發(fā)布時間：2018-03-14 03:50

  本文選題：抗菌肽Dybowskin-2CDYa　切入點：促胰島素分泌　出處：《遼寧大學》2015年碩士論文　論文類型：學位論文

【摘要】：抗菌肽(antimicrobial peptides)是小分子多肽,具有熱穩(wěn)定性強、抗原性低、抗菌譜廣的優(yōu)點。隨著研究的深入,多種兩棲動物來源的抗菌肽被發(fā)現具有促胰島素分泌功能。這種抗菌肽與傳統(tǒng)降糖藥物比較具有體內不易降解且僅在高糖環(huán)境中促進胰島細胞增殖從而降低血糖的優(yōu)勢,被認為是高效安全治療Ⅱ型糖尿病的潛在藥物。從東北林蛙皮膚表面分離得到一系列新型抗菌肽,并對其中一條名為Dybowskin-2CDYa(SAVGRHGRRFGLRKHRKH)。前期研究工作表明,Dybowskin-2CDYa類似物對小鼠胰島MIN6細胞具有較好的促胰島素分泌作用,但Dybowskin-2CDya的作用尚不明確。本研究利用ELISA和CCK-8實驗,分析了抗菌肽Dybowskin-2CDYa對小鼠胰島細胞促胰島素分泌及增殖作用的影響,結果表明,與對照組相比,Dybowskin-2CDYa具有顯著的促MIN6細胞胰島素分泌和細胞增殖作用。同時,利用鏈脲佐菌素STZ構建了Ⅱ型糖尿病大鼠模型,分析了抗菌肽Dybowskin-2CDya對糖尿病大鼠的降糖作用,結果表明,腹腔注射100nmol/L抗菌肽Dybowskin-2CDYa,Ⅱ型糖尿病模型大鼠30min時血糖開始下降,到210min時,血糖基本達到正常水平,具有顯著降糖作用。正常組大鼠腹腔注射同樣濃度的抗菌肽Dybowskin-2CDYa,180min血糖仍維持在正常水平,表明抗菌肽Dybowskin-2CDYa僅在高糖條件下發(fā)揮降糖作用,不會導致低血糖。本研究進一步利用HE染色技術,探討了抗菌肽Dybowskin-2CDYa對Ⅱ型糖尿病大鼠肝臟、胰島組織的保護作用,肝組織切片的HE染色結果表明,抗菌肽Dybowskin-2CDYa干預組與糖尿病模型組相比,大鼠肝組織中細胞間隙減少,腫大肝細胞數目減少,肝細胞中空泡減少,脂肪變性程度降低,正常肝細胞數目較未干預組有所恢復。肝和胰島組織BAX和BCL-2蛋白免疫組化結果表明,抗菌肽Dybowskin-2CDYa能上調BCL-2蛋白表達,下調BAX蛋白表達,從而抑制肝、胰島細胞凋亡,對肝和胰島起保護作用。
[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，

本文編號：1609474