摘要
β细胞素(betacellulin,BTC)是目前较受关注的胰岛再生因子,但其促胰腺、胰岛再生的机制不清.BTCe是betacellulin的功能片段,促细胞增殖能力与BTC相同.实验通过原核表达方法获得BTCe蛋白,MTT法证实其促3T3-L1细胞增殖能力.将BTC或BTCe作用于原代培养的大鼠胰岛,观察其对胰岛分泌的急性及长期影响作用,实时定量PCR及免疫荧光检测胰岛内关键基因的表达.将质粒pcDNA3.1-BTCe注射入链脲霉素(STZ)诱导的糖尿病大鼠肌肉中,观察对大鼠血糖的影响作用.加入BTC或BTCe可明显提高体外培养大鼠胰岛的GSIS水平,但实时定量PCR及免疫荧光显示胰岛内4种关键基因的表达并无明显变化;pcDNA3.1-BTCe转染糖尿病大鼠15～20天后血糖出现下降,糖耐量明显改善;免疫荧光显示:胰腺内有大量PDX-1+的导管细胞及胰岛素阳性细胞出现.推测BTC及BTCe对体外长期培养的大鼠胰岛具有一定的保护作用,可能通过促进胰腺内PDX-1+的导管细胞及胰岛素阳性细胞的增殖、诱导对STZ诱导的糖尿病大鼠的高血糖具有一定缓解作用.
Betacellulin （BTC） is one of ＂islets regeneration factors＂ which received more and more attention these years. BTCe is the C-terminal 50-residue region of mature BTC protein and can bind with erbB-1, erbB-4 receptor. It has the same mitogenic activity on cells as the whole section. BTC and BTCe can improve the level of glucose-stimulated insulin secretion （GSIS） during islets culture in vitro though they had no effect on the acute insulin secretion. BTCe also effectively ameliorated the hyperglycemia of STZ-induced diabetic rats by a single plasmid injection into muscle of rats. It is supposed that BTCe promote the proliferation of PDX-1 positive cells or repair some signal transduction pathway. Perhaps the latter is more important.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2006年第12期1190-1199,共10页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目(30470817)
上海市科委重大项目(04DZ19507)
同济大学优秀青年培养基金
上海市第十人民医院启明星基金资助~~
