益肾通络法对糖尿病周围神经病变治疗作用的理论及实验研究
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摘要
背景:糖尿病周围神经病变(DPN)是糖尿病患者常见的并发症,其发病趋势在不断增长,可累及感觉神经,运动神经及植物神经,产生肢体麻木疼痛、运动障碍,肌肉萎缩甚至痿废失用和植物神经功能障碍。其发病机制至今未明,亦缺乏特异性的治疗方法及药物。近年来随着糖尿病及其并发症基础研究的进展,对糖尿病神经病变的发病机制有了较深入的认识,有血管、代谢、神经生长因子、自身免疫及炎症等诸多因素,且这些因素共同作用相互影响,为寻找针对性的药物提供了理论基础和依据。
     目的:本研究探讨糖尿病周围神经病变的中医病理机制,指出肾阴亏虚,络脉瘀阻是DPN的主要病理机制,制定益肾通络的治疗法则,旨在验证益肾通络法的中药方剂防治糖尿病周围神经病变的作用,并探讨其对糖尿病周围神经病变防治作用的机制,提供药物临床应用的理论依据,为中药防治糖尿病神经病变提供新的研究思路。
     方法:以链脲佐菌素(STZ)诱发糖尿病模型大鼠,成模后,分正常组、模型组、阳性对照组(弥可保)、中药小剂量组、大剂量组,治疗10周后,观察中药复方对模型大鼠血糖、体重、SOD、MDA、NO、NOS、NGF含量的影响,并对治疗后的实验性糖尿病大鼠坐骨神经组织进行病理学检查。
     结果:经益肾通络治疗后的糖尿病大鼠的体重升高,血糖降低,血清SOD的含量明显增多,MDA的含量明显降低,血清NO、NOS含量明显降低,血清NGF含量明显升高,AGEs含量减少,与模型组比较有显著差异。通过形态学观察,该药对坐骨神经的也有保护作用。
     结论:1、本文在前人关于消渴病病机及治疗论述基础上,提出糖尿病周围神经病变的中医病机主要为肾阴亏虚、络脉瘀阻,制定了益肾养阴、活血通络的治疗法则和方药。2、实验研究发现益肾通络的中药可明显减轻糖尿病周围神经病变的程度,对糖尿病周围神经病变有明显治疗作用,而且随着药物浓度的增高,治疗作用越明显。
Background: With an increasing incidence, diabetic peripheral neuropathy(DPN) is one of the most common complications of diabetes mellitus. It is related to the function loss of sensory, motor, autonomic nerve exhibiting numbness, soreness, dyscinesia, muscular atrophy even paralyzed and autonomic nerve dysfunction. Its pathogenesis is still unknown so far, but also the specific therapy and drug are lack. In recent years, with diabetes and its complications in the progress of basic research, the pathogenesis of diabetic neuropathy mechanisms have a more in-depth understanding. Several mechanisms may play an important role leading to the disturbance and have an interaction: vascular, metabolism, nerve growth factor, autoimmune and inflammation. It contributes to seek therapies and effective drugs for diabetic neuropathy. Objective: To discuss the pathology mechanism of traditional Chinese medicine in diabetic peripheral neuropathy, point out that deficiency of kidney yin, blood stagnation in collateral is the major pathology mechanism of DPN, establish kidney-nourishing and collateral-activating therapy , study the effect of traditional Chinese medicine by kidney-nourishing and collateral-activating therapy on DPN, discuss the protective and therapeutic mechanisms of the therapy for peripheral neuropathy in experimental diabetic rats, establish the foundation of clinical application and provide new research clues of prevention on DPN with traditional Chinese medicine.
     Methods: The rats model of diabetes were induced by streptozotocin. The rats were randomly divided into normal control group, model group, positive control group (Methycobal), low dose of traditional Chinese medicine treated group, high dose of traditional Chinese medicine treated group. To observe the effect of kidney-nourishing and collateral-activating therapy on blood glucose, body weight, SOD, MDA, NO, NOS, NGF, content from rat serum after 10 weeks, and experimental diabetic rat sciatic nerve pathology organizations.
     Results: Compareed with model group, the content of blood glucose, MDA, NO, NOS, AGEs in serum of rats of traditional Chinese medicine treated group were significantly decreased, body weight, SOD, NGF content were significantly increased. By observing the morphology of the sciatic nerve, the drug also has a protective effect on the nerve.
