic the image 3.2 image analysis software observes the kidney organization (tubular-mesenchymal) the pathology change, the renal glomerulus are the membrane area IgA deposition situation and the nucleus transcription factor -κB (NF-κB) and macrophage migration inhibiting factor (MIF) in tubulus renalis - mesenchymal expression situation and quantitative analysis.
     Results:1.SHEN-YAN-ZHI-XUE pill can reduce the red blood cells in urine and urinary protein, lower serum creatinine and blood urea nitrogen, protect the renal function, lower urinary RBP, NAG enzyme the protection of renal tubular function,the overall effect is better than the control group tripterygium(P<0.05), and does not have the Tripterygium wilfordii multi-glucoside piece to the liver function harm side effect; 2. To reduce IgA in the glomerular mesangial areas of deposition, to reduce glomerular injury; 3. To reduce the glomerular and tubulointerstitial injury pathology; 4. May reduce NF-κB activity then ruduce the renal tissue level of MIF and other inflammatory mediators, regulation of inflammatory cytokines and reduce inflamema- tory reaction of tubulointerstitial injury.
     Conclusion:SHEN-YAN-ZHI-XUE pill has the remarkable prevention function to the tubulointerstitium injur of IgAN, the overall curative effect surpasses the Tripterygium wilfordii multi-glucoside piece control group, for clinical further applied has provided the theory basis.
引文
1.易岚,孙伟,曾安平,等.从脾论治rgA肾病[J].中国中医药信息杂志,2003,10(2):5-6.
    2.陈香美,陈以平,李平,等.1016例IgA肾病患者中医证候的多中心流行病调查及相关因素分析[J].中国中西医结合杂志,2006,26(3):197-201.
    3.高国青.IgA肾病的中医研究现状[J].山西中医杂志,2006,22(2):58-60.
    4.王今朝,黄彦彬.再析张琪教授治疗IgA肾病血尿的经验[J].黑龙江中医药,2005,2:4-5.
    5.洪钦国.罗月中.重视IgA肾病的中医研究[J].新中医,2002,34(9):3-4.
    6.程军,张雯,陶筱娟.陶筱娟治疗IgA肾病的经验[J].中国中西医结合肾病杂志,2003,4(5):291—292.
    7.孙瑞涛.王铁良教授治疗IgA肾病的临证经验浅析[J].中医药学刊,2005,23(2):230.
    8.潘莉,成秀梅,常风云.益气活血通络法治疗以血尿为主IgA肾病患者32例[J].中医杂志,2008,49(8):718.
    9.钟清.陈贤教授治疗IgA肾病的临证经验[J].中国中西医结合肾病杂志,2004,5(4):189-190.
    10.聂莉芳,孙伟,张佩青,等. IgA肾病的诊断、辨证分型和疗效评定(试行方案) [J].上海中医药杂志,2007,41(5):9-10.
    11.周柱亮. IgA肾病的分型与治疗[J].中国中西医结合肾病杂志,2007,8(2):63-65.
    12.孙建实.IgA肾病肾活检病理与中医辨证关系的研究[J].中国中西医结合肾病杂志,2004 , 5 (9) :510-514.
    13.陈香美,陈以平,谌贻璞,等. 286例IgA肾病中医辨证与肾脏病理关系的多中心前瞻性研究[J].中国中西医结合杂志,2004,24(2):101-105.
    14.余秉治,边红萍. IgA肾病中医证型与Lee氏分级和Ka氏评分关系探讨[J].中国中西医结合肾病杂志,2006,7(11):657-658.
    15.朱斌,楼季华,俞东蓉. IgA肾病免疫病理和中医辨证的关系[J].浙江中医学院学报,2001,25(2):35.
    16.王安新.聂莉芳教授治疗IgA肾病的经验[J].四川中医,2001,19(4):4.
    17.杜玉屏,陈以平.中药治疗IgA肾病经验[J].辽宁中医杂志,2001,28(4):204.
