五味子多糖对2型糖尿病大鼠血清中炎症因子的影响及其作用机制

doi:10.13481/j.1671-587x.20200109

摘要/Abstract

摘要： 目的：观察五味子多糖（SCP）对高脂饮食联合小剂量链脲佐菌素（STZ）诱导的2型糖尿病（T2DM）模型大鼠血清中炎症因子的影响，并探讨其治疗T2DM的可能机制。方法：雄性Wistar大鼠给予高脂饮食喂养，并一次性腹腔注射小剂量STZ（30 mg·kg^-1）建立T2DM模型。将造模成功的大鼠随机分为模型组、低剂量（25 mg·kg^-1）SCP组、中剂量（50 mg·kg^-1）SCP组和高剂量（100 mg·kg^-1）SCP组，每组10只，另取10只健康大鼠设为正常对照组。灌胃治疗8周后，各组大鼠行口服葡萄糖耐量试验（OGTT），采用葡萄糖氧化酶法检测空腹血糖（FBG），放射免疫分析法检测空腹血胰岛素（INS）水平并计算胰岛素敏感指数（ISI），采用酶联免疫吸附法（ELISA）检测大鼠血清中白细胞介素6（IL-6）、C反应蛋白（CRP）、白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）和核因子-κB（NF-κB）水平，HE染色观察大鼠胰腺组织病理形态表现。结果：与正常对照组比较，模型组大鼠FBG明显升高（P<0.01），血糖曲线下面积（AUC）明显增加，INS水平和ISI明显降低（P<0.05或P<0.01），血清中IL-6、CRP、IL-1β、TNF-α和NF-κB水平均明显升高（P<0.05或P<0.01）。与模型组比较，不同剂量SCP组大鼠FBG水平明显降低（P<0.05），血糖AUC明显下降，INS水平和ISI明显升高（P<0.05），血清中IL-6、CRP、IL-1β、TNF-α和NF-κB水平均明显降低（P<0.05或P<0.01）。与低剂量SCP组比较，中和高剂量SCP组大鼠FBG水平明显降低（P<0.05），高剂量SCP组大鼠血清中INS水平明显升高（P<0.05）。HE染色，与正常对照组比较，模型组大鼠胰岛萎缩，胰岛内细胞数目减少，边界不整；与模型组比较，不同剂量SCP组大鼠胰岛边界逐渐清晰，面积增大，细胞数目明显增加。结论：SCP可降低高脂饮食联合小剂量STZ诱导的T2DM大鼠FBG水平，升高INS水平，改善胰岛素抵抗（IR），其作用机制可能与抑制机体的炎症反应有关。

