本文選題：他克莫司(FK506)　切入點：空腹血糖(FPG)　出處：《南昌大學》2015年碩士論文　論文類型：學位論文

【摘要】：目的:探討他克莫司(Tacrolimus,FK506)對大鼠胰島β細胞分泌胰島素功能的影響及了解FK506對血清GLP-1濃度的影響。方法:1、將SD大鼠采用不同濃度的FK506灌胃,FK506濃度分為H組2mg/(kg·d),M組1mg/(kg·d),L組0.5mg/(kg·d),以生理鹽水灌胃為對照組(C組),每3天測量體質量,每日禁食約10小時灌胃,灌胃后1h進食,禁食期間不禁水。2、FK506灌胃前以及灌胃后每月采用葡萄糖氧化酶法測定大鼠空腹血漿葡萄糖(FPG)。3、FK506灌胃1月后及4月后采用酶聯(lián)免疫(ELISA)法測定空腹血清胰島素水平(FINS);FK506灌胃4月后采用酶聯(lián)免疫(ELISA)法測定血清胰高血糖素樣肽-1(GLP-1)水平。4、根據(jù)空腹血糖及空腹胰島素計算出胰島素分泌指數(shù)(HOMA-β)及胰島素抵抗指數(shù)(HOMA-IR)。5、HE染色觀察胰島組織學結構變化。6、比較不同階段不同濃度FK506灌胃后大鼠體質量、FPG、FINS、HOMA-β、HOMA-IR、GLP-1的水平以及胰腺組織學結構變化。結果:1、FK506灌胃1月后,各組大鼠體質量增長值、FPG、FINS、HOMA-β、HOMA-IR均無明顯變化(P0.05)。2、FK506灌胃1月后,各組胰腺HE染色均為胰島結構清晰,形態(tài)完整。3、FK506灌胃4月后,各組間體質量增長值隨FK506濃度的增加而減少,其中H組及M組顯著低于L組及C組(P0.01),L組與C組間無明顯差異(P0.05)。4、FK506灌胃4月后,各實驗組大鼠FPG較C組均明顯升高,以H組最為明顯,血糖升高幅度與FK506濃度呈正相關。5、FK506灌胃4月后,各實驗組大鼠FINS、HOMA-β水平均有下降,與FK506濃度呈負相關。6、FK506灌胃4月后,各實驗組大鼠HOMA-IR水平均有升高,與FK506濃度呈正相關。7、FK506灌胃4月后,各組大鼠GLP-1的表達無明顯統(tǒng)計學意義(P0.05)。8、FK506灌胃4月后,與C組相比,H、M兩組大鼠胰腺導管均遭到不同程度破壞,胰島細胞數(shù)量減,出現(xiàn)空泡樣變,L組組織學改變不明顯。結論:FK506灌胃后大鼠可出現(xiàn)多飲多尿的臨床癥狀,FK506短期使用不會造成血糖、胰島β細胞功能的變化,后期逐漸導致血糖升高,胰島素分泌減少,胰島素分泌指數(shù)減少,抵抗指數(shù)增加,胰腺組織空泡變性且這些改變與FK506濃度密切相關。
[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.
【學位授予單位】：南昌大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R587.1

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本文編號：1644961