    18.李良,中医辨证论治IgA肾病60例[J].上海中医药杂志,2002;8:24.
    19.金仲达,曹向东,张文军.中药为主治疗IgA肾病43例[J].中国中西医结合肾脏病杂志, 2002, 5 (3) : 296.
    20.金亚明,朱戎,陈以平.中药治疗血尿为主IgA肾病32例[J].江苏中医, 2001, 22(3) :14.
    21.张铎,云锐,郭晓燕,等.中西医结合治疗IgA肾病临床观察[J].内蒙古中医药,2000,2:18-20.
    22.李夏玉.火把花根片合益气养阴方剂治疗IgA肾病45例[J].浙江中医杂志,2000,35(9):472.
    23.王宇晖,王永钧. 110例IgA肾病中西医结合治疗的临床研究[J].浙江中医杂志, 2000, 35 (6) : 256.
    24.王青.中西医结合治疗IgAN[J].中华临床医学研究杂志,2005,11(22):3260-3261.
    25.于梅,张佩青,迟继铭等.益肾汤防治IgA肾病肾小管-间质损伤的临床研究[J].中医药信息.2007,24(6):31-33.
    26.李玉清,杨春霞.自拟益肾固本汤加减治疗血尿为主IgA肾病5O例的临床观察[J].北京中医.2006, 25 (8) : 451– 453.
    27.陈香美,陈建,陈以平,等.肾华片治疗IgA肾病(气阴两虚型)多中心随机对照临床观察[J].中国中西医结合杂志,2007,27(3):101—105.
    28.李静.双倍剂量雷公藤多苷在大量蛋白尿型IgA肾病中的疗效观察[J].中国医药导报,2007,4(16):59.
    29.周红星.百令胶囊治疗IgA肾病血尿的疗效观察[J].中医研究,2002,15(4):26-27.
    30.庄永泽. IgA肾病治疗的研究进展[J].国外医学.泌尿系统分册,1995,(5):204.
    31.朱起之.柴胡治疗IgA肾病的初步研究[J].广东医学,2002,23(9):992-993.
    32.王智,吴竞,郑京等.复方丹参注射液联合东莨菪碱治疗以血尿为主要表现IgA肾病的临床观察[J].中国中西医结合肾病杂志,2004,5(8):479-480.
    33.王强,徐珩,张乐新.黄芪注射液对IgA肾病患者血液流变学的影响[J].安徽中医临床杂志,2002,14(3):183-184.
    34.王晓亮,王晓丹,白云凯. IgA肾病研究进展[J].医学综述,2007,11(21):1628-1630.
    35.陈洪宇,王永钧. IgA肾病发病机理的研究进展[J].中国中西医结合肾病杂志,2004,5(7):427.
    36. Julian BA,Novak J.IgA nephropathy:an update[J].Curt Opin NephrolHypcrtens. 2004,13(2):171-79.
    37. Yuansheng Xie, Xiangmei Chen, Shinichi Nishi, etal. Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy[J].Kidney International,2004,65:1135.
    38.鲁盈. IgA肾病的病因与发病机制[J].临床肾脏病杂志,2004,4(1):33-34.
    39. Renfrow MB,CooperHJ,TomanaM, a1.Determination of aberrant O-glyeosylationin the IgA1 hinge region by electron capture dissociationfourier transform-ion cyclotron resonance spectrometry[J].J Biol Chem.2005,280(19):19136-45.
    40. Leung Jc,Tang SC,Lam MF,et al.Charge-dependent binding of polymeric IgA to human mesangial cells in IgA nephropathy[J].Kidnay Int,2001,59(1):277-285.
    41.涂小刚,程晓霞.IgA肾病发病机理的研究新进展[J].吉林医学,2007,28(3):426-427.
    42. Leung JC,Tsang AW ,Chart DT,et a1.Absence of CD89,polymeric immunoglobulin receptor ,and asialoglycoprotein receptor on human mesangial cells[J].J Am Soc Nephro1.2000,11(2):241—9.
