青钱柳叶对2型糖尿病大鼠骨骼肌炎症反应、胰岛素通路蛋白及糖原合成的影响
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  • 英文篇名:Influence of Qingqianliuye(leaf of Cyclocarya paliurus ) on skeletal muscle inflammatory response,insulin pathway proteins and glycogen synthesis in T2DM rats
  • 作者:姚骏凯 ; 高学敏 ; 张建军 ; 李伟 ; 付璐 ; 王蕾蕾 ; 贾岚 ; 赵秀婷 ; 王景霞
  • 英文作者:Yao Junkai;Gao Xuemin;Zhang Jianjun;Li Wei;Fu Lu;Wang Leilei;Jia Lan;Zhao Xiuting;Wang Jingxia;Beijing University of Chinese Medicine;Infinitus(China) Company LTD.;
  • 关键词:青钱柳叶 ; 2型糖尿病 ; 骨骼肌炎症反应 ; 胰岛素通路蛋白 ; 糖原合成 ; 大鼠
  • 英文关键词:Qingqianliuye(leaf of Cyclocarya paliurus);;type 2 diabetes mellitus;;skeletal muscle inflammatory response;;insulin pathway proteins;;glycogen synthesis;;rats
  • 中文刊名:JZYB
  • 英文刊名:Journal of Beijing University of Traditional Chinese Medicine
  • 机构:北京中医药大学;无限极中国有限公司;
  • 出版日期:2018-11-30
  • 出版单位:北京中医药大学学报
  • 年:2018
  • 期:v.41
  • 基金:国家自然科学基金资助项目(No.81673617)~~
  • 语种:中文;
  • 页:JZYB201811008
  • 页数:7
  • CN:11
  • ISSN:11-3574/R
  • 分类号:50-56
摘要
目的研究青钱柳叶水提物对2型糖尿病(T2DM)大鼠骨骼肌炎症反应、胰岛素通路蛋白及糖原合成的影响。方法高脂饲料喂养8周加单次腹腔注射小剂量链脲佐菌素(30 mg/kg)建立T2DM大鼠模型,将成模大鼠随机分为模型组,二甲双胍组,青钱柳叶水提物低、中、高剂量组,每组10只;正常组和模型组给予0. 9%氯化钠溶液,二甲双胍组给予二甲双胍混悬液(0. 3 g/kg),青钱柳叶水提物低、中、高剂量组分别给予青钱柳叶水提物(0. 25、0. 5、1 g/kg),连续给药4周。处死大鼠,骨骼肌匀浆比色法检测游离脂肪酸(FFA)、糖原;放射性免疫法检测肿瘤坏死因子α(TNF-α)、白介素6(IL-6),白介素1β(IL-1β);酶联免疫吸附法检测IκB激酶(IKK)、核转录因子κB(NF-κB)、c-Jun氨基端激酶1(JNK1)、胰岛素受体底物1(IRS1)、磷酸化胰岛素受体底物1(P-IRS1)、磷脂酰肌醇3激酶(PI3K)、葡萄糖转运蛋白4(GLUT4)、糖原合成酶(GS)含量。结果与模型组比较,青钱柳叶水提物低、中、高剂量组FFA、TNF-α、IL-6、IL-1β显著降低(P <0. 05,P <0. 01);炎症通路蛋白IKK、NF-κB、JNK1含量显著降低(P <0. 05,P <0. 01); IRS1、P-IRS1、PI3K、GLUT4、GS的蛋白表达量和糖原含量显著提高(P <0. 05,P <0. 01)。结论青钱柳叶水提物提高T2DM大鼠骨骼肌中胰岛素通路及糖原合成蛋白的含量,增加肌糖原的合成,其机制可能与青钱柳叶水提物可降低骨骼肌中促炎症因子的含量、抑制炎症通路蛋白的表达、缓解代谢性炎症反应有关。
        Objective To study the influence of Qingqianliuye( leaf of Cyclocarya paliurus) aqueous extract( CPAE) on skeletal muscle inflammatory response,insulin pathway proteins and glycogen synthesis in rats with type 2 diabetes mellitus( T2 DM). Methods T2 DM rat model was established by high-fat diet for 8 weeks and intraperitoneal injection of low-dose STZ( 30 mg/kg). The control rats were included into normal group,and modeled rats were divided into model group,metformin group,lowdose,mid-dose and high-dose CPAE groups. The normal group and model group were given 0. 9% NaCI solution,metformin group was given metformin suspension( 0. 3 g/kg),and CPAE groups were given,respectively,CPAE( 0. 25 g/kg,0. 5 g/kg and 1 g/kg) for 4 weeks. After executed rats,the levels of free fatty acid( FFA) and glycogen in skeletal muscle homogenate were detected by using chromatoptometry. The levels of tumor necrosis factor-α( TNF-α), interleukin-6( IL-6) and interleukin-1β( IL-1β) were detected by using radioimmunoassay( RIA). The content of IκB kinase( IKK),nuclear factor-κB( NF-κB),c-Jun N-terminal kinase 1( c-JNK1),insulin receptor substrate 1( IRS1),phosphorylated insulin receptor substrate 1( P-IRS1),phosphatidylinositol 3-kinase( PI3 K),glucose transporter 4( GLUT4) and glycogen synthase( GS) were detected by using ELISA. Results Compared with model group,the levels of FFA,TNF-α,IL-6 and IL-1β decreased significantly in all CPAE groups( P < 0. 05,P < 0. 01). The content of IKK,NF-κB and JNK1 proteins of inflammatory pathway decreased significantly in all CPAE groups( P < 0. 05,P < 0. 01). The protein expressions of IRS1,P-IRS1,PI3 K,GLUT4 and GS,and glycogen content increased significantly in all CPAE groups( P < 0. 05,P < 0. 01). Conclusion CPAE raises the content of skeletal muscle insulin pathway proteins and glycogen synthesis protein,inhibits expressions of inflammatory pathway proteins,and improves glycogen synthesis in T2 DM rats. The mechanism may be related to that CPAE can reduce content of skeletal muscle pro-inflammatory factors,inhibit expressions of inflammatory pathway proteins,and relieve metabolic inflammatory response.
