抗菌肽Dybowskin-2CDYa促胰岛素分泌及对二型糖尿病大鼠的降血糖和治疗效果

发布时间：2018-03-14 03:50

  本文选题：抗菌肽Dybowskin-2CDYa　切入点：促胰岛素分泌　出处：《辽宁大学》2015年硕士论文　论文类型：学位论文

【摘要】：抗菌肽(antimicrobial peptides)是小分子多肽,具有热稳定性强、抗原性低、抗菌谱广的优点。随着研究的深入,多种两栖动物来源的抗菌肽被发现具有促胰岛素分泌功能。这种抗菌肽与传统降糖药物比较具有体内不易降解且仅在高糖环境中促进胰岛细胞增殖从而降低血糖的优势,被认为是高效安全治疗Ⅱ型糖尿病的潜在药物。从东北林蛙皮肤表面分离得到一系列新型抗菌肽,并对其中一条名为Dybowskin-2CDYa(SAVGRHGRRFGLRKHRKH)。前期研究工作表明,Dybowskin-2CDYa类似物对小鼠胰岛MIN6细胞具有较好的促胰岛素分泌作用,但Dybowskin-2CDya的作用尚不明确。本研究利用ELISA和CCK-8实验,分析了抗菌肽Dybowskin-2CDYa对小鼠胰岛细胞促胰岛素分泌及增殖作用的影响,结果表明,与对照组相比,Dybowskin-2CDYa具有显著的促MIN6细胞胰岛素分泌和细胞增殖作用。同时,利用链脲佐菌素STZ构建了Ⅱ型糖尿病大鼠模型,分析了抗菌肽Dybowskin-2CDya对糖尿病大鼠的降糖作用,结果表明,腹腔注射100nmol/L抗菌肽Dybowskin-2CDYa,Ⅱ型糖尿病模型大鼠30min时血糖开始下降,到210min时,血糖基本达到正常水平,具有显著降糖作用。正常组大鼠腹腔注射同样浓度的抗菌肽Dybowskin-2CDYa,180min血糖仍维持在正常水平,表明抗菌肽Dybowskin-2CDYa仅在高糖条件下发挥降糖作用,不会导致低血糖。本研究进一步利用HE染色技术,探讨了抗菌肽Dybowskin-2CDYa对Ⅱ型糖尿病大鼠肝脏、胰岛组织的保护作用,肝组织切片的HE染色结果表明,抗菌肽Dybowskin-2CDYa干预组与糖尿病模型组相比,大鼠肝组织中细胞间隙减少,肿大肝细胞数目减少,肝细胞中空泡减少,脂肪变性程度降低,正常肝细胞数目较未干预组有所恢复。肝和胰岛组织BAX和BCL-2蛋白免疫组化结果表明,抗菌肽Dybowskin-2CDYa能上调BCL-2蛋白表达,下调BAX蛋白表达,从而抑制肝、胰岛细胞凋亡,对肝和胰岛起保护作用。
[Abstract]:Antimicrobial peptide is a small polypeptide with high thermal stability, low antigenicity and wide antibacterial spectrum. Antimicrobial peptides from various amphibian sources have been found to promote insulin secretion. This antimicrobial peptide has an advantage over traditional hypoglycemic drugs in that it is not degradable in vivo and only promotes the proliferation of islet cells in high glucose environments, thereby reducing blood glucose. A series of new antimicrobial peptides have been isolated from the skin surface of Rana forest frog in Northeast China, which is considered to be a potential drug for the safe and efficient treatment of type 2 diabetes. One of them, named Dybowskin-2CDYaA, SAVGRHGRRFGLRKHRKHHHN, was used to induce insulin secretion in murine islet MIN6 cells, but the effect of Dybowskin-2CDya was not clear. In this study, ELISA and CCK-8 experiments were used to investigate the effect of dybowskin-2CDYa analogue on insulin secretion of mouse pancreatic islet MIN6 cells. The effects of antimicrobial peptide Dybowskin-2CDYa on insulin secretion and proliferation of mouse islet cells were analyzed. The results showed that dybowskin-2CDYa could significantly promote insulin secretion and proliferation of MIN6 cells compared with control group. A rat model of type 鈪，

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