Volume 42 Issue 2
Mar.  2021
Turn off MathJax
Article Contents
Xin GUO, Wei LAI, Yan-hua LI, Yun-ru CHEN, Ao-ran YE, Shun-song TANG, Jing LUO. Role of Phospholipase C epsilon 1 in Neuropathic Pain of Rats with Type 1 Diabetes[J]. Journal of Kunming Medical University, 2021, 42(2): 23-28. doi: 10.12259/j.issn.2095-610X.S20210206
Citation: Xin GUO, Wei LAI, Yan-hua LI, Yun-ru CHEN, Ao-ran YE, Shun-song TANG, Jing LUO. Role of Phospholipase C epsilon 1 in Neuropathic Pain of Rats with Type 1 Diabetes[J]. Journal of Kunming Medical University, 2021, 42(2): 23-28. doi: 10.12259/j.issn.2095-610X.S20210206

Role of Phospholipase C epsilon 1 in Neuropathic Pain of Rats with Type 1 Diabetes

doi: 10.12259/j.issn.2095-610X.S20210206
  • Received Date: 2020-11-14
  • Publish Date: 2021-03-05
  •   Objective  To elucidate the pathogenic role of phospholipase C epsilon 1 (PLCE1) in neuropathic pain of rats with type 1 diabetes by observing the effect of intrathecal injection of exoenzyme C3 (a RhoA inhibitor) on the activity of PLCE1 and inflammatory response in the spinal cord.  Methods  Twenty-four 8-week-old healthy male Sprague-Dawley (SD) rats were randomly allocated to healthy rats plus vehicle group (Group C), healthy rats plus exoenzyme C3 group (Group E), type 1 diabetic neuropathic pain rats induced by streptozotocin (STZ) plus vehicle group (Group DNP) and type 1 diabetic neuropathic pain rats plus exoenzyme C3 group (Group EG). The diabetic neuropathic pain model of STZ -induced type 1 diabetes in rats was established by a single intravenous injection of STZ (65 mg/kg). In Group E and Group EG, 10 µL exoenzyme C3 (1 pg/µL ) was injected intrathecally once a day for 7 consecutive days, whereas vehicle was injected intrathecally in Group C and Group DNP. Accu-Chek Compact Plus glucose meter was used to measure fasting blood glucose concentration (mmol/L) in the tail vein once weekly. Western blot was used to detect the expressions of total RhoA and PLCE1 in the spinal cord in rats, while the RhoA activity detection kit was used to measure the expression of RhoA-GTP protein. The expression of PLCE1 protein and the ratio of RhoA-GTP/ total RhoA were used to estimate the activities of PLCE1 and RhoA, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the contents of TNF-α and IL-6 in spinal cord to evaluate proinfammatory cytokines- induced the inflammation. The severity of DNP was evaluated by thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT).  Results  No significant difference was detected between group C and group E. Rats with DNP had a decreased pain threshold (P < 0.05), up-regulated activities of RhoA and PLCE1 (P < 0.05) and increased production of TNF-α and IL-6 in spinal cord (P < 0.05) as compared to the group C and group E. Intrathecal injection of exoenzyme C3 rather than vehicle decreased the activity of RhoA in spinal cord (P < 0.05) of type 1 DNP rats, accompanied by a down-regulation of PLCE1 activity and proinflammatory mediators (P < 0.05) and a relief of DNP (P < 0.05).  Conclusion  PLCE1 plays an important role in type 1 diabetic neuropathic pain by promoting spinal cord inflammation, and its activity is regulated by RhoA.
  • loading
  • [1]
    Fitri A,Sjahrir H,Bachtiar A,et al. Modulation of interleukin-8 production by vitamin D supplementation in indonesian patients with diabetic polyneuropathy:A randomized clinical trial[J]. Oman Med J,2020,35(5):e168. doi: 10.5001/omj.2020.110
    [2]
