

浏览全部资源
扫码关注微信
1.西南医科大学,四川 泸州 646000
2.西南医科大学 附属中医医院,四川 泸州 646000
Received:21 September 2021,
Published Online:14 December 2021,
Published:05 March 2022
移动端阅览
冉丽莎,吴亚曾,劳筱清等.糖尿病周围神经病变细胞凋亡机制及中医药干预研究进展[J].中国实验方剂学杂志,2022,28(05):256-265.
RAN Li-sha,WU Ya-zeng,LAO Xiao-qing,et al.Cell Apoptosis Mechanism and Traditional Chinese Medicine Intervention in Diabetic Peripheral Neuropathy: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):256-265.
冉丽莎,吴亚曾,劳筱清等.糖尿病周围神经病变细胞凋亡机制及中医药干预研究进展[J].中国实验方剂学杂志,2022,28(05):256-265. DOI: 10.13422/j.cnki.syfjx.20220405.
RAN Li-sha,WU Ya-zeng,LAO Xiao-qing,et al.Cell Apoptosis Mechanism and Traditional Chinese Medicine Intervention in Diabetic Peripheral Neuropathy: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(05):256-265. DOI: 10.13422/j.cnki.syfjx.20220405.
糖尿病周围神经病变是糖尿病最常见的并发症之一,其发病率高,是糖尿病患者致残、致畸、致死的主要原因。目前糖尿病周围神经病变的发病机制尚未阐述清楚,可能与氧化应激、炎症反应、微循环功能障碍、代谢异常等相关。近年研究发现,周围神经细胞凋亡在糖尿病周围神经病变的发病机制中具有重要作用。目前常见的细胞凋亡途径有线粒体通路、死亡受体通路和内质网通路,三者共同调控机体的细胞凋亡过程。中医药在糖尿病周围神经病变的治疗中疗效明确,具有整体调节、多靶点、多途径的治疗优势。研究表明,中药活性成分及复方可通过调控周围神经细胞凋亡信号通路达到改善糖尿病周围神经病变的效果。随着研究的深入,细胞凋亡途径可能成为继氧化应激后抗糖尿病周围神经病变新药研究的又一潜在靶点。因此,本文即以细胞凋亡为切入点,结合三条细胞凋亡途径相关的信号通路,综述了近年来中药干预糖尿病周围神经病变的研究进展,为糖尿病周围神经病变的临床防治及新药研发提供参考。
Diabetic peripheral neuropathy is a common complication of diabetes, and its pathogenesis is complex. Its high morbidity can result in disability, teratogenesis, and death in diabetic patients. At present, the pathogenesis of diabetic peripheral neuropathy has not been clearly elucidated, which may be related to oxidative stress, inflammatory response, microcirculation dysfunction, metabolic abnormalities, etc. Recent studies have found that apoptosis plays an important role in the pathogenesis of diabetic peripheral neuropathy. The three pathways, i.e., mitochondrial pathway, death receptor pathway, and endoplasmic reticulum pathway, jointly regulate the cell apoptosis in the body. Traditional Chinese medicine, with definite efficacies in the treatment of diabetic peripheral neuropathy, is advantageous in overall regulation and multi-target and multi-pathway treatment. As reported, the active ingredients in Chinese medicine and Chinese medicinal compounds can alleviate diabetic peripheral neuropathy by regulating apoptosis signaling pathways. Furthermore, apoptosis pathways are expected to be potential targets for new drugs against diabetic peripheral neuropathy following oxidative stress. Therefore, this paper, taking apoptosis as the entry point, reviewed the research progress on TCM intervention in diabetic peripheral neuropathy in recent years to provide references for the clinical prevention and treatment of diabetic peripheral neuropathy and the development of new drugs.
HICKS C W , SELVIN E . Epidemiology of peripheral neuropathy and lower extremity disease in diabetes [J]. Curr Diab Rep , 2019 , 19 ( 10 ): 86 .
STRYCHARZ J , RYGIELSKA Z , SWIDERSKA E , et al . SIRT1 as a therapeutic target in diabetic complications [J]. Curr Med Chem , 2018 , 25 ( 9 ): 1002 - 1035 .