     Conclusion: 1、We study forefathers about Xiaokezheng on machine and treatment exposition foundation, point out that deficiency of kidney yin and blood stagnation in collateral were the pathology mechanism of traditional Chinese medicine of DPN, which have established kidney-nourishing and collateral-activating therapy with the prescription of traditional Chinese medicine.
     2、Experiment study found that traditional Chinese medicine of kidney-nourishing and collateral-activating therapy can alleviate obviously the degree of diabetic peripheral neuropathy. And for diabetic peripheral neuropathy, it has obvious therapeutic effect, and along with increased drug concentration, therapeutic effect is the more obvious.
引文
[1]程汉桥,魏子孝.消渴病历代中医文献理论研究[J].山东中医杂志200l,20(12):707-708
    [2]周庆伟,宗瑞义,谢湘林,等.天芪胶囊降糖作用的实验研究[J].中草药,1997,28(2):95-97
    [3]冯德华.六味地黄制剂药理及临床应用进展[J].中医药研究,2000,16(1):55-56
    [4]吴晋兰.糖尿病从脾论治初探[J].浙江中医学院学报,1998,22(3):18
    [5]倪海祥.从肝论治2型糖尿病的临床研究[J].中国中西医结合杂志,2000,20(8):577-579
    [6]时梅莉.复元活血汤在糖尿病中的应用[J].河南中医,2003,23(12):71
    [7]林东平,杨裕国.糖尿病患者血小板活化状态和纤溶活性的变化[J].实用医学杂志,1999,15(6):425-426
    [8]衡先培,王善慧等.糖络通对DNP大鼠血液流变性的影响[J].安徽中医学院学报,2002,21(5):42-44
    [9]许成群.糖尿病周围神经病变的中医病机探讨[J].现代中医药,2003,(4):55-56
    [10]许成群.糖尿病周围神经病变的中医病机探讨[J].现代中医药,2003,(4):55-56
    [11]张宏亮.辨证治疗糖尿病周围神经病变58例[J].河南实用神经疾病杂志,2001,4(3):37-38
    [12]孙春英.益气活血法治疗糖尿病周围神经病变30例[J].江苏中医,2000,2l(12):24-25
    [13]马颖,鲍淑娟.自拟活络汤治疗糖尿病周围神经病变(DNP)观察[J].中国社区医师,2007,9(174):114
    [14]童蓓丽,王瑞芳等.活血通痹汤治疗糖尿病周围神经病变56例疗效观察[J].河北中医,2006,28(7):492-493
    [15]缪卫华,余江毅等.通痹方治疗糖尿病周围神经病变64例效果观察[J].交通医学,2007,21(6):675-676
    [16]吴春明.益气活血祛瘀法治疗糖尿病周围神经病变32例[J].湖南中医杂志,2003,19(6):34-35
    [17]金杰,陈海燕等.中药糖脉通片治疗糖尿病周围神经病临床研究[J].河南中医,2003,23(12):19-21
    [18]潘继兵.化痰逐瘀法治疗糖尿病周围神经病变的临床观察[J].北京中医杂志,2002,(3):161
    [19]段红莉.痰瘀并治法治疗糖尿病性周围神经病变36例[J].陕西中医,2006,27(3):284-285
    [20]李萍.益气养阴活血通络汤治疗糖尿病周围神经病变80例[J].四川中医,2004,22(4):44
    [21]郑姜钦,李红等.滋阴益气活血法治疗糖尿病周围神经病变48例[J].福建中医学院学报,2007,17(6):10-11
    [22]陈华.益气养阴活血方治疗糖尿病周围神经病变68例[J].新中医,2006,38(11):62-63
    [23]刘华.益肾补阳还五汤治疗糖尿病周围神经病变[J].浙江中西医结合杂志,2003,13(9):534-536
    [24]罗试计.补肾活血通络法治疗糖尿病周围神经病变临床研究[J].辽宁中医药大学学报,2007,9(6):116-117
    [25]郑敏,杨宏杰等.温肾化瘀通络法治疗糖尿病周围神经病变60例临床观察[J].江西中医药,2004,35(263):20-21
    [26]牟淑敏,张宁宁等.益气养阴活血法对糖尿病大鼠自主神经功能的影响[J].山东中医杂志,2008,27(7):485-487
