ROUX-EN-Y胃空肠旁路术对非肥胖型糖尿病小鼠血糖和胰岛祖细胞增殖分化的影响及其意义
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摘要
本实验旨在研究胃旁路术(RYGBPS)对链脲霉菌素(streptozotocin,STZ)所致非肥胖型糖尿病小鼠模型血糖的影响,及在该过程中胰岛祖细胞所发生的变化。探讨血糖变化和胰岛祖细胞变化以及体重变化等的相互关系。
方法
成年雄性C57BL/6小鼠经腹腔注射STZ(200mg/kg),建立非肥胖型糖尿病模型。成模后小鼠40只随机分为3组:GBP手术组(DMOP组)16只、假手术组(DMFOP组)16只、未处理组(DM组)8只,另设立正常对照组3组:正常未手术组(N组)8只、正常假手术组(NFOP组)8只和正常手术组(NOP)8只。DMOP组及DMFOP组内小鼠手术时间是STZ注射后第十天。分别测术前,术后第1、2、3、4、5、6周同一时间点各组实验动物的随机血糖及体重,同时监测饮水及尿量的变化。分别取术后第1、2、3、4周DMOP组中血糖下降明显及不明显的小鼠各一只,及于术后第4周随机抽取DM组、DMFOP组、N组,NOP组、NFOP组中小鼠一只,处死后取胰腺组织,通过HE染色和免疫荧光,观察组织学变化。
结果
(1)与DM、DMFOP组相比,DMOP组的小鼠血糖下降明显,并可以维持到术后6周以上(实验观察结束)。(2)GBP手术后,糖尿病小鼠的体重回升,多饮、多尿的症状好转。(3)DMFOP组(15/16)与DMOP组(2/16)比较,小鼠围手术期死亡率差异明显(p＜0.01)。(4)HE染色发现:与对照组小鼠相比,术后第四周的DMOP组小鼠胰岛形态接近正常胰岛,并出现新生的小胰岛,多分布在胰腺导管周围。(5)免疫荧光染色显示:胰岛数目增加,胰岛素免疫荧光发现较多孤立的及由两三个胰岛素阳性细胞组成的小胰岛。胰岛素和胰高血糖素免疫荧光双标发现在部分胰岛内存在胰岛素和胰高血糖素双阳性(INS+/GLU+)的细胞,目前,胰岛素和胰高血糖素双阳性细胞被认为是未成熟型内分泌前体细胞。同时,免疫荧光染色还发现胰腺组织内散在的表达Ngn3的细胞。Ngn3是内分泌祖细胞表达的标记物之一。
结论
1.GBP手术对糖尿病小鼠具有降血糖作用。
2.GBP手术可以促进胰岛再生。
Objective
To investigate the effect of Roux-en-y gastric bypass on blood glucose in STZ (streptozotocin) induced diabetic mice,the changes of pancreatic progenitor cell in this progress.To explore the relationship between declination of blood glucose and variation of pancreatic progenitor cell and the relationship between declination of blood glucose and changed body mass.
Methods
We produce a none obese diabetic model on mature C57BL/6 mice by peritoneal injection of STZ(200mg/kg),40 diabetic mice were allocated into three groups randomly:16 in GBP group(DMOP),16 in shame operation group(DMFOP) and 8 in untreated control group(DM).On the same time,3 normal mice control groups were set:8 for GBP group(NOP),8 in shame operation group(NFOP) and 8 for untreated group(N).Operations were performed on the mice of DMOP and DMFOP groups ten days after injection of STZ.Blood glucose were measured on all mice before and 1 week,2 weeks,3weeks,4weeks,5weeks,6weeks after operation and body weight were measured simultaneously.Hypoglycaemia and hyperglycaemia mice were picked out from DMOP group on 1st,2nd,3rd and 4th week after the process,on the other hand,one of mice were selected from each group of DMFOP,DM,N,NFOP and NOP on the 4th week randomly.They were all sacrificed to characterize the pancreatic morphological changes.We performed immunohistochemical and HE analysis on the tissue sections.
Results 1.Comparing with preoperation and DM or DMFOP control group,random blood glucose of mice were reduce significantly post operation.The declination of blood sugar sustained more than 6 weeks after operations(till the end of experimental investigations).2.Perioperative mortality was different between DMOP(2/16) and DMFOP(15/16) group.3.HE staining showed that,in the DMOP group,insular morphous were similar to normal on 4th week post operation.At the same time,we found many newly small islets around pancreatic ducts and some of them consist of only one,two or three insulin positive cells.4.Discovery from immunofluorescence staining:by simultaneous insulin and glucagon cell detection,(GLU+/INS+) double expression cell could be found in some islets,so far,coexpression of insulin and glucagon were regarded as a index of premature endocrine precursor cell.Ngn3 positive cells dispersed in the pancreas were dectected.Ngn3 is one of markers from endocrine progenitor cell.