LIANG W J , YANG H W , LIU H N , et al . HMGB1 upregulates NF- κ B by inhibiting IKB- α and associates with diabetic retinopathy [J]. Life Sci , 2020 , 241 : 117146 .
KE R , WANG Y , HONG S , et al . Endoplasmic reticulum stress related factor IRE1 α regulates TXNIP/NLRP3-mediated pyroptosis in diabetic nephropathy [J]. Exp Cell Res , 2020 , 396 ( 2 ): 112293 .
SADEGHIYAN GALESHKALAMI N , ABDOLLAHI M , NAJAFI R , et al . Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis [J]. Life Sci , 2019 , 216 : 101 - 110 .
王玲 , 董德勇 , 孙悦 , 等 . 糖尿病不同病程大鼠背根神经节和坐骨神经细胞凋亡的研究 [J]. 中国糖尿病杂志 , 2009 , 17 ( 2 ): 147 - 149 .
SRINIVASAN S , STEVENS M , WILEY J W . Diabetic peripheral neuropathy:evidence for apoptosis and associated mitochondrial dysfunction [J]. Diabetes , 2000 , 49 ( 11 ): 1932 - 1938 .
LIU Y P , SHAO S J , GUO H D . Schwann cells apoptosis is induced by high glucose in diabetic peripheral neuropathy [J]. Life Sci , 2020 , 248 : 117459 .
XU Y R , DONG H S , YANG W X . Regulators in the apoptotic pathway during spermatogenesis:killers or guards? [J]. Gene , 2016 , 582 ( 2 ): 97 - 111 .
杨绍杰 , 孟金萍 , 屈祎 , 等 . 细胞凋亡信号传导通路的研究进展 [J]. 中国比较医学杂志 , 2007 , 17 ( 5 ): 297 - 301 .
BOCK FJ , TAIT SWG . Mitochondria as multifaceted regulators of cell death [J]. Nat Rev Mol Cell Biol , 2020 , 21 ( 2 ): 85 - 100 .
HACKETT A R , STRICKLAND A , MILBRANDT J . Disrupting insulin signaling in Schwann cells impairs myelination and induces a sensory neuropathy [J]. Glia , 2020 , 68 ( 5 ): 963 - 978 .
ZHANG X , ZHAO S , YUAN Q , et al . TXNIP,a novel key factor to cause Schwann cell dysfunction in diabetic peripheral neuropathy,under the regulation of PI3K/Akt pathway inhibition-induced DNMT1 and DNMT3a overexpression [J]. Cell Death Dis , 2021 , 12 ( 7 ): 642 .
MADHAVI Y V , GAIKWAD N , YERRA V G , et al . Targeting AMPK in diabetes and diabetic complications:energy homeostasis,autophagy and mitochondrial health [J]. Curr Med Chem , 2019 , 26 ( 27 ): 5207 - 5229 .
ZHANG Q , LIANG X C . Effects of mitochondrial dysfunction via AMPK/PGC-1 α signal pathway on pathogenic mechanism of diabetic peripheral neuropathy and the protective effects of Chinese medicine [J]. Chin J Integr Med , 2019 , 25 ( 5 ): 386 - 394 .
吴卓超 , 宋英 , 宋必卫 . NF- κ B介导线粒体依赖的神经细胞凋亡途径 [J]. 癌变.畸变.突变 , 2014 , 26 ( 1 ): 75 - 78 .
DODINGTON D W , DESAI H R , WOO M . JAK/STAT-emerging players in metabolism [J]. Trends Endocrinol Metab , 2018 , 29 ( 1 ): 55 - 65 .
HAN J , BACK S H , HUR J , et al . ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death [J]. Nat Cell Biol , 2013 , 15 ( 5 ): 481 - 490 .
WU Y B , LI H Q , REN M S , et al . CHOP/ORP150 ratio in endoplasmic reticulum stress:a new mechanism for diabetic peripheral neuropathy [J]. Cell Physiol Biochem , 2013 , 32 ( 2 ): 367 - 379 .
