温控TRP与阳虚质膝骨关节炎关系探讨
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摘要
随着人口老龄化的加剧,近年来膝骨关节炎(KOA)的发病率急增。目前临床治疗KOA以西药为主流药物,但其存在不良反应大,停药后易复发等缺陷。越来越多的文献显示,我国传统中医药在KOA的治疗上具有较好的疗效,较西药更为安全,因此日益受到人们关注。据研究阳虚质人易患KOA,可能与其自身对外环境某些变化因子较为敏感有关。温控瞬时受体电位通道(TRP)为一种Ca~(2+)离子通道,不同温度能够激活各自相应通道,尽管目前对这类通道与温度的关系有一定的认识,但阳虚质人易患KOA的现象与TRP的开闭异常是否存在联系,现仍不明确。文章就KOA的症状和治疗用药与TRP的关系进行分析综述,为进一步研究预防KOA的药物提供理论基础和选药参考。
With the aging of the population intensifying,the incidence of knee osteoarthritis(KOA) is increasing in the recently years.Modern medications become current clinical treatment of KOA.However,most of these drugs showed disadvantages,including multiple side-effects efficiency and high rate of relapse.More and more literature shows that Chinese herbal medicine has a potential therapeutic effect and is safer for the treatment of KOA.Studies have shown that patients with Yang-deficiency constitution are susceptible to KOA.This because their bodies are sensitive to the environmental changes.The transient receptor potential(TRP) is Ca~(2+)-permeable cation channel that serves as a sensor of thermal or osmotic signals.These channels can be activated by different corresponding temperatures.But the relationships between TRP channels and KOA with the patients of Yang-deficiency constitution are not clear.This review summarized the relations of symptoms,treatment of KOA with Yang-deficiency and TRP,which provided a theoretical basis and choice for the further exploration drugs for KOA prevention.
With the aging of the population intensifying,the incidence of knee osteoarthritis(KOA) is increasing in the recently years.Modern medications become current clinical treatment of KOA.However,most of these drugs showed disadvantages,including multiple side-effects efficiency and high rate of relapse.More and more literature shows that Chinese herbal medicine has a potential therapeutic effect and is safer for the treatment of KOA.Studies have shown that patients with Yang-deficiency constitution are susceptible to KOA.This because their bodies are sensitive to the environmental changes.The transient receptor potential(TRP) is Ca~(2+)-permeable cation channel that serves as a sensor of thermal or osmotic signals.These channels can be activated by different corresponding temperatures.But the relationships between TRP channels and KOA with the patients of Yang-deficiency constitution are not clear.This review summarized the relations of symptoms,treatment of KOA with Yang-deficiency and TRP,which provided a theoretical basis and choice for the further exploration drugs for KOA prevention.
引文
[1] 吕苏梅,张瑞丽.中老年膝骨关节炎的流行病学研究进展[J].中国老年学杂志,2016,36(16):4133-4135.
[2] 王琦.9种基本中医体质类型的分类及其诊断表述依据[J].北京中医药大学学报,2005,28(4):1-8.
[3] 何栩,罗小兵,虞亚明,等.中老年女性膝骨关节炎患者中医体质类型特点的初步探讨[J].中医正骨,2016,28(1):14-16.
[4] 向珍蛹,茅建春,徐先国,等.膝骨关节炎中医证型分布的流行病学研究[J].上海中医药杂志,2012,46(12):5-8.
[5] 周明旺,梁雄勇,李盛华,等.中医体质与甘肃地区膝骨性关节炎相关性研究[J].中国中医骨伤科杂志,2013,21(5):22-24.
[6] 朱燕波,王琦,姚实林.中医阳虚质相关影响因素的研究[J].中医杂志,2007,48(12):1113-1115.
[7] 陈小野,蒋小丽,邹世洁,等.雌激素对大鼠中医体质影响的研究[J].现代中西医结合杂志,2005,14(18):2383-2385.
[8] 戴七一,谈驰,王雄,等.中老年女性膝关节骨关节炎发病与性激素水平关系的研究[J].广西中医药大学学报,2015,18(3):20-21.