    [27]房玉娥,邓德强等.化痰通络法治疗糖尿病周围神经病变[J].中外健康文摘,2008,6:78-79
    [28]张云云,刘笑迎.活血化瘀在糖尿病周围神经病变中的应用[J].辽宁中医药大学学报,2008,10(2):6-7
    [29]李先荣.黄芪多糖冲剂治疗Ⅱ型糖尿病的临床研究[J].山西中医,1995,11(9):32-34
    [30]党海霞.黄芪治疗糖尿病的药理研究近况[J].中国药学报,2000,30(3):69-71
    [31]祈忠华,林善镁等.黄芪改善糖尿病肾病早期血流动力学异常的研究[J].中国糖尿病杂志,1997,7(3):147-149
    [32]鲁瑾,邹大进,张家庆.黄芪预防肿瘤坏死因子-α所致胰岛素抵抗[J].中国中西医结合杂志,1999,19(7):420-422
    [33]Vinik AL,Park TS,Stansberry KB.Diabetic neuropathies[J].Din-betologia,2000,43:957-973
    [34]Adnot S,Raffestin B,Eddahibi S.NO in lung[J].Respir Physiol,1995,101(1):109-120
    [35]陈群,刘景丰.糖尿病大鼠血清一氧化氮和一氧化氮合酶的变化及意义[J].福建医科大学学报,2005,39(4):390-391
    [36]Hounsom L,Tomlinson DR.Does neuropathy develop in animal models?Clin N eurosci 1997;4(6):380-389
    [37]Medri R,Antilio-Gambetti L,Jenich H,Gambetti P.Changes in axon size and slow axonal transport are related in experimental diabetic neuropathy.Neurology.1988;38:597-601
    [38]Yagihashi S,Kamijo M,Watanabe K.Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats.Am J Pathol.1990;136:1365-1373
    [39]Russul JW,Windebank AJ,Schenone A,Feldman EL.Insulin-like growth factor-1 prevents apoptosis in neurons after growth factor withdrawal.J Neurobiol.1998;36:455-467
    [40]Yagihashi S.Pathology and pathogenetic mechanisms of diabetic neuropathy.Diab Metab Rev.1995;11:193-220
    [41]Chakrabarti S,Zhang Wx,Sima AAF.Optic neuropathy in the diabetic BB-rat.Adv Exp Med Biol.1991;291:257-264
    [42]Yagihashi S,Wada RI,Kamijo M,Nagai K.Peripheral neuropathy in the WBN/Kob rat withchronic pancreatitis and spontaneous diabetes.Lab Invest.1993;68:296-307
    [43]Sima AAF,Subimoto K,Experimental diabetic neuropathy:an update.Diabetologia.1999;42:773-788
    [44]Head RJ,McLennan PL,Raederstorff D,Muggli R,Bumard SL,McMurchie EJ.prevention of nerve conduction deficit in diabetic rats by polyunsaturated fatty acids.Am J Clin Nutr 2000;71(suppl):386s-392s
    [45]Calcutt NA,Freshwater JD,O' Brien JS.Prtection of sensory fuction and antihyperalgesic properties of prosaposin-derived peptide in diabetic rats.Anesthesiology,2000;95(5):1271-8
    [46]张英锋,裴中会,阮栋梁.SOD-一种超氧化物歧化酶[J].化学世界,2004,45(2):112
    [47]叶和杨,周俐,曾靖,等.金边瑞香对小鼠SOD活性及MDA含量的影响[J].赣南医学院学报,2003,23(3):246-248
    [48]许成群.活血化瘀治疗糖尿病机理[J].陕西中医学院学报,2001,2(4):13-15
