瑞格列奈的抗氧化和抗炎作用研究

发布时间：2018-10-30 08:43

【摘要】：随着人们生活水平的提高，糖尿病的发病率越来越高，严重威胁着人类的健康和生活质量。有研究报道氧化应激和炎症是引起糖尿病及其并发症的主要病理生理因素；临床常用剂量瑞格列奈可以改善Ⅱ型糖尿病患者氧化应激及炎症相关指标；瑞格列奈为苯甲酸类衍生物，其结构决定其可能具有抗氧化作用。本实验通过建立Ⅰ型糖尿病模型，探索瑞格列奈是否具有抗氧化和抗炎作用，瑞格列奈的抗炎作用与促进胰岛素的分泌、降糖作用及抗氧化作用的相关性，为临床上更合理的使用瑞格列奈提供依据。本文采用一次性大剂量腹腔注射STZ建立Ⅰ型糖尿病模型，取雄性SD大鼠随机分为正常对照组、正常给药组（1mg/kg）、模型组、瑞格列奈组（1mg/kg）、吲哚美辛组（5mg/kg）。正常对照组、模型组给予等体积0.5%CMC-Na。给药期间，观察大鼠的活动状态，两天测定一次大鼠体重，每周测定一次大鼠摄食量、饮水量和空腹血糖。给药4周后各组处理一半动物、给药8周后处理剩余动物，取各组大鼠的主要脏器并计算脏器系数；测定血清中胰岛素水平；检测氧化应激相关指标SOD、MDA、GSH、H2O2；检测血清中CRP、TNF-α、IL-6、NF-κB、AP-1的水平。结果显示，（1）给药4周后，与模型组比，瑞格列奈组的大鼠体重，空腹血糖、胰岛素水平、摄食量、饮水量、胸腺、脾脏、肝脏、心脏、肾脏、附睾周围脂肪指数IL-6均无显著变化；血清中SOD活性、GSH水平明显升高（p0.05）；血清中的H2O2、MDA、CRP、TNF-α、NF-κB、AP-1水平明显降低（p0.05）。正常给药组与正常对照组比各指标无明显变化。（2）给药8周后，，瑞格列奈组的血清中的H2O2、MDA、CRP、TNF-α、NF-κB、AP-1水平显著低于模型组（p0.05）；血清中SOD活性、GSH水平明显高于模型组（p0.05）；大鼠体重，空腹血糖、胰岛素水平、摄食量、饮水量、胸腺、脾脏、肝脏、心脏、肾脏、附睾周围脂肪指数IL-6与模型组无显著差异；瑞格列奈对正常大鼠的各指标无明显作用。本实验结果表明瑞格列奈具有抗氧化作用、抗炎作用且独立于降血糖作用，抗炎作用主要与其抗氧化作用相关，可能是通过抑制NF-κB、AP-1的表达，进一步抑制炎症因子的释放而发挥抗炎作用。
[Abstract]:With the improvement of people's living standard, the incidence of diabetes is becoming higher and higher, which is a serious threat to human health and quality of life. It has been reported that oxidative stress and inflammation are the main pathophysiological factors causing diabetes mellitus and its complications. Repaglinide is a benzoic acid derivative, its structure may have antioxidant effect. In this study, the model of type I diabetes mellitus was established to explore whether repaglinide has antioxidant and anti-inflammatory effects, and the correlation between the anti-inflammatory effect of repaglinide and the promotion of insulin secretion, hypoglycemic and antioxidant effects. It provides evidence for rational use of rieglinide in clinic. The model of type I diabetes was established by intraperitoneal injection of STZ at a single large dose. Male SD rats were randomly divided into normal control group, normal administration group (1mg/kg), model group, repaglinide group (1mg/kg). Indomethacin group (5mg/kg). Normal control group and model group were given equal volume 0.5% CMC-Na. During the administration, the active state of the rats was observed, the body weight was measured once a day, and the intake, drinking water and fasting blood glucose were measured once a week. After 4 weeks of administration, half of the animals were treated in each group, and the remaining animals were treated after 8 weeks of administration. The main organs of the rats in each group were taken and the organ coefficients were calculated; the serum insulin level was measured; and the indexes related to oxidative stress (SOD,MDA,GSH,H2O2;) were detected. The serum levels of CRP,TNF- 伪, IL-6,NF- 魏 B and AP-1 were measured. The results showed that: (1) after 4 weeks of administration, the body weight, fasting blood glucose, insulin level, food intake, water intake, thymus, spleen, liver, heart, kidney, liver, heart and kidney of rats in the repaglinide group were higher than those in the model group. There was no significant change in the periepididymal fat index (IL-6). The activity of SOD and the level of GSH in serum were significantly increased (p0.05), and the levels of TNF- 伪 and NF- 魏 BmAP-1 in serum were significantly decreased (p0.05). (2) after 8 weeks of administration, the levels of H _ 2O _ 2 MDA-CRPN- 伪 and NF- 魏 B _ (AP-1) in serum in the repaglinide group were significantly lower than those in the model group (p0.05). The activity of SOD and the level of GSH in serum were significantly higher than those in the model group (p0. 05). There was no significant difference in body weight, fasting blood glucose, insulin level, intake, drinking water, thymus, spleen, liver, heart, kidney, periepididymal fat index (IL-6) between the model group and the model group. Repaglinide had no obvious effect on the indexes of normal rats. The results showed that repaglinide had antioxidant effect, anti-inflammatory effect and independent of hypoglycemic effect. The anti-inflammatory effect was mainly related to its anti-oxidation effect, possibly by inhibiting the expression of NF- 魏 BnAP-1. Further inhibit the release of inflammatory factors and play an anti-inflammatory effect.
【学位授予单位】：北京理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

【参考文献】