[9] 戴小宇,王昭明.雌激素及其受体与骨性关节炎相关性的研究进展[J].中国矫形外科杂志,2016,24(17):1590-1593.
[10] 罗翠文.阳虚状态人群的寒性特征研究[D].广州:广州中医药大学,2015.
[11] Bautista D M,Pellegrino M,Tsunozaki M.TRPA1:A Gatekeeper for Inflammation[J].Annual Review of Physiology,2013,75(1):181-200.
[12] Mueller-Tribbensee S M,Karna M,Khalil M,et al.Differential Contribution of TRPA1,TRPV4 and TRPM8 to Colonic Nociception in Mice[J].PLoS One,2015,10(7):e128242.
[13] Nummenmaa E,H?m?l?inen M,Moilanen L J,et al.Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes[J].Arthritis Research & Therapy,2016,18(1) :185.
[14] Pereira I,Mendes S J F,Pereira D M S,et al.Transient Receptor Potential Ankyrin 1 Channel Expression on Peripheral Blood Leukocytes from Rheumatoid Arthritic Patients and Correlation with Pain and Disability[J].Frontiers in Pharmacology,2017(8):53.
[15] Phan M N,Leddy H A,Votta B J,et al.Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes[J].Arthritis & Rheumatism,2009,60(10):3028-3037.
[16] Mcnulty A L,Leddy H A,Liedtke W,et al.TRPV4 as a therapeutic target for joint diseases[J].Naunyn-Schmiedeberg′s Archives of Pharmacology,2015,388(4):437-450.
[17] Hasan R,Leeson-Payne A T S,Jaggar J H,et al.Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels[J].Scientific Reports,2017(7):45098.
[18] Aubdool A A,Graepel R,Kodji X,et al.TRPA1 is essential for the vascular response to environmental cold exposure[J].Nature Communications,2014(5):5732.
[19] Horváth á,Tékus V,Boros M,et al.Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis:in vivo study using TRPA1-deficient mice[J].Arthritis Research & Therapy,2016(18):6.
[20] Garrison S R,Stucky C L.Contribution of Transient Receptor Potential Ankyrin 1 to Chronic Pain in Aged Mice With Complete Freund′s Adjuvant-Induced Arthritis[J].Arthritis & Rheumatology,2014,66(9):2380-2390.
[21] 邢润麟,王培民,茆军,等.基于thermoTRP介导冷痛敏机制对膝骨关节炎虚寒冷痛的研究[J].南京中医药大学学报,2016,32(4):347-351.
[22] Hdud I M,El-Shafei A A,Loughna P,et al.Expression of Transient Receptor Potential Vanilloid (TRPV) Channels in Different Passages of Articular Chondrocytes[J].International Journal of Molecular Sciences,2012,13(12):4433-4445.
[23] Clark A L,Votta B J,Kumar S,et al.Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4:Age- and sex-dependent progression of osteoarthritis in Trpv4-deficient mice[J].Arthritis & Rheumatism,2010,62(10):2973-2983.
[24] Eleswarapu S V,Athanasiou K A.TRPV4 channel activation improves the tensile properties of self-assembled articular cartilage constructs[J].Acta Biomaterialia,2013,9(3):5554-5561.
[25] O′Conor C J,Ramalingam S,Zelenski N A,et al.Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis[J].Scientific Reports,2016(6):29053.
[26] Bertram K L,Banderali U,Tailor P,et al.Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells[J].Channels,2015,10(2):148-157.
[27] Guilak F,Leddy H A,Liedtke W.Transient Receptor Potential Vanilloid 4:The Sixth Sense of the Musculoskeletal System?[J].Annals of the New York Academy of Sciences,2010,1192(1):404-409.
[28] 唐宗湘.温度敏感的TRP通道与中药药性四气理论[J].南京中医药大学学报,2015,31(4):301-304.
[29] Xiao B,Dubin A E,Bursulaya B,et al.Identification of Transmembrane Domain 5 as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels[J].Journal of Neuroscience,2008,28(39):9640-9651.