    [49]Apfel SC.Nerve growth factor for the treatment of diabetic neuropathy:what went wrong,what went right,and what does the future hold?Int Rev Neurobiol.2002,50:393-413
    [50]Sima AAF,Zhang W,Xu G,Sugimoto K,Guberski D,Yorek MA.A comparison of diabetic polyneuropathy in type Ⅱ diabetic BBZDR/Wor rats and in type Ⅰ diabetic BB/Wor rats.Diabetologia.2003;43:786-793
    [51]YagihashiS,Kamijo M,Watanabe K.Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats.Am J Pathol.1990;136:1365-1373
    [52]林东平,杨裕国.糖尿病患者血小板活化状态和纤溶活性的变化[J].实用医学杂志,1999,15(6):425-426
    [53]许成群.糖尿病周围神经病变的中医病机探讨[J].现代中医药,2003,(4):55-56
    [54]许成群.糖尿病周围神经病变的中医病机探讨[J].现代中医药,2003,(4):55-56
    [55]张宏亮.辨证治疗糖尿病周围神经病变58例[J].河南实用神经疾病杂志,2001,4(3):37-38
    [56]孙春英.益气活血法治疗糖尿病周围神经病变30例[J].江苏中医,2000,21(12):24-25
    [57]马颖,鲍淑娟.自拟活络汤治疗糖尿病周围神经病变(DNP)观察[J].中国社区医师,2007,9(174):114
    [58]童蓓丽,王瑞芳等.活血通痹汤治疗糖尿病周围神经病变56例疗效观察[J].河北中医,2006,28(7):492-493
    [59]缪卫华,余江毅等.通痹方治疗糖尿病周围神经病变64例效果观察[J].交通医学,2007,21(6):675-676
    [60]吴春明.益气活血祛瘀法治疗糖尿病周围神经病变32例[J].湖南中医杂志,2003,19(6):34-35
    [61]金杰,陈海燕等.中药糖脉通片治疗糖尿病周围神经病临床研究[J].河南中医,2003,23(12):19-21
    [62]潘继兵.化痰逐瘀法治疗糖尿病周围神经病变的临床观察[J].北京中医杂志,2002,(3):161
    [63]段红莉.痰瘀并治法治疗糖尿病性周围神经病变36例[J].陕西中医,2006,27(3):284-285
    [64]李萍.益气养阴活血通络汤治疗糖尿病周围神经病变80例[J].四川中医,2004,22(4):44
    [65]郑姜钦,李红等.滋阴益气活血法治疗糖尿病周围神经病变48例[J].福建中医学院学报,2007,17(6):10-11
    [66]陈华.益气养阴活血方治疗糖尿病周围神经病变68例[J].新中医,2006,38(11):62-63
    [67]刘华.益肾补阳还五汤治疗糖尿病周围神经病变[J].浙江中西医结合杂志,2003,13(9):534-536
    [68]罗试计.补肾活血通络法治疗糖尿病周围神经病变临床研究[J].辽宁中医药大学学报,2007,9(6):116-117
    [69]郑敏,杨宏杰等.温肾化瘀通络法治疗糖尿病周围神经病变60例临床观察[J].江西中医药,2004,35(263):20-21
    [70]曾庆德.葛根素治疗2型糖尿病并发周围神经病变80例疗效观察[J].实用中西医结合临床,2006,6(6):53-54
    [71]丁方,石凤英等.葛根素对去卵巢鼠糖尿病肾病及周围神经病变的作用[J].复旦学报(医学版),2006,33(6):871-872
    [72]马松涛,王秋林等.桑白皮提取物对糖尿病大鼠坐骨神经传导速度及生化功能的影响[J].中国药房,2007,18(3):174-176
    [73]马松涛,张效科.桑白皮提取物对糖尿病大鼠神经生长因子、碱性髓鞘蛋白表达的影响[J].中国中医基础医学杂志,2007,13(10):760-763
    [74]张艳荣.血栓通治疗糖尿病周围神经病变疗效观察[J].临床和实验医学杂志,2005,4(3):163-165
    [75]侯英,刘静等.灯盏花素治疗糖尿病周围神经病变的疗效观察[J].黑龙江医药,2003,3(27):208-209
    [76]刘福来,阎英杰等.灯盏花素治疗糖尿病周围神经病变60例疗效观察[J].时珍国医国药,2006,17(11):2286-2287
    [77]廉治军,徐金明.透刺治疗糖尿病周围神经病变41例分析[J].中医药学刊,2004,22(4):725
    [78]杨莉.针灸治疗糖尿病性周围神经病变疗效观察[J].四川中医,2003,21(2):77
    [79]杨莉.针灸治疗糖尿病周围神经病变疗效观察[J].四川中医,2003,21(2):77
    [80]姜鹤群,施宽德等.腕踝针疗法治疗糖尿病末梢神经炎30例临床研究[J].中医杂志,2005,46(1):21