    43. Haddad E,Moura IC,Arcos—Fajardo M,et a1.Enhanced expression of the CD71 mesangial IgA1 receptor in Berger disease and Henoeh-Schonlein nephritis:association between CD71 expression and IgA deposits[J]. J Am Soc Nephrol,2003,14(2):327.
    44. HaddadE,MouraIC,Amos-FajardoM,eta1.Enhanced expression of the CD71 mesangial IgA1 receptor in Berger disease and Henoch-Schonlein nephritis:association between CD71 expression and IgA deposits[J].J Am Soc Nephro1.2003,14(2):327-37.
    45. Moura IC,Arcos-Fajardo M,Sadaka C,et al.Glycosylation and size of IgA1 Are Essential for interaction with mesangial transferring receptor in IgA neph- ropathy[J].J Am Soc Nephrol,2004,15:622-634.
    46. Monteiro RC.Van DeWinkd JG.IgA Fc receptors[J].Annu Rcv Immuno1.2003,21:177—204.
    47. Lu JC,Zhang H,Chen YQ,et a1 .Uteroglobin IgA polymorphismis associated with the progression of Igh nephropathy in Chinese patients[J].Zhonghua Nei Ke Za Zhi.2004,43(1):37—40.
    48. Sato F ,NaritaI,Goto S ,eta1.Transforming growthfactor-betalgene polymorph- ism lnodics the histologica: and clinical manifestationsin Japanese patients with IgA nephropathy[J].Tissue Antigens,2004,54 (1):35-42.
    49.邢昌赢.控制炎证反应在肾间质损害中的作用[J].中华医学会肾脏病学分会2004年会暨第二届全国中青年肾脏病学术会议专题讲座汇编, 2004,9:149-150.
    50.余学清.炎症在慢性肾脏疾病进行性发展中的作用及防治的提示[J].中华医学会肾脏病学分会2004年会暨第二届全国中青年肾脏病学术会议专题讲座汇编. 2004,9:34-35.
    51. FuJiinaqa S,Ohtomo Y.Plasma Exchange combined with im- munosuppr-essive treatment in a child with rapidly prog-ressive IgA nephropathy[J].Pediatr Nephrol,2007,22(6):899—902.
    52. Hui YL,Niansheng Y,David JNP,etal.Expression of macrophage migration inhibitory factor in human glom erul on ephritis[J].Kidney Int.2000, 57: (499-509).
    53. Nicole MI , David JNP,Prudence AH , et al.Local macrophage proliferation correlates with increased renal M-CSF expression in human glomerulonephritis[J].Nephrol Dial Transplant, 16:1638-1647 David CHH: Tubulointerstitial renal disease.Curr Opin Nephrol Hypertens,2001,10: 303-313
    54.陈威,杨守京,刘彦仿,等.实验性慢性肾缺血模型肾小管-间质细胞α-平滑肌肌动蛋白的表达和意义[J].肾脏病与透析肾移植杂志,2004, 13(1):30-34.
    55. Arrizabalaga P, Sole M, Quito IL, et al.Intercellular adhesion molecule- 1mediated interactions and leucocyte infiltration in IgA nephropathy[J]. Nephrol Dial transplant, 1997,12:2258-2262.
    56.李江涛,李素. IgA肾病发病机制的研究进展[J].同济大学学报,2002,23(5):442-444.
    57.刘军,胡宏慧,姚建,等. IgA肾病患者组织中Tenascin表达的意义[J].肾脏病与透析肾移植杂志,2001,10(2):138-139.
    58.方一卿.血管紧张转换抑制剂和血管紧张素拮抗剂在IgA肾病中的应用[J].临床肾脏病杂志,2004,4(1):37-38.
    59.邱强,孙雪峰,陈香美等.尿激酶对IgA肾病毛细血管密度的影响[J].军事医学科学院院刊,2008,32(2):148-150.
