瑞格列奈的抗氧化和抗炎作用研究
發(fā)布時間：2018-10-30 08:43
【摘要】：隨著人們生活水平的提高，糖尿病的發(fā)病率越來越高，嚴重威脅著人類的健康和生活質(zhì)量。有研究報道氧化應(yīng)激和炎癥是引起糖尿病及其并發(fā)癥的主要病理生理因素；臨床常用劑量瑞格列奈可以改善Ⅱ型糖尿病患者氧化應(yīng)激及炎癥相關(guān)指標；瑞格列奈為苯甲酸類衍生物，其結(jié)構(gòu)決定其可能具有抗氧化作用。本實驗通過建立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與促進胰島素的分泌、降糖作用及抗氧化作用的相關(guān)性，為臨床上更合理的使用瑞格列奈提供依據(jù)。 本文采用一次性大劑量腹腔注射STZ建立Ⅰ型糖尿病模型，取雄性SD大鼠隨機分為正常對照組、正常給藥組（1mg/kg）、模型組、瑞格列奈組（1mg/kg）、吲哚美辛組（5mg/kg）。正常對照組、模型組給予等體積0.5%CMC-Na。給藥期間，觀察大鼠的活動狀態(tài)，兩天測定一次大鼠體重，每周測定一次大鼠攝食量、飲水量和空腹血糖。給藥4周后各組處理一半動物、給藥8周后處理剩余動物，取各組大鼠的主要臟器并計算臟器系數(shù)；測定血清中胰島素水平；檢測氧化應(yīng)激相關(guān)指標SOD、MDA、GSH、H2O2；檢測血清中CRP、TNF-α、IL-6、NF-κB、AP-1的水平。 結(jié)果顯示，（1）給藥4周后，與模型組比，瑞格列奈組的大鼠體重，空腹血糖、胰島素水平、攝食量、飲水量、胸腺、脾臟、肝臟、心臟、腎臟、附睪周圍脂肪指數(shù)IL-6均無顯著變化；血清中SOD活性、GSH水平明顯升高（p0.05）；血清中的H2O2、MDA、CRP、TNF-α、NF-κB、AP-1水平明顯降低（p0.05）。正常給藥組與正常對照組比各指標無明顯變化。（2）給藥8周后，，瑞格列奈組的血清中的H2O2、MDA、CRP、TNF-α、NF-κB、AP-1水平顯著低于模型組（p0.05）；血清中SOD活性、GSH水平明顯高于模型組（p0.05）；大鼠體重，空腹血糖、胰島素水平、攝食量、飲水量、胸腺、脾臟、肝臟、心臟、腎臟、附睪周圍脂肪指數(shù)IL-6與模型組無顯著差異；瑞格列奈對正常大鼠的各指標無明顯作用。 本實驗結(jié)果表明瑞格列奈具有抗氧化作用、抗炎作用且獨立于降血糖作用，抗炎作用主要與其抗氧化作用相關(guān)，可能是通過抑制NF-κB、AP-1的表達，進一步抑制炎癥因子的釋放而發(fā)揮抗炎作用。
[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- 偽, 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- 偽 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- 偽 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.
【學(xué)位授予單位】：北京理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1
本文編號：2299514
[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- 偽, 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- 偽 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- 偽 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.
【學(xué)位授予單位】：北京理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1
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