    [81]储小红,虞华等.中药薰洗辅助治疗糖尿病性周围神经病变的疗效观察[J].护理实践与研究 2006,3(4):54-55
    [82]徐玉梅,刘燕平等.温经通络熏洗方治疗糖尿病周围神经病变的疗效观察及护理[J].齐鲁护理杂志,2006,12(6):1039-1040
    [83]中华医学会糖尿病学分会.中国糖尿病防治指南(试行本)北京:北京大学医学出版社,2004.52
    [84]刘欣,康德萱.糖尿病神经病变发生机制研究的若干进展.国外医学神经.病学神经外科学分册.2001,28(3):201
    [85]Sima AA,Sugimoto K.Experimental diabetic neuropathy:an update[J].Diabetologia,1999,42(7):773
    [86]Oates PJ.Polyol pathway and diabetic peripheral neuropathy[J].Int Rev Neurobiol,2002,50:325
    [87]Vinik A、Diabetic neuropathy:Pathogenesis and therapy[J].Am J Med,1999,107(2):117
    [88]Apfel SC.Nerve growth factor for the treatment of diabetic neuropathy:what went wrong,what went right,and what does the future hold?Int Rev Neurobiol.2002,50:393-413
    [89]李红,张曼云.胰岛素样生长因子-1与糖尿病周围神经病变的关系[J].河北医学,2001,7(10):893-896
    [90]Sayers NM,Beswick L J,Middlemas A,et al.Neurotrophin-3 prevents the proximal accumulation of neurofilament proteins in sensory neurons of streptozocin-induced diabetic rats[J].Diabetes,2003,52(9):2372
    [91]施晓红,周湘兰.糖尿病周围神经病变与血液流变学相关性分析[J].中国临床医学,2004,11(4):502-503
    [92]Cameron NE.Eaton SE.Cotter MA,et al Vascular factors and metabolic interactbns in the pathogenesis of diabetic neuropathy[J].Disbetologia,2001,44:1973-1988
    [93]Vinik AL.Park TS,Stansberry KB.Diabetic neuropathies[J].Din-betologia,2000,43:957-973
    [94]Zhu XP,Zhou ZG.Clinical observation of combined therapeutic effect of prostaglandin E1 and mecobalamin on diabetic peripheral neuropathy[J].Hunan Yi Ke Da Xue Xue Bao,2001,26(4):343
    [95]郭志新,任桂卿.血管紧张素转换酶和内皮素与糖尿病微血管病变的关系[J].中国全科医生,2001,4(6):443
    [96]周微雅,李妮等.糖尿病周围神经病变IL-1B及TNF-a的介导作用[J].中国免疫学杂志,2003,9:655
    [97]Oates PJ.Polyol pathway and diabetic peripheral neuropathy[J].IntRevNeurobiol 2002;50:325-392
    [98]卫重娟,程炎,梁浩.醛糖还原酶抑制剂对实验性糖尿病周围神经病大鼠内源性NGF及神经肽的影响[J].中风与神经疾病杂志,2003,20(6):516-518
    [99]罗邦尧,赵咏桔,陈宇红等.依帕司他治疗糖尿病周围神经病变有效性和安全性的临床研究[J].继续医学教育,2005,19(1):58-60
    [100]蔡明江,成杰.糖尿病痛性神经病变的治疗[J].临床荟萃,2001;16(23):1071
    [101]张云云,苏雅茹,杨莉芹.人神经生长因子治疗糖尿病性多发性神经病的随机双盲研究[J].中国临床神经科学,2003,11(1):67-70
    [102]车玉琴,高杰,张福宏.甲钴胺对糖尿病周围神经病变患者神经传导速度的影响[J].中国医科大学学报,2005,34(5):493
    [103]李顺勇,杨亚韶.高压氧治疗糖尿病周围神经病变的临床观察[J].临床荟萃,2003,18(13):755-756
    [104]戚筠,石晓建.光量子氧透射液体疗法治疗糖尿病末梢神经病变疗效观察[J].临床荟萃,2001;16(22):1025

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