关键词: 五味子多糖, 2型糖尿病, 炎症因子, 高脂饮食, 链脲佐菌素, 空腹血糖

Abstract: Objective: To observe the effect of Schisandra Chinensis polysaccharide (SCP) on the serum inflammatory factors in the rats with type 2 diabetes mellitus (T2DM) induced by high-fat diet and lowdose of streptozotocin (STZ), and to explore its underlying mechanism in the treatment of T2DM. Methods: The male Wistar rats were given high-fat diet and introperieoneally injected with low dose of STZ (30 mg·kg^-1) in one time to establish the rat T2DM models. The successful model rats were randomly divided into model group, low dose (25 mg·kg^-1) of SCP group, middle dose (50 mg·kg^-1) of SCP group and high dose (100 mg·kg^-1) of SCP group; there were 10 rats in each group. Another 10 healthy rats were used as normal control group. Eight weeks after the intragastric administration of SCP, oral glucose tolerance test (OGTT) was performed in the rats of various groups. The fasting blood glucose (FBG) and insulin (INS) levels were detected by glucose oxidase method and radioimmunoassay method, respectively, and the insulin sensitivity index (ISI) was calculated. The levels of interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in serum of the rats were measured by enzyme linked immunosorbent assay (ELISA) method. HE staining was used to observe the pathomorphology of pancreas tissue of the rats. Results: Compared with normal control group, the serum FBG level of the rats in model group was significantly increased (P<0.01), and the area under the curve(AUC) of blood glucose of the rats was significantly increased, the serum INS level and the ISI were significantly decreased (P<0.05 or P<0.01); the levels of IL-6, CRP, IL-1β, TNF-α, and NF-κB in serum were all significantly increased (P<0.05 or P<0.01). Compared with model group, the serum FBG levels of the rats in different doses of SCP groups were markedly decreased (P<0.05), the AUC of blood glucose of the rats were significantly decreased, the INS and the ISI levels were significantly elevated (P<0.05); the levels of IL-6, CRP, IL-1β, TNF-α and NF-κB in serum were significantly decreased (P<0.05 or P<0.01). Compared with low dose of SCP group, the FBG levels of the rats in middle and high doses of SCP groups were significantly decreased(P<0.05),the serum INS level of the rats in high dose of SCP group was significantly increased(P<0.05). The HE staining results showed that compared with normal control group, the islets were atrophied, the number of cells in islets was decreased and the boundary was irregular in model group; compared with model group,the islet boundary in different doses of SCP groups became clear, the areas were increased, and the number cells was increased significantly. Conclusion: SCP can decrease the FBG level, increase the INS level and improve insulin resistance (IR) in the T2DM rats induced by high-fat diet combined with low dose of STZ, and its mechanism might be related to its inhibiting inflammation response.

Key words: Schisandra chinensis polysaccharide, type 2 diabetes mellieus, inflammatory factors, high-fat diet, streptozotocin, fasting blood glucose

中图分类号:

R587.1

杜兴旭, 乔子敬, 杨硕, 许智莹, 杨波, 李贺, 陈建光, 王春梅. 五味子多糖对2型糖尿病大鼠血清中炎症因子的影响及其作用机制[J]. 吉林大学学报(医学版), 2020, 46(01): 50-55.

DU Xingxu, QIAO Zijing, YANG Shuo, XU Zhiying, YANG Bo, LI He, CHEN Jianguang, WANG Chunmei. Effect of Schisandra chinensis polysaccharide on serum inflammatory factors in T2DM rats and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2020, 46(01): 50-55.

