摘要
目的观察外源性给予apelin-13对糖尿病鼠氧化应激及心肌炎性因子和细胞凋亡的影响。方法40只雄性Wistar大鼠适应性喂养1周后,随机分成对照组8只,实验组32只。实验组通过高糖高脂饮食喂养8周联合链脲佐菌素(STZ)1次性腹腔注射30mg/kg,造2型糖尿病模型。造模成功的28只大鼠随机分成模型组(14只),给药组(14只)。给药组给予apelin-130.1tzmol·kg^-1·d^-1腹腔注射,对照组和糖尿病组给予0.9%氯化钠溶液等体积注射连续给药10周。10周末取材。比色法测定过氧化氢(H2O2)、-氧化氮(NO)、丙二醛(MDA),酶联免疫吸附实验(ELISA)测定超氧化物歧化酶(SOD),免疫组化法比较各组大鼠心肌白介素6(IL-6)、肿瘤坏死因子-α(TNF—α)表达,原位细胞凋亡检测法(TUNEL)比较心肌细胞凋亡程度,Masson染色法比较心肌纤维化程度。结果模型组大鼠MDA、H2O2、NO水平增高(F=22.400、6.230、4.247,P〈0.0167),模型组SOD较对照组水平降低(F=8.901,P〈0.0167)。apelin-13干预后,MDA、H2O2、SOD分别较模型组变化显著,NO变化不明显。模型组大鼠心肌组织TNF—α(0.0599±0.0208)、IL-6(0.0503±0.0243)较对照组(0.0076±0.0031、0.0071±0.0024)表达增加(F-35.139、15.946,P〈0.016),治疗后,给药组大鼠心肌组织中炎性因子表达水平较模型组降低。心肌细胞凋亡数模型组(0.0293±0.0061)较对照组(0.0030±0.0013)增加(F=84.930,P〈0.0167),给药组(0.0158±0.0055)较模型组减少。心肌纤维化程度模型组(0.0708±0.0420)较对照组(0.0013±0.0003)变化显著(F=19.420,P〈0.0167),给药组(0.0077±0.0044)较模型组纤维化程度明显改善。结论apelin-13在-定程度上减轻2型糖尿病氧化应激水平、心肌炎症反应,对心肌细胞凋亡和纤维化有改善作用。
Objective To investigate the effect of exogenous apeliw13 on oxidative stress, myocardial inflammatory cytokines and apoptosis in diabetic model rats. Methods A total of 40 male Wistar rats were randomly divided into 2 groups: normal control group (NC, n = 8) and experimental group (EX, n= 32). Diabetes was induced by feeding with high-sugary and high-fat diet for 8 weeks and a single intraperitoneal injection of streptozotoein (STZ) (30 mg/kg). The well- established 28 diabetic model rats were then randomly divided into 2 subgroups: model group (DM, n = 14) and apelin-13 administration group (AP, n = 14). The rats in AP group were given intraperitoneal administration of apelin-13 at a single dose of 0. 1 μmol ·kg^-1· d^-1 for 10 weeks, while NC group and DM group were given 0.9 % NaC1 in the same way. All rats were sacrificed at the end of the week 10. Blood hydrogen peroxide (H2O2), nitric oxide (NO) and malonaldehyde (MDA) were measured by colorimetry, and superoxide dismutase (SOD) was measured by enzyme-linked immunosorbent assay (ELISA). The expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rat myocardium were detected by immunohistoehemistry. Masson staining was used to observe the myocardial fibrosis in rats of different groups. Cardiomyocyte apoptosis was determined by TUNEL. Results (1) Compared with NC groups, DM group showed that MDA, H2O2and NOwere significantly increased, while SOD was significantly decreased (F=22. 400, 6. 230, 4. 267 and 8. 901, all P〈0. 0167). There was a statistically significant difference in the levels of MDA, H2O2, SOD between DM group and AP group. (2) The expression of TNF-α and II.-6 was significantly higher inDMgroup than inNCgroup (0.0599±0.0208 vs. 0.0076±0.0031, F=35.139; 0.0503±0.0243 ± 0. 0071 ± 0. 0024, F= 15. 946, both P〈0. 0167). After 10 weeks of apelin-13 administration, the levels of inflammatory cytokines were significantly decreased in AP group than in DM group. (3) The myocardial apoptosis and fibrosis were significantly increased in DM group than in NCgroup 〈0.0293±0.0061 vs. 0.0030±0.0013 and 0.0708±0.0420 vs. 0.0013±0.0003, F= 84. 930 and 19. 420, both P〈0. 01671. The myocardial apoptosis and fibrosis were significantly decreased in AP group than in DM group (both P〈0. 0167). Conclusions To some extent, apelin- 13 reduces the levels of oxidative stress and myocardial inflammation reaction in type 2 diabetes. Moreover, it may play a vital role in the improvement of myocardial apoptosis and fibrosis.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2016年第1期85-90,共6页
Chinese Journal of Geriatrics
基金
哈尔滨市科技创新人才研究专项资金项目(2012RFXXSO50)
关键词
糖尿病
细胞凋亡
肌细胞
心脏
脂肪因子
Diabetes mellitus
Apoptosis
Myocytes, cardiac
Adipokines