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糖尿病大鼠使用艾考糊精透析时腹膜晚期糖基化终产物的蓄积

Peritoneal accumulation of advanced glycosylation end-products in diabetic rats on dialysis with icodextrin.

作者信息

Lee J H, Reddy D K, Saran R, Moore H L, Twardowski Z J, Nolph K D, Khanna R

机构信息

Division of Nephrology, Dongguk University Medical Center, Kyongju, Korea.

出版信息

Perit Dial Int. 2000;20 Suppl 5:S39-47.

Abstract

OBJECTIVE

To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and formation of advanced glycosylation end-products (AGEs) in the peritoneal membrane in the diabetic rat model of peritoneal dialysis (PD).

STUDY DESIGN

Thirty-three male Sprague-Dawley rats weighing between 275 - 300 g were divided into 5 groups: group C (n = 6), control rats with catheter but not dialyzed; group D (n = 5), diabetic rats with catheter but not dialyzed; group G (n = 7), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for the overnight exchange; group H (n = 8), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were performed three times daily with an instillation volume of 25 mL per exchange for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics.

RESULTS

The level of immunostaining was lowest in group C and highest in group G. Significant differences were seen between group C and groups G, H, and I (p < 0.001, p = 0.001, and p< 0.05 respectively). Significant differences were also found between group G and groups D and I (p < 0.05 and p < 0.05 respectively). Over time, glucose concentration at the end of an exchange versus concentration at instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea increased. Significant differences were found between groups C and H for D/D0 glucose (0.40+/-0.01 vs 0.35+/-0.01, p < 0.05); and between groups C and H for D/P urea (0.87+/-0.03 vs 0.97+/-0.02, p < 0.05).

CONCLUSIONS

These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solutions. We conclude that the use of icodextrin may be helpful in slowing the deterioration of the peritoneal membrane, prolonging its use for dialysis.

摘要

目的

在糖尿病大鼠腹膜透析(PD)模型中,评估并比较基于葡萄糖的溶液与艾考糊精对腹膜转运特性及腹膜中晚期糖基化终产物(AGEs)形成的影响。

研究设计

33只体重在275 - 300克之间的雄性Sprague-Dawley大鼠被分为5组:C组(n = 6),有导管但未进行透析的对照大鼠;D组(n = 5),有导管但未进行透析的糖尿病大鼠;G组(n = 7),白天用标准2.5%葡萄糖溶液进行交换、夜间用4.25%葡萄糖溶液进行交换的糖尿病大鼠;H组(n = 8),白天用标准2.5%葡萄糖溶液进行交换、夜间用7.5%艾考糊精溶液进行交换的糖尿病大鼠;I组(n = 7),所有交换均使用7.5%艾考糊精溶液的糖尿病大鼠。每天进行3次透析交换,每次注入量为25毫升,持续12周。组织切片用单克隆抗AGE抗体染色。每4周进行一次1小时腹膜平衡试验(PET)以比较转运特性。

结果

免疫染色水平在C组最低,在G组最高。C组与G组、H组和I组之间存在显著差异(分别为p < 0.001、p = 0.001和p < 0.05)。G组与D组和I组之间也发现了显著差异(分别为p < 0.05和p < 0.05)。随着时间推移,交换结束时的葡萄糖浓度与注入时的浓度之比(D/D0葡萄糖)降低,尿素的透析液与血浆之比(D/P)增加。C组和H组在D/D0葡萄糖方面存在显著差异(0.40±0.01对0.35±0.01,p < 0.05);C组和H组在D/P尿素方面也存在显著差异(0.87±0.03对0.97±0.02,p < 0.05)。

结论

这些结果表明,使用含艾考糊精的腹膜透析液比使用基于葡萄糖的溶液时AGE形成更低。我们得出结论,使用艾考糊精可能有助于减缓腹膜的恶化,延长其用于透析的时间。

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