    60.李霞,郝洁.尿激酶联合雷公藤多甙片治疗IgA肾病的临床观察[J].实用全科医学,2006,4(4):410-411.
    61. Hotta.Use of corticosteroids,other immunosuppressive therapiesand tonsillectomy in the treatment of IgA nephropathy[J] .Semin Nephro1.2004,24(3):244—55.
    62. DRmico G.Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome[J].Semin Nephro1.2O04,24(3):179-96.
    63. Efstathios Alexopoulos. Treatmentofprimary IgA nephropathy. [J].KidneyInt, 2004,65(1):341—55.
    64.房向东,杨丽萍,黄天伦.24例IgA肾病肾小管间质损害的临床与病理[J].中国现代医学杂志, 2007,17(8):999-1001.
    65.陈洪滔,许慧丽,廖莹,等. IgA肾病肾小管间质病变与临床及病理的关系[J].临床内科杂志,2007,24(5):319-321.
    66.陈香美.肾小球疾病中肾小管间质损害的研究进展[J].中华肾脏病杂志,2002,4,18(2);146-147.
    67. Masaaki Eiro, et al. The Product of Duration and Amount of Proteinuria (Proteinuia Index)Is a Possible Marker for Glomerular and Tubulointerstitia Damage in IgA Nephropathy[J]. Nephron, 2002,90:432-441.
    68.陈孝文,刘华锋.从肾小管-间质纤维化发病机制探讨其中西医结合防治新策略[J].中国中西医结合肾病杂志,2008,9(1):1-4.
    69.赵宗江,仇琪.核转录因子κB在肾间质纤维化中的作用[J].中国中西医结合肾病杂志,2006,7(10):610-612.
    70.周桂琴,张磊,吴巍,等.膜联蛋白-1和巨噬细胞移动抑制因子在IgA肾病模型与人IgA肾病肾组织中的表达及其意义[J].中国全科医学,2008,11(4A):574-576.
    71.柯颖杰,林曦,吴光华,等.结缔组织生长因子在IgA肾病肾间质纤维化中的表达及意义[J].浙江临床医学,2006,8(2):116-117.
    72.汤询,袁发焕.金属蛋白酶组织抑制因子一1、基质金蛋白酶-9的表达与肾脏纤维化的关系[J].中国现代医学杂志,2002,12(2):13-15
    73.董健平,陈香美,冯全洲等.反义金属蛋白酶组织抑制剂-1对大鼠肾小管间质损害的治疗作用[J].中华医学杂志,2002,8(2),617-621.
    74. LeungJC,Chan LY,Tsang AW,et al.Anti-macrophage migration mhibitory factor reduces transforming growth factor-beta 1 expression in experimental IgA nephropathy. Nephrol Dial Transplant,2004,19(8):1976-1985.
    75.马云,白芸,侯连兵.核转录因子-κB与肾脏疾病研究进展[J].实用医学杂志,2006,22(5):603-605.
    76.祁中华,林善谈,黄宇峰.黄芪改善糖尿病早期肾血流动力学异常的研究[J].中国糖尿病杂志,1999,7(3):147一149.
    77.彭卫华,曲强.黄芪治疗肾脏疾病的现代药理研究[J].中国中西医结合肾病杂志2001,2(10):614-616.
    78.黄文政.肾脏病中医药现代研究的若干进展[J].中国中西医结合肾病杂志, 2003,4(8):487-490.
    79.查良伦,沈自尹,张晓峰,等.生地对家兔糖皮质激素受抑模型的实验研究[J].中西医结合杂志,1988,8(2):22.
    80.马健,等.生地黄对阴虚模型小鼠腹腔巨噬细胞Ia抗原表达的影响[J].中药药理与临床,1998,14(2):22.
    81.贺玉琢,等.日本对地黄的研究[J].国外医学?中医中药分册,1997,19(4):13.