ABDULLAH A , RAVANAN P . The unknown face of IRE1 α -beyond ER stress [J]. Eur J Cell Biol , 2018 , 97 ( 5 ): 359 - 368 .
SON S M , BYUN J , ROH S E , et al . Reduced IRE1 α mediates apoptotic cell death by disrupting calcium homeostasis via the InsP3 receptor [J]. Cell Death Dis , 2014 , 5 : e1188 .
张亮 , 徐敏 , 庄向华 , 等 . 内质网应激与凋亡在糖尿病周围神经病变中的表达变化 [J]. 山东大学学报:医学版 , 2017 , 55 ( 8 ): 13 - 17 .
YANG W , TIFFANY-CASTIGLIONI E , KOH H C , et al . Paraquat activates the IRE1/ASK1/JNK cascade associated with apoptosis in human neuroblastoma SH-SY5Y cells [J]. Toxicol Lett , 2009 , 191 ( 2/3 ): 203 - 210 .
吕翠岩 , 徐暾海 , 孙文 , 等 . 糖痹康对糖尿病大鼠坐骨神经c-Jun及NT-3表达的影响 [J]. 中华中医药杂志 , 2017 , 32 ( 2 ): 560 - 564 .
HO E C , LAM K S , CHEN Y S , et al . Aldose reductase-deficient mice are protected from delayed motor nerve conduction velocity,increased c-Jun NH2-terminal kinase activation,depletion of reduced glutathione,increased superoxide accumulation,and DNA damage [J]. Diabetes , 2006 , 55 ( 7 ): 1946 - 1953 .
BROWNLEE M . The pathobiology of diabetic complications:a unifying mechanism [J]. Diabetes , 2005 , 54 ( 6 ): 1615 - 1625 .
MANTUANO E , HENRY K , YAMAUCHI T , et al . The unfolded protein response is a major mechanism by which LRP1 regulates Schwann cell survival after injury [J]. J Neurosci , 2011 , 31 ( 38 ): 13376 - 13385 .
ASHKENAZI A , SALVESEN G . Regulated cell death:signaling and mechanisms [J]. Annu Rev Cell Dev Biol , 2014 , 30 : 337 - 356 .
OBROSOVA I G , LI F , ABATAN O I , et al . Role of poly(ADP-ribose) polymerase activation in diabetic neuropathy [J]. Diabetes , 2004 , 53 ( 3 ): 711 - 720 .
AL-ROUQ F . Nerve conduction study and Fas mediated apoptosis of nerve cells in peripheral neuropathy in type 2 diabetes [J]. Int J Diabetes Mellitus , 2009 , 1 : 38 - 39 .
GUILLOT R , BRINGUIER A F , POROKHOV B , et al . Increased levels of soluble Fas in serum from diabetic patients with neuropathy [J]. Diabetes Metab , 2001 , 27 ( 3 ): 315 - 321 .
ROUQ F A , HAMMAD D , MEO S A . Protection of neuronal cell death against diabetes-induced apoptosis by Fas blocker ZB4 [J]. J Int Med Res , 2014 , 42 ( 4 ): 949 - 957 .
BRENNER D , BLASER H , MAK T W . Regulation of tumour necrosis factor signalling:live or let die [J]. Nat Rev Immunol , 2015 , 15 ( 6 ): 362 - 374 .
DOSTERT C , GRUSDAT M , LETELLIER E , et al . The TNF family of ligands and receptors:communication modules in the immune system and beyond [J]. Physiol Rev , 2019 , 99 ( 1 ): 115 - 160 .
金涛 , 祝捷 . 雪旺氏细胞凋亡在TNFRⅠ -/- 鼠实验性自身免疫性神经炎发病机制中的作用 [J]. 吉林大学学报:学版 , 2007 , 33 ( 2 ): 279 - 282 .
SUN L Q , ZHAO J , ZHANG T T , et al . Protective effects of Salvianolic acid B on Schwann cells apoptosis induced by high glucose [J]. Neurochem Res , 2012 , 37 ( 5 ): 996 - 1010 .
