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罗格列酮通过抑制链脲佐菌素诱导的糖尿病大鼠肾细胞间黏附分子-1表达发挥肾脏保护作用。

Renoprotective effect of rosiglitazone through the suppression of renal intercellular adhesion molecule-1 expression in streptozotocin-induced diabetic rats.

作者信息

Qian Y, Li S, Ye S, Chen Y, Zhai Z, Chen K, Yang G

机构信息

Department of Endocrinology, Anhui Provincial Hospital, Hefei, China.

出版信息

J Endocrinol Invest. 2008 Dec;31(12):1069-74. doi: 10.1007/BF03345654.

DOI:10.1007/BF03345654
PMID:19246972
Abstract

OBJECTIVE

To observe the effect of rosiglitazone on serum intercellular adhesion molecule-1 (SICAM-1) level, urinary excretion of ICAM-1, and renal expression of ICAM-1, and investigate its possible renoprotective mechanisms in diabetic rats.

METHOD

Twenty-four Wistar Rats were divided into 3 groups: non-diabetic control rats (group A, no.=8), streptozotocin-induced diabetic rats (group B, no.=8), and diabetic rats treated with rosiglitazone (group C, no.=8). Rats in group C were treated with rosiglitazone (5 mg x kg(-1) x d(-1)) 1 week after the establishment of diabetic model, group A and B were treated with corresponding sodium chloride. Peripheral blood glucose was tested weekly. Glycosylated hemoglobin (HbA1c) and SICAM-1 as well as urinary albumin excretion rate (UAER), urinary retinol binding-protein (URBP) excretion rate, and urinary ICAM-1 (UICAM- 1) excretion rate were tested at the 8th week, and the renal tissues of all rats were obtained for evaluating kidney/body weight ratio, observing pathologic change via electron microscope, and for examining the expression of ICAM-1 mRNA by reverse transcriptase-PCR.

RESULTS

At the 8th week, the blood glucose, HbA1c levels, UAER, URBP excretion rate, kidney/body weight ratio and serum, urinary ICAM-1 levels all increased significantly in group B and group C in comparison with group A; however, the above-mentioned parameters in group C (except the blood glucose and HbA1c levels) were much lower than those in group B. In addition, both SICAM-1 and UICAM-1 were highly correlated with the UAER, URBP level, and kidney/body weight ratio in all rats; renal pathological lesions observed by electron microscope in group C were much lighter than those of group B; compared with group A, the expression of ICAM-1 mRNA was markedly up-regulated in group B and group C, and rosiglitazone was able to decrease the expression of ICAM-1 mRNA in the renal tissue.

CONCLUSION

Rosiglitazone could definitely protect against the renal injury of diabetic rats, which may be partly associated with decreasing the expression of ICAM-1 in the renal tissue, reducing ICAM-1 productions in both serum and urine.

摘要

目的

观察罗格列酮对糖尿病大鼠血清细胞间黏附分子-1(SICAM-1)水平、ICAM-1尿排泄量及肾脏ICAM-1表达的影响,并探讨其可能的肾脏保护机制。

方法

将24只Wistar大鼠分为3组:非糖尿病对照大鼠(A组,n = 8)、链脲佐菌素诱导的糖尿病大鼠(B组,n = 8)和罗格列酮治疗的糖尿病大鼠(C组,n = 8)。C组大鼠在糖尿病模型建立1周后用罗格列酮(5 mg·kg⁻¹·d⁻¹)治疗,A组和B组用相应的氯化钠治疗。每周检测外周血糖。在第8周检测糖化血红蛋白(HbA1c)和SICAM-1以及尿白蛋白排泄率(UAER)、尿视黄醇结合蛋白(URBP)排泄率和尿ICAM-1(UICAM-1)排泄率,获取所有大鼠的肾脏组织以评估肾重/体重比,通过电子显微镜观察病理变化,并通过逆转录聚合酶链反应检测ICAM-1 mRNA的表达。

结果

在第8周时,与A组相比,B组和C组的血糖、HbA1c水平、UAER、URBP排泄率、肾重/体重比以及血清和尿ICAM-1水平均显著升高;然而,C组的上述参数(血糖和HbA1c水平除外)远低于B组。此外,在所有大鼠中,SICAM-1和UICAM-1均与UAER、URBP水平及肾重/体重比高度相关;C组电子显微镜观察到的肾脏病理损伤比B组轻得多;与A组相比,B组和C组ICAM-1 mRNA的表达明显上调,而罗格列酮能够降低肾脏组织中ICAM-1 mRNA的表达。

结论

罗格列酮确实可以预防糖尿病大鼠的肾脏损伤,这可能部分与降低肾脏组织中ICAM-1的表达、减少血清和尿液中ICAM-1的生成有关。

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