    82.王浴生主编.中药药理与应用[M].第1版.北京:人民卫生出版社,1983:400.
    83.黄泰康主编.常用中药成分与药理手册[M].第1版.北京:中国医药科技出版社. 1994, 797.
    84.高学敏主编.中药学[M].第1版.北京:人民卫生出版社,2000,1741.
    85.苗明三,孙艳红,方晓艳.(怀)熟地黄多糖抗氧化作用[J].中国中医药信息杂志,2002,9(10):32-33.
    86.董昆山主编.现代临床中药学[M].第1版.中国中医药出版社,1998, 533.
    87.阴健主编.中药现代研究与临床应用[M].第1版.北京:人民卫生出版社,1994,551.
    88.全红,周涛,等.白茅根的研究概况[J].中医药学报, 1999,(l):6l .
    89.胡慧娟,周德荣,等.旱莲草的抗炎作用及机制研究[J].中国药科大学学报, 1995,26(4):226一229
    90.田代华主编.实用中药词典[M].第1版.北京:人民卫生出版社,2003, 2017.
    91.杜中惠,宋健,刘东升.阿胶现代研究与应用[J].时珍国医国药,1999,10(4):297.
    92.曾万玲,宋杰云,芩燕飞.地榆水煎液抗实验性腹泻及其他药理作用研究[J].贵阳中医学院学报,1992,14(4):55.
    93.浙江医学院附属二院内科学血液学实验室.小蓟凝血作用的实验研究[J].哲医通讯,1975,(5):22.
    94.梁统,覃燕梅,梁念慈.侧柏叶醇提取物抗炎作用的研究[J].中国药科大学学报,2001,32(3):224-226.
    95.阮金兰,赵钟祥,曾庆忠.赤芍化学成分和药理作用的研究进展[J].中国药理学通报,2003,19(9):965-970.
    96.聂莉芳,于大君,王洪霞等.益气滋肾冲剂治疗IgA肾病100例临床观察[J].中医杂志,2002,43(11):843-844.
    97.陈强,胡伟新,王生余,等.尿视黄醇结合蛋白判断肾小管-间质损伤的临床意义[J].肾脏病与透析肾移植杂志,2001,10(5):406-470.
    98. Calandra T, Roger T. Macrophage migration inhibitory factor: aregulator of innate immunity[J]. Nat Rev Immuno,l 2003, 3 (10): 791-800.
    99. Morand E F, LeechM, Bernhagen J. MIF: a new cytokine linkbetween rheumatoid arthritis and atherosclerosis[J]. Nat RevDrugDiscov, 2006, 5(5): 399-410.
    100. Sasaki S , Nishihira J , Ishibashi T , et al. Transgene of MIF induces podocyte injury and progressive mesangial sclerosis in the mouse kidney. Kidney Int , 2004,65:469-481.
    101. Rice E K, Tesch G H, Cao Z,et al. Induction ofMIF synthesis and secretion by tubular epithelial cells: a novel action of angio-tensinⅡ[J]. Kidney Int, 2003, 63(4): 1265-1275.
    102. Sasaki S, Nishihira J, Ishibashi T,et al. Transgene ofMIF in-duces podocyte injury and progressive mesangial sclerosis in themouse kidney[J]. Kidney Int, 2004, 65(2): 469-481.
    103. Leung JC, ChanLY, TsangAW,etal. Anti-macrophage migration inhibitory factor reduces transforming growth factor-beta 1 expression in experimental IgA nephropathy [J]. Nephrol DialTransplant, 2004, 19(8): 1976-1985.
    104.周进学.叶启发.明英姿.等.三七总皂甙对移植肝缺血再灌注后核因子κB、ICAM -1表达的影响[J].中国现代医学杂志.2005,15(9): 1330-1333.
    105.姜玉姬,陈瑛,李灿.NF-κB在IgA肾病中的表达及意义[J]。山东医药.2008,48(41):100-102.

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