王蒙 , 王倩倩 , 孙连庆 . 丹参酚酸B对间歇性高糖乳鼠雪旺细胞损伤的改善 [J]. 西部医学 , 2021 , 33 ( 10 ): 1418 - 1422 .
SHI Y , LIANGg X C , ZHANG H , et al . Quercetin protects rat dorsal root ganglion neurons against high glucose-induced injury in vitro through Nrf-2/HO-1 activation and NF- κ B inhibition [J]. Acta Pharmacol Sin , 2013 , 34 ( 9 ): 1140 - 1148 .
YANG X , YAO W , SHI H , et al . Paeoniflorin protects Schwann cells against high glucose induced oxidative injury by activating Nrf2/ARE pathway and inhibiting apoptosis [J]. J Ethnopharmacol , 2016 , 185 : 361 - 369 .
WANG B B , WANG J L , YUAN J , et al . Sugar composition analysis of Fuzi polysaccharides by HPLC-MSn and their protective effects on schwann cells exposed to high glucose [J]. Molecules , 2016 , 21 ( 11 ): 1496 .
FAN L , ZHANG H , LI X , et al . Emodin protects hyperglycemia-induced injury in PC-12 cells by up-regulation of miR-9 [J]. Mol Cell Endocrinol , 2018 , 474 : 194 - 200 .
BEN Y , HAO J , ZHANG Z , et al . Astragaloside Ⅳ inhibits mitochondrial-dependent apoptosis of the dorsal root ganglion in diabetic peripheral neuropathy rats through modulation of the SIRT1/p53 signaling pathway [J]. Diabetes Metab Syndr Obes , 2021 , 14 : 1647 - 1661 .
孙青 , 梁晓春 , 张宏 , 等 . 筋脉通含药血清对高糖培养背根神经节神经元氧化应激及细胞凋亡的影响 [J]. 中成药 , 2013 , 35 ( 7 ): 1390 - 1395,1448 .
YIN DH , LIANG XC , ZHAO LI , et al . Jinmaitong decreases sciatic nerve DNA oxidative damage and apoptosis in a streptozotocin-induced diabetic rat model [J]. Exp Ther Med , 2015 , 10 ( 2 ): 778 - 786 .
梁俊清 , 徐海波 , 陈檬 , 等 . 周络通提取物Z-6对高糖所致Schwann细胞损伤和PI3K/Akt/nNOS通路的影响 [J]. 中国病理生理杂志 , 2014 , 30 ( 10 ): 1778 - 1783 .
易文明 , 孙文 , 郭翔宇 , 等 . 糖痹康对糖尿病周围神经病变大鼠氧化应激及细胞凋亡的影响 [J]. 环球中医药 , 2015 , 8 ( 7 ): 798 - 802 .
易文明 , 孙文 , 郭翔宇 , 等 . 糖痹康对STZ诱导的DPN大鼠坐骨神经细胞凋亡Drp1信号通路的影响 [J]. 陕西中医 , 2015 , 36 ( 6 ): 757 - 759 .
翁思颖 , 柴可夫 . 运脾和络汤对糖尿病大鼠坐骨神经Drp-1介导细胞凋亡线粒体途径的影响 [J]. 中华中医药杂志 , 2018 , 33 ( 6 ): 2336 - 2339 .
贲莹 , 张天雅 , 田佳鑫 , 等 . 基于SIRT1/p53介导的细胞凋亡途径探讨补阳还五汤对糖尿病周围神经病变的治疗作用及方中黄芪用量 [J]. 中国实验方剂学杂志 , 2022 , 28 ( 2 ): 9 - 18 .
WANG Q Q , ZHAI C , ZHU Y T , et al . Salvianolic acid B inhibits the development of diabetic peripheral neuropathy by suppressing autophagy and apoptosis [J]. J Pharm Pharmacol , 2019 , 71 ( 3 ): 417 - 428 .
