胰腺纤维化进程中大鼠胰腺GnRH及GnRHR、Bcl-2及Bax、胰岛β细胞功能的变化  

Changes in GnRH,GnRHR,Bcl-2 and Bax in pancreas and the function of islet β cell in the procession of pancreatic fibrosis in rats

作　　者：叶晓莉[1] 付建芳[1] 曹宏伟[1] 王立会[1] 刘涛[1] 姬秋和[1] 

机构地区：[1]第四军医大学西京医院内分泌代谢科,西安710032

出　　处：《解放军医学杂志》2010年第8期923-928,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(30870948);陕西省自然科学基金(2009JQ4009)

摘　　要：目的观察SD大鼠胰腺纤维化进展过程中胰腺促性腺激素释放激素(GnRH)及其受体(GnRHR)、Bcl-2和BaxmRNA水平及胰岛β细胞功能的变化。方法 25只SD雄性大鼠随机均分为5组:正常组及注药1、2、3、6周组。注药组采用反复腹腔内注射二乙基二硫代氨基甲酸盐(DDC)法制作胰腺纤维化大鼠模型,剂量为500mg/kg,每周2次,正常组注射等量生理盐水。所有大鼠灌胃法行口服葡萄糖耐量试验(OGTT)测定血糖、血清胰岛素并计算空腹胰岛素与空腹血糖比值(FINS/FBG)、糖负荷30min时胰岛素与血糖比值[INS/PG(30min)]、糖负荷30min时胰岛素净增量与血糖净增量比值[ΔIRI/ΔBS(30min)]、血糖/胰岛素曲线下面积[GLU/(INS-AUC)]、稳态模型评估胰岛素抵抗(HOMA-IR)评价胰岛β细胞功能;光镜下观察胰腺病理改变;实时定量PCR法检测各组大鼠胰腺GnRH、GnRHR、Bcl-2及BaxmRNA表达水平。结果光镜下观察胰腺切片,注药1、2、3周组可见炎症细胞浸润、空泡变化、小叶间隙增宽,注药6周组可见腺泡细胞呈纤维素样排列。OGTT试验中各组间各时间点血糖无差异(P>0.05);与正常组比较,注药3周组空腹胰岛素(FINS)水平升高,注药2、6周组15min及60min胰岛素、注药2周组30min胰岛素、注药1、2、6周组120min胰岛素水平下降(P<0.05)。与正常组比较,注药3周组FINS/FBG和HOMA-IR明显升高,注药2周组FINS/FBG下降,注药2周组和注药6周组INS/PG(30min)、ΔIRI/ΔBS(30min)和INS-AUC下降(P<0.05)。与正常组比较,注药1、2、3周组胰腺GnRH表达均下降,注药6周组表达上升,注药组胰腺GnRHR表达均降低,胰腺Bcl-2和Bax表达均增加,Bcl-2∶Bax比值升高(P<0.05)。胰腺GnRH与FBG呈负相关(r=-0.443);胰腺GnRHR与糖负荷15min时血清胰岛素呈正相关(r=0.435),与Bcl-2∶Bax呈负相关(r=-0.813)。结论 GnRHR可能参与胰腺纤维化早期阶段的Bcl-2和Bax介导的细胞凋亡,导致早期胰岛β细胞功能下降,减少胰岛素分泌,Objective To study the expressions of gonadotropin-releasing hormone （GnRH）,its receptor （GnRHR）,Bcl-2 and Bax mRNA of pancreas and the changes in islet β cells function in the procession of pancreatic fibrosis in SD rats. Methods Twenty-five male SD rats were randomly and averagely divided into five groups：normal group and other four groups treated by repeated intraperitoneal injection with DDC （diethyldithiocarbamate） for 1,2,3 and 6 weeks respectively. DDC was administered in the dose of 500mg/kg,twice a week. Rats in normal group were treated with equal volume of normal saline. Oral glucose tolerance tests （OGTT） were performed after gavage of glucose and measurement of blood glucose and serum insulin concentration. FINS/FBG （fasting insulin to fasting blood glucose ratio）,30min INS/PG （30 minutes glucose post-load insulin to glucose ratio）,30min ΔIRI/ΔBS （30 minutes glucose post-load insulin increment to glucose increment ratio）,HOMA-IR （homeostasis model assessment-insulin resistance） and GLU/INS-AUC （glucose/insulin area under curve） were calculated to evaluate islet β cell function. Pathological changes of the pancreas were examined with optical microscopy. Real-time quantitative PCR （SYBR Green） was done to detect the expression of GnRH,GnRHR,Bcl-2 and Bax mRNA of pancreas. Results Microscopic examination of pancreatic specimens revealed that there were inflammatory cells infiltration,vacuolar change and widened lobular gap in groups treated with DDC for 1,2 and 3 weeks; acinar cells presented a cellulose-like arrangement in group treated with DDC for 6 weeks. OGTT showed no significant difference in blood glucose level between groups at same time points （P 0.05）. Compared with normal group,OGTT revealed that fasting serum insulin increased in group treated with DDC for 3 weeks,however,the serum insulin level declined （P0.05） at 15min and 60min in groups treated with DDC for 2 and 6 weeks,at 30min in group treated with DDC for 2 weeks,and at 120min in

关 键 词：胰腺纤维化 促性腺激素释放激素 受体 Β细胞功能 葡萄糖耐量试验 

分 类 号：R587.1[医药卫生—内分泌]