[30] Hinman A,Chuang HH,Bautista DM,et al.TRP channel activation by reversible covalent modification[J].Proc Natl Acad Sci U S A,2006,103(51):19564-19568.
[31] Michael B,M S G,Wook H S,et al.Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin[J].Neuron,2004,41(6):849-857.
[32] Sven-Eric J,M B D,Huai-Hu C,et al.Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1[J].Nature,2004,427(6971):260-565.
[33] Janssens A,Gees M,Toth B I,et al.Definition of two agonist types at the mammalian cold-activated channel TRPM8[J].eLife,2016,5:e17240.
[34] 隋峰,杨娜,张畅斌,等.寒热性中药成分对TRPV1和TRPM8通道蛋白基因表达的影响[J].中国中药杂志,2010,35(12):1594-1598.
[35] 黄钊,王晖.薄荷醇影响TRP通道的研究进展[J].广东药科大学学报,2011,27(3):324-326.
[36] 张磊,李具宝,曾炎,等.膝关节骨性关节炎内服中药使用情况文献分析[J].中医杂志,2013,54(7):608-610.
[37] Wang C,Liu C,Wan H,et al.Wu-Tou Decoction Inhibits Chronic Inflammatory Pain in Mice:Participation of TRPV1 and TRPA1 Ion Channels[J].BioMed Research International,2015,2015:1-12.
[2] 王琦.9种基本中医体质类型的分类及其诊断表述依据[J].北京中医药大学学报,2005,28(4):1-8.
[3] 何栩,罗小兵,虞亚明,等.中老年女性膝骨关节炎患者中医体质类型特点的初步探讨[J].中医正骨,2016,28(1):14-16.
[4] 向珍蛹,茅建春,徐先国,等.膝骨关节炎中医证型分布的流行病学研究[J].上海中医药杂志,2012,46(12):5-8.
[5] 周明旺,梁雄勇,李盛华,等.中医体质与甘肃地区膝骨性关节炎相关性研究[J].中国中医骨伤科杂志,2013,21(5):22-24.
[6] 朱燕波,王琦,姚实林.中医阳虚质相关影响因素的研究[J].中医杂志,2007,48(12):1113-1115.
[7] 陈小野,蒋小丽,邹世洁,等.雌激素对大鼠中医体质影响的研究[J].现代中西医结合杂志,2005,14(18):2383-2385.
[8] 戴七一,谈驰,王雄,等.中老年女性膝关节骨关节炎发病与性激素水平关系的研究[J].广西中医药大学学报,2015,18(3):20-21.
[9] 戴小宇,王昭明.雌激素及其受体与骨性关节炎相关性的研究进展[J].中国矫形外科杂志,2016,24(17):1590-1593.
[10] 罗翠文.阳虚状态人群的寒性特征研究[D].广州:广州中医药大学,2015.
[11] Bautista D M,Pellegrino M,Tsunozaki M.TRPA1:A Gatekeeper for Inflammation[J].Annual Review of Physiology,2013,75(1):181-200.
[12] Mueller-Tribbensee S M,Karna M,Khalil M,et al.Differential Contribution of TRPA1,TRPV4 and TRPM8 to Colonic Nociception in Mice[J].PLoS One,2015,10(7):e128242.
[13] Nummenmaa E,H?m?l?inen M,Moilanen L J,et al.Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes[J].Arthritis Research & Therapy,2016,18(1) :185.
[14] Pereira I,Mendes S J F,Pereira D M S,et al.Transient Receptor Potential Ankyrin 1 Channel Expression on Peripheral Blood Leukocytes from Rheumatoid Arthritic Patients and Correlation with Pain and Disability[J].Frontiers in Pharmacology,2017(8):53.
[15] Phan M N,Leddy H A,Votta B J,et al.Functional characterization of TRPV4 as an osmotically sensitive ion channel in porcine articular chondrocytes[J].Arthritis & Rheumatism,2009,60(10):3028-3037.
