消退素D1抑制肝臟p38MAPK活化改善2型糖尿病小鼠胰島素抵抗的研究
發(fā)布時間：2018-08-19 16:41
【摘要】：目的:胰島素抵抗是2型糖尿病的重要發(fā)病機制之一,目前認為胰島素抵抗是一種慢性低度炎癥,近期發(fā)現(xiàn),ω-3多不飽和脂肪酸的衍生物—消退素是一種新型的抗炎介質(zhì),其在慢性炎癥中有著“剎車信號”的作用。消退素D1(RVD1)是消退素中的重要一員,那么RVD1是否可以通過抗炎作用改善2型糖尿病小鼠的胰島素抵抗以及其機制是什么?為了明確上述問題,我們進行了此項研究。方法:選取35只C57BL/6雄性小鼠,高脂喂養(yǎng)結(jié)合單次腹腔注射小劑量鏈脲佐菌素(Streptozotocin,STZ)建立具有胰島素抵抗的2型糖尿病小鼠模型,隨機分為空白對照組(Con組)、2型糖尿病組(T2DM組)、2型糖尿病+RVD1干預(yù)組(T2DM+RVD1組),RVD1干預(yù)21天,期間定期檢測小鼠體重及血糖,實驗結(jié)束后取血測甘油三酯、總膽固醇、胰島素水平,以及計算胰島素抵抗指數(shù),取血后迅速解剖小鼠,留取新鮮肝臟組織用于檢測TNF-α、IL-6、p38MAPK、pp38MAPK的水平。結(jié)果:1小鼠一般情況的變化Con組小鼠一直維持良好的精神狀態(tài),亮澤的毛發(fā),靈活的活動,飲食、大便、小便無異常,未見死亡;T2DM組和T2DM+RVD1組小鼠精神狀態(tài)欠佳,有多尿、多飲、多食等糖尿病的相關(guān)癥狀,毛發(fā)黯淡無光,行動緩慢。但與T2DM組小鼠比較,T2DM+RVD1組小鼠上述情況均有所改善。Con組小鼠體重緩慢增長;T2DM組和T2DM+RVD1組在造模前體重增加迅速,造模后體重增長相對緩慢。與Con組相比,T2DM組和T2DM+RVD1組小鼠體重明顯增加,差異有統(tǒng)計學意義(P0.05)。與T2DM組相比,T2DM+RVD1組體重在RVD1干預(yù)1周前無明顯差異,在RVD1干預(yù)2周后,T2DM+RVD1組體重有所下降,差異有統(tǒng)計學意義(P0.05)。2小鼠生化指標和胰島素抵抗指標的變化2.1小鼠血糖的變化Con組小鼠血糖維持正常水平,T2DM組和T2DM+RVD1組血糖在應(yīng)用高脂飼料喂養(yǎng)8周后出現(xiàn)糖調(diào)節(jié)受損,造模后血糖升高更明顯。與Con組相比較,T2DM組及T2DM+RVD1組小鼠血糖明顯升高,尤其是建立2型糖尿病模型后,差異有統(tǒng)計學意義(P0.05)。與T2DM組相比,T2DM+RVD1組血糖在RVD1干預(yù)1周之前血糖無明顯變化,差異無統(tǒng)計學意義(P0.05)。但是在RVD1干預(yù)2周后,T2DM+RVD1組小鼠血糖較T2DM組有所降低,差異有統(tǒng)計學意義(P0.05)。2.2小鼠血脂的變化與Con組相比較,T2DM組及T2DM+RVD1組小鼠總膽固醇及甘油三酯升高,差異有統(tǒng)計學意義(P0.05)。與T2DM組相比較,T2DM+RVD1組小鼠總膽固醇及甘油三酯有所降低,差異有統(tǒng)計學意義(P0.05)。2.3血清胰島素水平變化與Con組相比較,T2DM及T2DM+RVD1組小鼠胰島素水平明顯升高,差異有統(tǒng)計學意義(P0.05)。與T2DM組相比較,T2DM+RVD1組小鼠的胰島素水平有所降低,差異有統(tǒng)計學意義(P0.05)。2.4胰島素抵抗指數(shù)的變化與Con組相比較,T2DM及T2DM+RVD1組小鼠胰島素抵抗指數(shù)高,差異有統(tǒng)計學意義(P0.05)。與T2DM組相比較,T2DM+RVD1組小鼠胰島素抵抗指數(shù)明顯降低,差異有有統(tǒng)計學意義(P0.05)。3小鼠肝臟炎性指標的變化3.1小鼠肝臟IL-6、TNF-α水平的變化與Con組相比較,T2DM及T2DM+RVD1組小鼠肝臟中TNF-α、IL-6升高,差異有統(tǒng)計學意義(P0.05)。與T2DM組相比較,T2DM+RVD1組小鼠肝臟中TNF-α、IL-6降低,差異有統(tǒng)計學意義(P0.05)。3.2小鼠肝臟組織中p38MAPK活化水平。與Con組相比較,T2DM及T2DM+RVD1組小鼠肝臟中pp38MAPK/p38MAPk比值升高,差異有統(tǒng)計學意義(P0.05)。與T2DM組相比較,T2DM+RVD1組小鼠肝臟中pp38MAPK/p38MAPK比值降低,差異有統(tǒng)計學意義(P0.05)。結(jié)論:1 RVD1降低2型糖尿病小鼠的體重、血糖、甘油三酯、總膽固醇、胰島素以及胰島素抵抗指數(shù),改善了2型糖尿病小鼠的胰島素抵抗。2 RVD1降低了肝臟中炎癥因子TNF-α、IL-6水平,改善了肝臟的胰島素抵抗。3 RVD1可能通過抑制了肝臟中p38MAPK炎癥信號的通路,減少了肝臟炎癥因子的產(chǎn)生,改善了肝臟的胰島素抵抗。
[Abstract]:OBJECTIVE: Insulin resistance is one of the important pathogenesis of type 2 diabetes mellitus. Insulin resistance is currently considered to be a chronic low-grade inflammation. Recently, it has been found that_-3 polyunsaturated fatty acid derivative, receptionin, is a new anti-inflammatory mediator and plays a role of "brake signal" in chronic inflammation. To clarify these questions, we conducted this study. METHODS: Thirty-five male C57BL/6 mice were fed with high fat diet combined with a single intraperitoneal injection of low dose streptozotocin (STZ). The model of type 2 diabetes mellitus with insulin resistance was established and randomly divided into control group (Con group), type 2 diabetes mellitus group (T2DM group), type 2 diabetes mellitus + RVD1 intervention group (T2DM + RVD1 group) and RVD1 intervention group (T2DM + RVD1 group). The body weight and blood glucose of the mice were measured regularly during the intervention period of 21 days. Result: 1. The mice in the Con group had maintained good mental state, bright hair, flexible movement, diet, stool and urine without abnormalities, and no death was observed in the T2DM group and the T2DM + RVD1 group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. Compared with the control group, the weight of mice in