Conclusion
1.GBP can markedly reduce plasma glucose in diabetic mice.
2.GBP can promote the regeneration of islets of pancreas.
方法
成年雄性C57BL/6小鼠经腹腔注射STZ(200mg/kg),建立非肥胖型糖尿病模型。成模后小鼠40只随机分为3组:GBP手术组(DMOP组)16只、假手术组(DMFOP组)16只、未处理组(DM组)8只,另设立正常对照组3组:正常未手术组(N组)8只、正常假手术组(NFOP组)8只和正常手术组(NOP)8只。DMOP组及DMFOP组内小鼠手术时间是STZ注射后第十天。分别测术前,术后第1、2、3、4、5、6周同一时间点各组实验动物的随机血糖及体重,同时监测饮水及尿量的变化。分别取术后第1、2、3、4周DMOP组中血糖下降明显及不明显的小鼠各一只,及于术后第4周随机抽取DM组、DMFOP组、N组,NOP组、NFOP组中小鼠一只,处死后取胰腺组织,通过HE染色和免疫荧光,观察组织学变化。
结果
(1)与DM、DMFOP组相比,DMOP组的小鼠血糖下降明显,并可以维持到术后6周以上(实验观察结束)。(2)GBP手术后,糖尿病小鼠的体重回升,多饮、多尿的症状好转。(3)DMFOP组(15/16)与DMOP组(2/16)比较,小鼠围手术期死亡率差异明显(p＜0.01)。(4)HE染色发现:与对照组小鼠相比,术后第四周的DMOP组小鼠胰岛形态接近正常胰岛,并出现新生的小胰岛,多分布在胰腺导管周围。(5)免疫荧光染色显示:胰岛数目增加,胰岛素免疫荧光发现较多孤立的及由两三个胰岛素阳性细胞组成的小胰岛。胰岛素和胰高血糖素免疫荧光双标发现在部分胰岛内存在胰岛素和胰高血糖素双阳性(INS+/GLU+)的细胞,目前,胰岛素和胰高血糖素双阳性细胞被认为是未成熟型内分泌前体细胞。同时,免疫荧光染色还发现胰腺组织内散在的表达Ngn3的细胞。Ngn3是内分泌祖细胞表达的标记物之一。
结论
1.GBP手术对糖尿病小鼠具有降血糖作用。
2.GBP手术可以促进胰岛再生。
Objective
To investigate the effect of Roux-en-y gastric bypass on blood glucose in STZ (streptozotocin) induced diabetic mice,the changes of pancreatic progenitor cell in this progress.To explore the relationship between declination of blood glucose and variation of pancreatic progenitor cell and the relationship between declination of blood glucose and changed body mass.
Methods
We produce a none obese diabetic model on mature C57BL/6 mice by peritoneal injection of STZ(200mg/kg),40 diabetic mice were allocated into three groups randomly:16 in GBP group(DMOP),16 in shame operation group(DMFOP) and 8 in untreated control group(DM).On the same time,3 normal mice control groups were set:8 for GBP group(NOP),8 in shame operation group(NFOP) and 8 for untreated group(N).Operations were performed on the mice of DMOP and DMFOP groups ten days after injection of STZ.Blood glucose were measured on all mice before and 1 week,2 weeks,3weeks,4weeks,5weeks,6weeks after operation and body weight were measured simultaneously.Hypoglycaemia and hyperglycaemia mice were picked out from DMOP group on 1st,2nd,3rd and 4th week after the process,on the other hand,one of mice were selected from each group of DMFOP,DM,N,NFOP and NOP on the 4th week randomly.They were all sacrificed to characterize the pancreatic morphological changes.We performed immunohistochemical and HE analysis on the tissue sections.
Results 1.Comparing with preoperation and DM or DMFOP control group,random blood glucose of mice were reduce significantly post operation.The declination of blood sugar sustained more than 6 weeks after operations(till the end of experimental investigations).2.Perioperative mortality was different between DMOP(2/16) and DMFOP(15/16) group.3.HE staining showed that,in the DMOP group,insular morphous were similar to normal on 4th week post operation.At the same time,we found many newly small islets around pancreatic ducts and some of them consist of only one,two or three insulin positive cells.4.Discovery from immunofluorescence staining:by simultaneous insulin and glucagon cell detection,(GLU+/INS+) double expression cell could be found in some islets,so far,coexpression of insulin and glucagon were regarded as a index of premature endocrine precursor cell.Ngn3 positive cells dispersed in the pancreas were dectected.Ngn3 is one of markers from endocrine progenitor cell.
Conclusion
1.GBP can markedly reduce plasma glucose in diabetic mice.
2.GBP can promote the regeneration of islets of pancreas.
引文
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