通络糖泰方对糖尿病周围神经病变大鼠炎性细胞因子的影响
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摘要
【目的】探讨通络糖泰方对糖尿病周围神经病变(DPN)大鼠炎性细胞因子的影响。【方法】选用自发性2型糖尿病GK大鼠,建立由高脂饲料喂养的DPN大鼠模型,随机分为5组:模型组,通络糖泰方高、中、低剂量组(剂量分别为2.88、1.44、0.72 g·kg~(-1)·d~(-1)),西药组(100 mg·kg~(-1)·d~(-1)二甲双胍+0.2 mg·kg~(-1)·d~(-1)弥可保)。并选用Wistar大鼠设为正常组。分别给予相应处理4周后采用神经电生理检测大鼠坐骨神经运动/感觉神经传导速度;采用酶联免疫吸附试验检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、髓鞘碱性蛋白(MBP)水平。【结果】通络糖泰各剂量组可降低血清炎性细胞因子水平,降低血清MBP水平,提高坐骨神经传导速度,其中高剂量组作用最显著。【结论】通络糖泰方可减轻炎症反应,减少神经脱髓鞘病变,改善神经结构和传导功能,从而达到防治DPN发生发展的作用。
Objective To investigate the effect of Tongluo Tangtai Recipe(TTR)on inflammatory cytokines in rats with diabetic peripheral neuropathy(DPN). Methods Rat model of spontaneous DPN was established by feeding high fat diet. The rats were divided into 5 groups, namely model group, western medicine(metformin 100mg·kg-1·d-1+ methycobal 0.2 mg·kg-1·d-1)group,and low-,middle- and high-dose TTR groups(TTR in the dosage of 0.72,1.44,2.88 g·kg-1·d-1 respectively). Rats of the normal group and model group were treated with normal saline orally, and the medication groups were given the corresponding medicine according to the experimental design. After intragastric administration for 4 weeks, sciatic motor/sensory nerve conduction velocity was detected with electrophysiological examination method,and tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),C-reactive protein(CRP),myelin basic protein(MBP)levels in the serum were examined by enzyme-linked immunosorbent assay(ELISA). Results TTR in various dosages could reduce the serum levels of MBP and inflammatory cytokines of TNF-α,IL-6 and CRP,and increase sciatic nerve conduction velocity(P <0.05 or P <0.01 compared with those in the model group), the high dose showing the strongest effect.Conclusion TTR could inhibit inflammation reaction and nerve demyelination,and improve nerve structure and conduction function,which may contribute to the preventive and therapeutic mechanism of TTR for DPN.
Objective To investigate the effect of Tongluo Tangtai Recipe(TTR)on inflammatory cytokines in rats with diabetic peripheral neuropathy(DPN). Methods Rat model of spontaneous DPN was established by feeding high fat diet. The rats were divided into 5 groups, namely model group, western medicine(metformin 100mg·kg-1·d-1+ methycobal 0.2 mg·kg-1·d-1)group,and low-,middle- and high-dose TTR groups(TTR in the dosage of 0.72,1.44,2.88 g·kg-1·d-1 respectively). Rats of the normal group and model group were treated with normal saline orally, and the medication groups were given the corresponding medicine according to the experimental design. After intragastric administration for 4 weeks, sciatic motor/sensory nerve conduction velocity was detected with electrophysiological examination method,and tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),C-reactive protein(CRP),myelin basic protein(MBP)levels in the serum were examined by enzyme-linked immunosorbent assay(ELISA). Results TTR in various dosages could reduce the serum levels of MBP and inflammatory cytokines of TNF-α,IL-6 and CRP,and increase sciatic nerve conduction velocity(P <0.05 or P <0.01 compared with those in the model group), the high dose showing the strongest effect.Conclusion TTR could inhibit inflammation reaction and nerve demyelination,and improve nerve structure and conduction function,which may contribute to the preventive and therapeutic mechanism of TTR for DPN.
引文
[1]郑昌健,胡涵,曹红,等.JNK/MCP-1信号通路在姜黄素抗糖尿病神经病理性疼痛中的作用[J].中国病理生理杂志,2014,30(11):1941.
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[12]俞丽凝,杨晓苏,华赞,等.糖尿病周围神经痛患者血清促炎细胞因子水平的相关性研究[J].中华中医药杂志,2009,89(7):469.
[13]施晓红,周连华,李益明.细胞因子与2型糖尿病周围神经病变的相关性研究[J].神经疾病与精神卫生,2012,12(1):27.
[14]余传霖,叶天星,陈德源,等.现代医学免疫学[M].上海:上海医科大学出版社,1998:386.