KONG D , GUO Z , YANG W , et al . Tanshinone Ⅱ A affects diabetic peripheral neuropathic pain via spinal dorsal horn neuronal circuitry by modulating endoplasmic reticulum stress pathways [J]. Exp Clin Endocr Diab , 2019 , 128 ( 1 ): 59 - 65 .
ZHU Y , HAN S , LI X , et al . Paeoniflorin effect of schwann cell-derived exosomes ameliorates dorsal root ganglion neurons apoptosis through IRE1 α pathway [J]. Evid Based Complement Alternat Med , 2021 , doi: 10.1155/2021/6079305 http://dx.doi.org/10.1155/2021/6079305 .
史浩田 , 姚伟洁 , 杨鑫伟 , 等 . 糖络宁对糖尿病周围神经病变大鼠PERK-CHOP-Caspase-12通路的影响 [J]. 环球中医药 , 2017 , 10 ( 3 ): 269 - 274 .
YAO W , YANG X , ZHU J , et al . Tang-luo-ning,a traditional Chinese medicine,inhibits endoplasmic reticulum stress-induced apoptosis of schwann cells under high glucose environment [J]. Evid Based Complement Alternat Med:Ecam , 2017 , 2017 : 5193548 . DOI: 10.1155/2017/5193548 http://dx.doi.org/10.1155/2017/5193548 .
李潇 , 王婷婷 , 杨鑫伟 , 等 . 糖络宁对糖尿病周围神经病变中IRE1-TRAF2-XBP-1途径的影响 [J]. 医学研究杂志 , 2018 , 47 ( 11 ): 33 - 40 .
李潇 , 姚伟洁 , 杨鑫伟 , 等 . 糖络宁对糖尿病周围神经病变大鼠坐骨神经功能及内质网应激IRE1 α -XBP-1-CHOP通路的影响 [J]. 湖南中医药大学学报 , 2019 , 39 ( 7 ): 841 - 847 .
陈枫 , 郭宇鑫 , 王利莹 , 等 . 糖络宁对糖尿病周围神经病变大鼠细胞凋亡相关通路的影响 [J]. 中国医药导报 , 2020 , 17 ( 29 ): 4 .
YANG X , YAO W , LIU H , et al . Tangluoning,a traditional Chinese medicine,attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway [J]. Sci Rep , 2017 , 7 ( 1 ): 1014 .
刘蒙蒙 . 芪归糖痛宁颗粒对2型糖尿病周围神经病变患者临床疗效观察及对模型大鼠PERK、CHOP表达影响 [D]. 合肥 : 安徽中医药大学 , 2020 .
魏刚 , 王宏涛 , 张会欣 , 等 . 周络通胶囊对糖尿病周围神经病变模型小鼠坐骨神经细胞凋亡的保护作用研究 [J]. 中国药房 , 2013 , 24 ( 35 ): 3265 - 3268 .
ZHAO N , LI J , LI L , et al . Molecular network-based analysis of guizhi-shaoyao-zhimu decoction,a TCM herbal formula,for treatment of diabetic peripheral neuropathy [J]. Acta Pharmacol Sin , 2015 , 36 ( 6 ): 716 - 723 .
尤良震 , 吴袁元 , 尹昀东 , 等 . 丹蛭降糖胶囊对高糖诱导的人脐静脉内皮细胞凋亡及线粒体途径与死亡受体途径的影响 [J]. 中华中医药杂志 , 2019 , 34 ( 8 ): 3675 - 3680 .
常庚 , 孙大勇 , 常风云 , 等 . 益气通络法对糖尿病周围神经病变大鼠坐骨神经细胞凋亡和HO-1表达的影响 [J]. 天津中医药大学学报 , 2014 , 33 ( 4 ): 216 - 218 .
郭仪 . 益糖康调控DPN模型大鼠BDNF/TrkB系统抗DRG细胞凋亡的实验研究 [D]. 沈阳 : 辽宁中医药大学 , 2017 .
李丹 , 谭云霞 , 喻保军 , 等 . 过氧化氢酶 [J]. 营养学报 , 2020 , 42 ( 3 ): 281 - 286 .
0
Views
22
下载量
3
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621