T2DM group and T2DM+RVD1 group increased significantly (P 0.05). Compared with the T2DM group, the weight of mice in T2DM+RVD1 group had no significant difference before RVD1 intervention for one week. After RVD1 intervention for two weeks, the weight of mice in T2DM+RVD1 group decreased, and the difference was statistically significant (P 0.05). The blood glucose level of Con group and T2DM+RVD1 group was normal. The glucose regulation of T2DM group and T2DM+RVD1 group was impaired after 8 weeks feeding with high fat diet, and the blood glucose increased more significantly after modeling. Compared with Con group, the blood glucose of T2DM group and T2DM+RVD1 group increased significantly, especially after the establishment of type 2 diabetes mellitus model. Compared with T2DM group, the blood glucose of T2DM + RVD1 group had no significant change before RVD1 intervention for 1 week (P 0.05). But after RVD1 intervention for 2 weeks, the blood glucose of T2DM + RVD1 group was lower than that of T2DM group, and the difference was statistically significant (P 0.05). The total cholesterol and triglyceride levels of mice in T2DM + RVD1 group were lower than those in T2DM group (P 0.05). 2.3 Serum insulin levels in T2DM and T2DM + RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with the T2DM group, the insulin level of the T2DM + RVD1 group was lower, and the difference was statistically significant (P 0.05). The insulin resistance index of the T2DM + RVD1 group was higher than that of the Con group (P 0.05). Compared with the T2DM + RVD1 group, the insulin resistance index of the T2DM + RVD1 group was higher, and the difference was statistically significant (P 0.05). The levels of IL-6 and TNF-alpha in liver of mice in T2DM and T2DM+RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with T2DM group, the levels of TNF-alpha and IL-6 in liver of mice in T2DM+RVD1 group were significantly higher (P 0.05). Compared with the control group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM and T2DM + RVD1 groups was higher (P 0.05). Compared with the T2DM group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM + RVD1 group was lower (P Conclusion: 1 RVD1 can decrease body weight, blood glucose, triglyceride, total cholesterol, insulin and insulin resistance index in type 2 diabetic mice, and improve insulin resistance in type 2 diabetic mice. APK inflammatory signaling pathway reduces the production of liver inflammatory factors and improves insulin resistance in the liver.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R587.1
本文編號：2192229
[Abstract]:OBJECTIVE: Insulin resistance is one of the important pathogenesis of type 2 diabetes mellitus. Insulin resistance is currently considered to be a chronic low-grade inflammation. Recently, it has been found that_-3 polyunsaturated fatty acid derivative, receptionin, is a new anti-inflammatory mediator and plays a role of "brake signal" in chronic inflammation. To clarify these questions, we conducted this study. METHODS: Thirty-five male C57BL/6 mice were fed with high fat diet combined with a single intraperitoneal injection of low dose streptozotocin (STZ). The model of type 2 diabetes mellitus with insulin resistance was established and randomly divided into control group (Con group), type 2 diabetes mellitus group (T2DM group), type 2 diabetes mellitus + RVD1 intervention group (T2DM + RVD1 group) and RVD1 intervention group (T2DM + RVD1 group). The body weight and blood glucose of the mice were measured regularly during the intervention period of 21 days. Result: 1. The mice in the Con group had maintained good mental state, bright hair, flexible movement, diet, stool and urine without abnormalities, and no death was observed in the T2DM group and the T2DM + RVD1 group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. The mice in the T2DM + RVD1 group had slower weight gain than those in the T2DM group. Compared with the control group, the weight of mice in T2DM group and T2DM+RVD1 group increased significantly (P 0.05). Compared with the T2DM group, the weight of mice in T2DM+RVD1 group had no significant difference before RVD1 intervention for one week. After RVD1 intervention for two weeks, the weight of mice in T2DM+RVD1 group decreased, and the difference was statistically significant (P 0.05). The blood glucose level of Con group and T2DM+RVD1 group was normal. The glucose regulation of T2DM group and T2DM+RVD1 group was impaired after 8 weeks feeding with high fat diet, and the blood glucose increased more significantly after modeling. Compared with Con group, the blood glucose of T2DM group and T2DM+RVD1 group increased significantly, especially after the establishment of type 2 diabetes mellitus model. Compared with T2DM group, the blood glucose of T2DM + RVD1 group had no significant change before RVD1 intervention for 1 week (P 0.05). But after RVD1 intervention for 2 weeks, the blood glucose of T2DM + RVD1 group was lower than that of T2DM group, and the difference was statistically significant (P 0.05). The total cholesterol and triglyceride levels of mice in T2DM + RVD1 group were lower than those in T2DM group (P 0.05). 2.3 Serum insulin levels in T2DM and T2DM + RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with the T2DM group, the insulin level of the T2DM + RVD1 group was lower, and the difference was statistically significant (P 0.05). The insulin resistance index of the T2DM + RVD1 group was higher than that of the Con group (P 0.05). Compared with the T2DM + RVD1 group, the insulin resistance index of the T2DM + RVD1 group was higher, and the difference was statistically significant (P 0.05). The levels of IL-6 and TNF-alpha in liver of mice in T2DM and T2DM+RVD1 groups were significantly higher than those in Con group (P 0.05). Compared with T2DM group, the levels of TNF-alpha and IL-6 in liver of mice in T2DM+RVD1 group were significantly higher (P 0.05). Compared with the control group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM and T2DM + RVD1 groups was higher (P 0.05). Compared with the T2DM group, the ratio of pp38MAPK / p38MAPK in the liver of T2DM + RVD1 group was lower (P Conclusion: 1 RVD1 can decrease body weight, blood glucose, triglyceride, total cholesterol, insulin and insulin resistance index in type 2 diabetic mice, and improve insulin resistance in type 2 diabetic mice. APK inflammatory signaling pathway reduces the production of liver inflammatory factors and improves insulin resistance in the liver.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R587.1
【參考文獻】
相關(guān)期刊論文 前3條
1 張毅;李慧穎;董玲;高峰;;鏈脲佐菌素誘導(dǎo)模擬2型糖尿病動物模型的研究進展[J];中華糖尿病雜志;2011年05期
2 姜驪;陳輝;何勇;魚達;;高脂飲食加低劑量鏈脲霉素建立小鼠2型糖尿病模型[J];中國比較醫(yī)學雜志;2010年03期
3 張山佳,丁樹哲;2型糖尿病發(fā)病機制研究:腫瘤壞死因子α與胰島素抵抗的關(guān)系[J];中國臨床康復(fù);2005年07期
，本文編號：2192229
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