    Kanoko Umezawa,Tatsuya Nagano,Kazuyuki Kobayashi,et al. Phospholipase cε plays a crucial role in neutrophilic inflammation accompanying acute lung injury through augmentation of cxc chemokine production from alveolar epithelial cells[J]. Respir Res,2019,20(1):9. doi: 10.1186/s12931-019-0975-4
    [3]
    Stephanie S Dusaban,Nicole H Purcell,Edward Rockenstein,et al. Phospholipase c epsilon links g protein-coupled receptor activation to inflammatory astrocytic responses[J]. Proc Natl Acad Sci U S A,2013,110(9):3609-3614. doi: 10.1073/pnas.1217355110
    [4]
    Alan V Smrcka,Joan Heller Brown,George G Holz. Role of phospholipase cε in physiological phosphoinositide signaling networks[J]. Cell Signal,2012,24(6):1333-1343. doi: 10.1016/j.cellsig.2012.01.009
    [5]
    Wang C,Song S,Zhang Y,et al. Inhibition of the rho/rho kinase pathway prevents lipopolysaccharide-induced hyperalgesia and the release of TNF-α and IL-1β in the mouse spinal cord[J]. Sci Rep,2015,5:14553. doi: 10.1038/srep14553
    [6]
    Dan Zhu,Tingting Fan,Xinyue Huo,et al. Progressive increase of inflammatory cxcr4 and tnf-alpha in the dorsal root ganglia and spinal cord maintains peripheral and central sensitization to diabetic neuropathic pain in rats[J]. Mediators Inflamm,2019,19:4856156.
    [7]
    Dang J K,Wu Y,Cao H,et al. Establishment of a rat model of type II diabetic neuropathic pain[J]. Pain Med,2014,15(4):637-46.
    [8]
    Masahiro Ohsawa,Megumi Aasato,Shun-Suke Hayashi,et al. Rhoa/rho kinase pathway contributes to the pathogenesis of thermal hyperalgesia in diabetic mice[J]. Pain,2011,152(1):114-122. doi: 10.1016/j.pain.2010.10.005
    [9]
    袁凌跃,李江,杨泳,等. 白三烯B4在“肺保护性”通气致肺损伤中的作用机制[J]. 南方医科大学学报,2020,40(10):1465-1471.
    [10]
    Stino A M,Smith A G. Peripheral neuropathy in prediabetes and the metabolic syndrome[J]. J Diabetes Investig,2017,8(5):646-655. doi: 10.1111/jdi.12650
    [11]
    Gareth S D Purvis,Massimo Collino,Rodrigo A Loiola,et al. Identification of annexina1 as an endogenous regulator of rhoa,and its role in the pathophysiology and experimental therapy of type-2 diabetes[J]. Front Immunol,2019,10:571. doi: 10.3389/fimmu.2019.00571
    [12]
    Xie Y,Song T,Huo M,et al. Fasudil alleviates hepatic fibrosis in type 1 diabetic rats:involvement of the inflammation and rhoa/rock pathway[J]. Eur Rev Med Pharmacol Sci,2018,22(17):5665-5677.
    [13]
    Gao F,Zheng Z M. Animal models of diabetic neuropathic pain[J]. Exp Clin Endocrinol Diabetes,2014,122(2):100-106. doi: 10.1055/s-0033-1363234
    [14]
    Jun-Min Zhong,Yue-Cheng Lu,Jing Zhang. Dexmedetomidine reduces diabetic neuropathy pain in rats through the wnt 10a/β-catenin signaling pathway[J]. Biomed Res Int,2018,18:9043628.
    [15]
    Ji-Yuan Zhao,Li Yang,Hu-Hu Bai,et al. Inhibition of protein tyrosine phosphatase 1b in spinal cord dorsal horn of rats attenuated diabetic neuropathic pain[J]. Eur J Pharmacol,2018,827:189-197. doi: 10.1016/j.ejphar.2018.03.012
    [16]
    Lu Y,Lin B,Zhong J. The therapeutic effect of dexmedetomidine on rat diabetic neuropathy pain and the mechanism[J]. Biol Pharm Bull,2017,40(9):1432-1438. doi: 10.1248/bpb.b17-00224
    [17]
    Dolores Piniella,Elena Martínez-Blanco,Ignacio Ibáñez,et al. Identification of novel regulatory partners of the glutamate transporter GLT-1[J]. Glia,2018,66(12):2737-2755. doi: 10.1002/glia.23524
    [18]
    Pyne S,Adams D R,Pyne N J. Sphingosine 1-phosphate and sphingosine kinases in health and disease:Recent advances[J]. Prog Lipid Res,2016,62:93-106. doi: 10.1016/j.plipres.2016.03.001
  • Relative Articles