[16] Mcnulty A L,Leddy H A,Liedtke W,et al.TRPV4 as a therapeutic target for joint diseases[J].Naunyn-Schmiedeberg′s Archives of Pharmacology,2015,388(4):437-450.
[17] Hasan R,Leeson-Payne A T S,Jaggar J H,et al.Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels[J].Scientific Reports,2017(7):45098.
[18] Aubdool A A,Graepel R,Kodji X,et al.TRPA1 is essential for the vascular response to environmental cold exposure[J].Nature Communications,2014(5):5732.
[19] Horváth á,Tékus V,Boros M,et al.Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis:in vivo study using TRPA1-deficient mice[J].Arthritis Research & Therapy,2016(18):6.
[20] Garrison S R,Stucky C L.Contribution of Transient Receptor Potential Ankyrin 1 to Chronic Pain in Aged Mice With Complete Freund′s Adjuvant-Induced Arthritis[J].Arthritis & Rheumatology,2014,66(9):2380-2390.
[21] 邢润麟,王培民,茆军,等.基于thermoTRP介导冷痛敏机制对膝骨关节炎虚寒冷痛的研究[J].南京中医药大学学报,2016,32(4):347-351.
[22] Hdud I M,El-Shafei A A,Loughna P,et al.Expression of Transient Receptor Potential Vanilloid (TRPV) Channels in Different Passages of Articular Chondrocytes[J].International Journal of Molecular Sciences,2012,13(12):4433-4445.
[23] Clark A L,Votta B J,Kumar S,et al.Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4:Age- and sex-dependent progression of osteoarthritis in Trpv4-deficient mice[J].Arthritis & Rheumatism,2010,62(10):2973-2983.
[24] Eleswarapu S V,Athanasiou K A.TRPV4 channel activation improves the tensile properties of self-assembled articular cartilage constructs[J].Acta Biomaterialia,2013,9(3):5554-5561.
[25] O′Conor C J,Ramalingam S,Zelenski N A,et al.Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis[J].Scientific Reports,2016(6):29053.
[26] Bertram K L,Banderali U,Tailor P,et al.Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells[J].Channels,2015,10(2):148-157.
[27] Guilak F,Leddy H A,Liedtke W.Transient Receptor Potential Vanilloid 4:The Sixth Sense of the Musculoskeletal System?[J].Annals of the New York Academy of Sciences,2010,1192(1):404-409.
[28] 唐宗湘.温度敏感的TRP通道与中药药性四气理论[J].南京中医药大学学报,2015,31(4):301-304.
[29] Xiao B,Dubin A E,Bursulaya B,et al.Identification of Transmembrane Domain 5 as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels[J].Journal of Neuroscience,2008,28(39):9640-9651.
[30] Hinman A,Chuang HH,Bautista DM,et al.TRP channel activation by reversible covalent modification[J].Proc Natl Acad Sci U S A,2006,103(51):19564-19568.
[31] Michael B,M S G,Wook H S,et al.Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin[J].Neuron,2004,41(6):849-857.
[32] Sven-Eric J,M B D,Huai-Hu C,et al.Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1[J].Nature,2004,427(6971):260-565.
[33] Janssens A,Gees M,Toth B I,et al.Definition of two agonist types at the mammalian cold-activated channel TRPM8[J].eLife,2016,5:e17240.
[34] 隋峰,杨娜,张畅斌,等.寒热性中药成分对TRPV1和TRPM8通道蛋白基因表达的影响[J].中国中药杂志,2010,35(12):1594-1598.
[35] 黄钊,王晖.薄荷醇影响TRP通道的研究进展[J].广东药科大学学报,2011,27(3):324-326.
[36] 张磊,李具宝,曾炎,等.膝关节骨性关节炎内服中药使用情况文献分析[J].中医杂志,2013,54(7):608-610.
[37] Wang C,Liu C,Wan H,et al.Wu-Tou Decoction Inhibits Chronic Inflammatory Pain in Mice:Participation of TRPV1 and TRPA1 Ion Channels[J].BioMed Research International,2015,2015:1-12.