[15]Gonzalez-Clemente J M,Mauricio D,Richart C,et al.Diabetic neuropathy is associated with activation of the TNF-alpha system in subjects with type 1 diabetes mellitus[J].Clin Endocrinol(Oxf),2005,63(5):525.
[16]王庆松,陈曼娥.髓鞘碱性蛋白与中枢神经系统损害[J].国外医学:神经病学神经外科学分册,1995,22(6):306.
[17]Warren K G,Catz I.An extensive search for autoantibodies to myelin basic protein in cerebrospinal fluid of non-multiplesclerosis proteins:implications for the pathogenesis of multiple sclerosis[J].Eur Neurol,1999,42(2):95.
[18]Becker K J,Mc Carron R M,Ruetzler C,et al.Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia[J].Proc Natl Acad Sci USA,1997,94(20):10873.
[19]王明选.通络糖泰方对糖尿病周围神经病变大鼠血清肿瘤坏死因子-α影响的实验研究[D].成都:成都中医药大学,2008.
[20]王丽英,张红敏,谢春光,等.中医释义动脉粥样硬化及2型糖尿病低度炎症的发生条件[J].时珍国医国药,2005,16(7):662.
[2]Goldberg R B.Cytokine and cytokine-like inflammation markers,endothelial dysfunction,and imbalanced coagulation in development of diabetes and its complications[J].Clin Endocrinol Metab,2009,94:3171.
[3]Doupis J,Lyons T E,Wu S,et al.Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy[J].J Clin Endocrinol Metab,2009,94:2157.
[4]Pabreja K,Dua K,sharma S,et al.Minocycline attenuates the development of diabetic neuropathic pain:Possible antiinflammatory and anti-oxidant mechanisms[J].Eur J Pharmacol,2011,661:15.
[5]罗茂林,谢春光,张云飞.糖尿病周围神经病变中医药研究进展[J].辽宁中医杂志,2005,32(6):617.
[6]张海生,谢春光.通络糖泰方对糖尿病神经病变大鼠血清C反应蛋白水平及神经功能的影响[J].中医临床研究,2009,1(1):51.
[7]杜联,殷丽平,王晓娟,等.通络糖泰方对糖尿病周围神经病变大鼠血清肿瘤坏死因子-α水平的影响[J].中药药理与临床,2010,26(3):53.
[8]杜锐玲,张海生,谢春光.通络糖泰方对糖尿病周围神经病变大鼠神经传导速度的影响[J].中华实用中西医杂志,2007,14(20):1230.
[9]Said G,Lacmix C,Lozeron P,et al.Infammatory vasculopathy in muhifocal diabetic neuropathy[J].Brain,2003,126(2):376.
[10]Cameron N E,Eaton S E,Cotter M A,et al.Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy[J].Diabetologia,2001,44(11):1973.
[11]张海生.通络糖泰方对糖尿病神经病变大鼠血清C反应蛋白水平及神经功能的影响[D].成都:成都中医药大学,2006.
[12]俞丽凝,杨晓苏,华赞,等.糖尿病周围神经痛患者血清促炎细胞因子水平的相关性研究[J].中华中医药杂志,2009,89(7):469.
[13]施晓红,周连华,李益明.细胞因子与2型糖尿病周围神经病变的相关性研究[J].神经疾病与精神卫生,2012,12(1):27.
[14]余传霖,叶天星,陈德源,等.现代医学免疫学[M].上海:上海医科大学出版社,1998:386.
[15]Gonzalez-Clemente J M,Mauricio D,Richart C,et al.Diabetic neuropathy is associated with activation of the TNF-alpha system in subjects with type 1 diabetes mellitus[J].Clin Endocrinol(Oxf),2005,63(5):525.
[16]王庆松,陈曼娥.髓鞘碱性蛋白与中枢神经系统损害[J].国外医学:神经病学神经外科学分册,1995,22(6):306.
[17]Warren K G,Catz I.An extensive search for autoantibodies to myelin basic protein in cerebrospinal fluid of non-multiplesclerosis proteins:implications for the pathogenesis of multiple sclerosis[J].Eur Neurol,1999,42(2):95.
[18]Becker K J,Mc Carron R M,Ruetzler C,et al.Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia[J].Proc Natl Acad Sci USA,1997,94(20):10873.
[19]王明选.通络糖泰方对糖尿病周围神经病变大鼠血清肿瘤坏死因子-α影响的实验研究[D].成都:成都中医药大学,2008.
[20]王丽英,张红敏,谢春光,等.中医释义动脉粥样硬化及2型糖尿病低度炎症的发生条件[J].时珍国医国药,2005,16(7):662.