FK506对大鼠胰岛β细胞功能的影响

发布时间：2018-03-21 18:05

本文选题：他克莫司(FK506)　切入点：空腹血糖(FPG)　出处：《南昌大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:探讨他克莫司(Tacrolimus,FK506)对大鼠胰岛β细胞分泌胰岛素功能的影响及了解FK506对血清GLP-1浓度的影响。方法:1、将SD大鼠采用不同浓度的FK506灌胃,FK506浓度分为H组2mg/(kg·d),M组1mg/(kg·d),L组0.5mg/(kg·d),以生理盐水灌胃为对照组(C组),每3天测量体质量,每日禁食约10小时灌胃,灌胃后1h进食,禁食期间不禁水。2、FK506灌胃前以及灌胃后每月采用葡萄糖氧化酶法测定大鼠空腹血浆葡萄糖(FPG)。3、FK506灌胃1月后及4月后采用酶联免疫(ELISA)法测定空腹血清胰岛素水平(FINS);FK506灌胃4月后采用酶联免疫(ELISA)法测定血清胰高血糖素样肽-1(GLP-1)水平。4、根据空腹血糖及空腹胰岛素计算出胰岛素分泌指数(HOMA-β)及胰岛素抵抗指数(HOMA-IR)。5、HE染色观察胰岛组织学结构变化。6、比较不同阶段不同浓度FK506灌胃后大鼠体质量、FPG、FINS、HOMA-β、HOMA-IR、GLP-1的水平以及胰腺组织学结构变化。结果:1、FK506灌胃1月后,各组大鼠体质量增长值、FPG、FINS、HOMA-β、HOMA-IR均无明显变化(P0.05)。2、FK506灌胃1月后,各组胰腺HE染色均为胰岛结构清晰,形态完整。3、FK506灌胃4月后,各组间体质量增长值随FK506浓度的增加而减少,其中H组及M组显著低于L组及C组(P0.01),L组与C组间无明显差异(P0.05)。4、FK506灌胃4月后,各实验组大鼠FPG较C组均明显升高,以H组最为明显,血糖升高幅度与FK506浓度呈正相关。5、FK506灌胃4月后,各实验组大鼠FINS、HOMA-β水平均有下降,与FK506浓度呈负相关。6、FK506灌胃4月后,各实验组大鼠HOMA-IR水平均有升高,与FK506浓度呈正相关。7、FK506灌胃4月后,各组大鼠GLP-1的表达无明显统计学意义(P0.05)。8、FK506灌胃4月后,与C组相比,H、M两组大鼠胰腺导管均遭到不同程度破坏,胰岛细胞数量减,出现空泡样变,L组组织学改变不明显。结论:FK506灌胃后大鼠可出现多饮多尿的临床症状,FK506短期使用不会造成血糖、胰岛β细胞功能的变化,后期逐渐导致血糖升高,胰岛素分泌减少,胰岛素分泌指数减少,抵抗指数增加,胰腺组织空泡变性且这些改变与FK506浓度密切相关。
[Abstract]:Objective: to investigate the effect of tacrolimus on insulin secretion by islet 尾 cells in rats and to understand the effect of FK506 on serum GLP-1 concentration. The body mass was measured every 3 days in group C (control group) by intragastric administration of normal saline. Fasting for about 10 hours daily, feeding at 1 hour after feeding. Determination of fasting Serum Insulin level of FK506 before and after fasting by glucose Oxidase method in Rat fasting Plasma FPGN. 3FK506 after gastric instillation for 1 month and 4 months later, fasting Serum Insulin level and FK506 FK506 were measured by enzyme linked immunosorbent Assay (ELISAs) method and FK506 / FK506 / FK506 / FK506 / FK506 / FK506 / FK506 / FK506 / FK506 / FK506. After April, serum glucagon like peptide-1 (GLP-1) was determined by enzyme linked immunosorbent assay (Elisa). The insulin secretion index (HOMA- 尾) and insulin resistance index (HOMA- 尾) were calculated according to fasting blood glucose and fasting insulin. The histological structure of islets was observed by HE staining. 6, compare the level of GLP-1 and the histological structure of pancreas in rats with different concentrations of FK506 at different stages after intragastric administration of FINS- 尾 -HOMA- 尾 HOMA- 尾 Homa. Results one month after 1 month of gastric perfusion of FK506, FK506 was perfused with different concentrations of FK506. There was no significant change in body mass growth value and HOMA- 尾 -IR of each group. After January, the pancreatic HE staining of each group was characterized by clear pancreatic islet structure, morphological integrity. 3FK506 was perfused to stomach on April, and the increase value of body mass in each group decreased with the increase of FK506 concentration. Group H and group M were significantly lower than those in group L and group C (P 0.01). There was no significant difference between group C and group C. The FPG in each experimental group was significantly higher than that in group C, especially in group H. There was a positive correlation between the increase of blood glucose and the concentration of FK506 on April, the level of HOMA- 尾 in FINSX decreased in all experimental groups, but negatively correlated with the concentration of FK506. The level of HOMA-IR in each experimental group was increased after the gastric administration of FK506 on April, and there was no significant difference between FK506 and FK506 in each experimental group. There was no significant difference in the expression of GLP-1 in rats of each group after 4 months of intragastric administration of FK506. There was no significant difference in the expression of GLP-1. Compared with group C, the pancreatic ducts were damaged and the number of islet cells was decreased in both groups. There were no obvious histological changes in group L with vacuolar degeneration. Conclusion the clinical symptoms of polydipsy and polyuria can be found in the rats after oral administration of FK506. FK506 does not cause changes in blood glucose, 尾 -cell function of pancreatic islets, and gradually increase blood glucose in the later stage of administration of FK506. The decrease of insulin secretion, the decrease of insulin secretion index, the increase of resistance index, and the vacuolar degeneration of pancreatic tissue were closely related to the concentration of FK506.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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