引文
[1]Asghar A,Sheikh N. Role of immune cells in obesity induced low grade inflammation and insulin resistance[J].Cell Immunol,2017,315(5):18-26.
    [2]Lackey DE,Olefsky JM. Regulation of metabolism by the innate immune system[J]. Nat Rev Endocrinol,2016,12(1):15-28.
    [3]Haghani K,Pashaei S,Vakili S,et al. TNF-αknockdown alleviates palmitate-induced insulin resistance in C2C12skeletal muscle cells[J]. Biochemical and Biophysical Research Communications,2015,460(4):977-982.
    [4] Lee H,Lim Y. Tocotrienol-rich fraction supplementation reduces hyperglycemia-induced skeletal muscle damage through regulation of insulin signaling and oxidative stress in type 2 diabetic mice[J]. J Nutr Biochem,2018,57(6):77-85.
    [5]Sadeghi A,Seyyed ES,Golestani A,et al. Resveratrol ameliorates palmitate-induced inflammation in skeletal muscle cells by attenuating oxidative stress and JNK/NF-kappa B pathway in a SIRT1-independent mechanism[J]. J Cell Biochem,2017,118(9):2654-2663.
    [6]Tam CS,Sparks LM,Johannsen DL,et al. Low macrophage accumulation in skeletal muscle of obese type 2 diabetics and elderly subjects[J]. Obesity(Silver Spring),2012,20(7):1530-1533.
    [7]Ciaraldi TP,Ryan AJ,Mudaliar SR,et al. Altered myokine secretion is an intrinsic property of skeletal muscle in type 2 diabetes[J]. PLo S One,2016,11(7):189-209.
    [8]姚骏凯,高学敏,付璐,等.青钱柳叶对2型糖尿病大鼠糖脂代谢影响[J].中华中医药杂志,2018,33(7):3138-3142.Yao JK,Gao XM,Fu L,et al. Effects of Cyclocarya paliurus on glucose and lipid metabolism in T2D rats[J]. China Journal of Traditional Chinese Medicine&Pharmacy,2018,33(7):3138-3142.
    [9] Patsouris D,Cao JJ,Vial G,et al. Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans[J]. PLo S One,2014,9(10):1106-1133.
    [10] Wu HZ,Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity[J]. J Clin Invest,2017,127(1):43-54.
    [11]Agrawal N,Delanoue R,Mauri A,et al. The drosophila TNF eiger is an adipokine that acts on insulin-producing cells to mediate nutrient response[J]. Cell Metab,2016,23(4):675-684.
    [12]范冠杰,孙晓泽,唐咸玉,等.降糖补肾方对糖尿病大鼠IKKβmRNA表达的影响[J].北京中医药大学学报,2011,34(6):402-404.Fan GJ,Sun XZ,Tang XY,et al. Influence of Jiang Tang Bu Shen Fang on expression of IKKβmRNA in diabetic rats[J]. Journal of Beijing University of Traditional Chinese Medicine,2011,34(6):402-404.
    [13]Boon J,Hoy AJ,Stark R,et al. Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance[J]. Diabetes,2013,62(2):401-410.
    [14] Mcnelis JC,Olefsky JM. Macrophages,immunity,and metabolic disease[J]. Immunity,2014,41(1):36-48.
    [15] Saltiel AR,Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism[J]. Nature,2001,414(6865):799-806.
    [16]Voss TS,Vendelbo MH,Kampmann U,et al. Acute hypoglycemia in healthy humans impairs insulin-stimulated glucose uptake and glycogen synthase in skeletal muscle:a randomized clinical study[J]. Diabetes,2017,66(9):2483-2494.
    [17]高飞,王景霞,刘静,等.青钱柳叶与葛根水提物对糖尿病大鼠模型的降血糖作用及其机制研究[J].世界中西医结合杂志,2017,12(4):507-512.Gao F,Wang JX,Liu J,et al. Anti-Glucose Effects of Cyclocarya Paliurus and Pueraria Lobata extract and their mechanism in the diabetes rat model[J]. World Journal of Integrated Traditional&Western Medicine,2017,12(4):507-512.
    [18]Dali-Youcef N,Mecili M,Ricci R,et al. Metabolic inflammation:connecting obesity and insulin resistance[J].Ann Med,2013,45(3):242-253.
    [19]姚骏凯,王景霞,高学敏,等.青钱柳叶水提物对2型糖尿病大鼠胰腺细胞凋亡的影响[J].北京中医药大学学报,2018,41(8):663-669Yao JK,Wang JX,Gao XM,et al. Effects of Cyclocarya Paliurus extract on pancreaticβcell apoptosis in type 2diabetic(T2D)rats[J]. Journal of Beijing University of Traditional Chinese Medicine,2018,41(8):663-669
    [20]黄学民,赵进喜,张亚欣.论糖尿病肾病疏风通络治法及其抗炎抗免疫损伤作用[J].北京中医药大学学报(中医临床版),2012,19(1):44-46.Huang XM,Zhao JX,Zhang YX. Therapy of dispersing wind and freeing collateral vessels for diabetic nephropathy and its effects of anti-inflammation and anti-immune injury[J]. Journal of Beijing University of Traditional Chinese Medicine(Clinical Medicine),2012,19(1):44-46.

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