参考文献

[1] HOTAMISLIGIL G S. Inflammation and metabolic disorders[J]. Nature, 2006, 444(7121):860-867.
[2] DONATH M Y, SHOELSON S E. Type 2 diabetes as an inflammatory disease[J]. Nat Rev Immunol, 2011, 11(2):98-107.
[3] XI L, XIAO C, BANDSMA R. C-reactive protein impairs hepatic activated protein kinases[J]. Hepatology, 2011, 53(1):127-135.
[4] FASSHAUER M, BLVHER M. Adipokines in health and disease[J]. Trends Pharmacol Sci, 2015, 36(7):461-470.
[5] RABE K, LEHRKE M, PARHOFER K G, et al. Adipokines and insulin resistance[J]. Mol Med, 2008, 14(11/12):741-751.
[6] FENG Y H, CHEN L, LUO Q, et al. Involvement of microRNA-146a in diabetic peripheral neuropathy through the regulation of inflammation[J]. Drug Des Devel Ther, 2018, 12:171-177.
[7] WANG N, XU T Y, ZHANG X, et al. Improving hyperglycemic effect of FGF-21 is associated with alleviating inflammatory state in diabetes[J]. Int Immunopharmacol, 2018, 56:301-309.
[8] 雍履平. 五味子治疗糖尿病功效卓著[J]. 中医杂志, 1998, 39(7):389.
[9] JIN D, ZHAO T, FENG W W, et al. Schisandra polysaccharide increased glucose consumption by up-regulating the expression of GLUT-4[J]. Int J Biol Macromol, 2016, 87:555-562.
[10] AN L P, WANG Y P, WANG C M, et al. Protective effect of Schisandrae chinensis oil on pancreatic β-cells in diabetic rats[J]. Endocrine, 2015, 48(3):818-825.
[11] WANG C M, YUAN R S, ZHUANG W Y, et al. Schisandra polysaccharide inhibits hepatic lipid accumulation by downregulating expression of SREBPs in NAFLD mice[J]. Lipids Health Dis, 2016, 15(1):195.
[12] PARK H J, LEE S J, SONG Y, et al. Schisandra chinensis prevents alcohol-induced fatty liver disease in rats[J]. J Med Food, 2014, 17(1):103-110.
[13] YUAN R S, TAO X, LIANG S, et al. Protective effect of acidic polysaccharide from Schisandra chinensis on acute ethanol-induced liver injury through reducing CYP2E1-dependent oxidative stress[J]. Biomed Pharmacother, 2018, 99:537-542.
[14] TAO X, LIANG S, CHE J, et al. Antidiabetic activity of acidic polysaccharide from schisandra chinensisin STZ-Induced diabetic mice[J]. Nat Prod Commun,2019,14(6).DOI:10.1177/1934578X19850374.
[15] ZHANG M, LV X Y, LI J, et al. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model[J]. Exp Diabetes Res, 2008, 2008:704045.
[16] VEERAPUR V P, PRABHAKAR K R, THIPPESWAMY B S, et al. Antidiabetic effect of Ficus racemosa Linn. stem bark in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats:A mechanistic study[J]. Food Chem, 2012, 132(1):186-193.
[17] 张志军. 五味子治疗糖尿病的效果[J]. 国外医学:中医中药分册, 1994, 16(3):27-28.
[18] NIU J M, XU G Y, JIANG S, et al. In vitro antioxidant activities and anti-diabetic effect of a polysaccharide from Schisandra sphenanthera in rats with type 2 diabetes[J]. Int J Biol Macromol, 2017, 94(Pt A):154-160.
[19] AKASH M S, REHMAN K, CHEN S Q. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus[J]. J Cell Biochem, 2013, 114(3):525-531.
[20] KOHLGRUBER A, LYNCH L. Adipose tissue inflammation in the pathogenesis of type 2 diabetes[J]. Curr Diab Rep, 2015, 15(11):92.
[21] HOTAMISLIGIL G S, SHARGILL N S, SPIEGELMAN B M. Adipose expression of tumor necrosis factor-α:direct role in obesity-linked insulin resistance[J]. Science, 1993, 259(5091):87-91.
[22] LUMENG C N, BODZIN J L, SALTIEL A R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization[J]. J Clin Invest, 2007, 117(1):175-184.
[23] EGUCHI K, NAGAI R. Islet inflammation in type 2 diabetes and physiology[J]. J Clin Invest, 2017, 127(1):14-23.
[24] MARCHETTI P. Islet inflammation in type 2 diabetes[J]. Diabetologia, 2016, 59(4):668-672.
[25] EGUCHI K, MANABE I. Macrophages and islet inflammation in type 2 diabetes[J]. Diabetes Obes Metab, 2013, 15(Suppl):152-158.
[26] LONTCHI Y, SOBNGWI E, MATSHAT E, et al. Diabetes Mellitus and Inflammation[J]. Curr Diab Rep, 2013, 13(3):435-444.
[27] LARSEN C M, FAULENBACH M,VAAG A,et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus[J]. N Engl J Med, 2007, 356(15):1517-1526.
[28] SLOAN-LANCASTER J,ABU-BADDADE,POLZER J,et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1β antibody, in patients with type 2 diabetes[J]. Diabetes Care, 2013, 36(8):2239-2246.
[29] GOLDFINE A B,FONSECA V, JABLONSKI K A,et al. Salicylate (salsalate) in patients with type 2 diabetes:A randomized trial[J]. Ann Intern Med, 2013, 159(1):1-12.