    [1] Jingyu YAO, Rui WEI, Lin ZHANG, Shengliu SHI, Peng BAI. The Effects of NLR,PLR,and FRA in Peripheral Blood on Normal Bone Mass and Bone Loss after Fractures. Journal of Kunming Medical University, 2024, 45(11): 123-127.  doi: 10.12259/j.issn.2095-610X.S20241117
    [2] Jinrun YANG, Huanhuan ZHAO, Zhicong WU, Gerui YU, Lan MA, Yufen CHEN, Manyi XIE, Yu DONG. Huashi Runjing Decoction Amelioretes the Inflammatory Response of Castrated Male Dry Eye Disease Rats by Regulating COX-2,TNF-α,and IL-6 Proteins. Journal of Kunming Medical University, 2023, 44(11): 38-46.  doi: 10.12259/j.issn.2095-610X.S20231106
    [3] Guili LIANG, Canmei LI, Chengfeng XING, Yunlong DONG, Juan WANG, Zi LEI, Yinglei MIAO, Danfeng LAN. Changes of Intestinal Inflammatory Injury Induced by DSS in GC-C-/- Mice. Journal of Kunming Medical University, 2022, 43(7): 1-8.  doi: 10.12259/j.issn.2095-610X.S20220712
    [4] Yan JIANG, Zhengke ZHAO, Guangyan WANG, Liangang XU, Mengdie LI, Maofan WANG, Shuangmei LONG, Jiao LIU, Jin QIAN. Diagnostic Value of Combined Detection of Serum GAD,ICA and C-P in Type I Diabetes Mellitus. Journal of Kunming Medical University, 2022, 43(4): 99-102.  doi: 10.12259/j.issn.2095-610X.S20220416
    [5] Xue LOU, Li LIAO, Ruo-tong ZHAO, Xiang-yu WANG, Yi-fan YANG, Shuang LIU, Jian XU. Clinical Significance of Anti-dsDNA Antibody,Complement C3 and Other Laboratory Indicators in the Diagnosis of Renal Injury in Systemic Lupus Erythematosus. Journal of Kunming Medical University, 2021, 42(2): 49-53.  doi: 10.12259/j.issn.2095-610X.S20210214
    [6] Jian XU, Le LI, Yan-li HUANG, Jin-shu GUI, Ya-hong LI, Lei MA. Expression of Inflammatory Cytokines TNF-α and IL-6 in Patients with Chronic Thromboembolic Pulmonary Hypertension and Their Clinical Significance. Journal of Kunming Medical University, 2021, 42(6): 119-123.  doi: 10.12259/j.issn.2095-610X.S20210631
    [7] Li Meng Nan , Xu Huan Huan , Liu Ya Nan , Yang Shuang , Li Chong Yang , Xu Shi Lian . . Journal of Kunming Medical University, 2020, 41(05): 7-12.
    [8] Liu YANG, Qi-cai QU, Rui CHEN, Shu-lan JIAO, Yong-yu SI, Hua ZHOU. Effects of Dexmedetomidine on Inflammatory Response in Rats with Smoke Inhalation Lung Injury. Journal of Kunming Medical University, 2020, 41(11): 30-37.  doi: 10.12259/j.issn.2095-610X.S20201124
    [9] Bin HUANG, Rui-hua ZHAO, Qi-hua FEI, Jian-wei LI, Yan ZHI, Wen-jun LIU, Xiao-qing LI. Effect of Ulinastatin Combined with Continuous Renal Replacement Therapy in Treatment of Severe Burn Patients and Its Influence on Inflammatory Factors and 28-day all-cause Mortality. Journal of Kunming Medical University, 2020, 41(11): 109-113.  doi: 10.12259/j.issn.2095-610X.S20201102
    [10] Dong Wei , Yuan Xiao Lin , Li Jiao , Li Zheng Yan , Liu Wei Tong , Yu Xiao Ling , Zhang Ying . The Research of Effects of Applying Cataplasm of Paris Polyphylla Smith Var. Yunnanensis (Franch.) Hand.-Mazz on Acute Gouty Arthritis and Inflammation. Journal of Kunming Medical University, 2018, 39(02): 21-24.
    [11] Qiu Gao Gao , Zhang Ji Ping , Yin Hui Lin , Li Zuo Hong , Zhang Wei Qiang . . Journal of Kunming Medical University, 2018, 39(10): 58-62.
    [12] Du Hai Yan . 鼠神经生长因子联合红花黄素治疗老年糖尿病合并脑梗. Journal of Kunming Medical University,
    [13] Hong Xu Hua . Effects of Tuberculosis Drugs Combined with Rifapentine on the Immune Function, Inflammatory Factors, VEGF and MMP-9 of TB Patients. Journal of Kunming Medical University,
    [14] Teng Yan . Effect of Hemoperfusion on Inflammation Factors in Patients with Sepsis. Journal of Kunming Medical University,
    [15] Li Jun Jie . The Gene Expression Change of Inflammatory Factors TNF-α, IL-6 and IL-1βin Cerebral Ischemia-Reperfusion Rats. Journal of Kunming Medical University,
    [16] Wang Xiang Yun . . Journal of Kunming Medical University,
    [17] Kui Li Yue . . Journal of Kunming Medical University,
    [18] He Yan . . Journal of Kunming Medical University,
    [19] He Ying Hong . . Journal of Kunming Medical University,
    [20] . . Journal of Kunming Medical University,
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(2)  / Tables(3)

    Article Metrics

    Article views (2626) PDF downloads(132) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return