给予胰岛素样生长因子-I（IGF-I）的急性肾衰竭大鼠中的IGF-I结合蛋白、IGF-I结合蛋白mRNA和IGF-I受体mRNA

IGF-I binding proteins, IGF-I binding protein mRNA and IGF-I receptor mRNA in rats with acute renal failure given IGF-I.

作者信息

Bohé J, Ding H, Qing D P, Yoon K, Hirschberg R, Wolfgang G H, Kopple J D

机构信息

Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, California 90509, USA.

出版信息

Kidney Int. 1998 Oct;54(4):1070-82. doi: 10.1046/j.1523-1755.1998.00096.x.

DOI:10.1046/j.1523-1755.1998.00096.x

PMID:9767523

Abstract

BACKGROUND

Recombinant human insulin-like growth factor-I (rhIGF-I) accelerates recovery from acute renal failure (ARF) in rats. IGF-I acts through the IGF-I receptor (IGF-IR) and its actions may be modified by IGF-I binding proteins (IGFBPs). It therefore would be of value to determine the effects of both ARF and rhIGF-I treatment on serum IGFBPs and mRNA for IGFBPs and IGF-IR.

METHODS

Rats with ARF and sham-operated control rats were randomized to receive rhIGF-I or vehicle injections thrice daily for 72 to 74 hours starting five hours after surgery. Serum IGFPBs 1 to 6 were measured serially, and mRNA for IGFBPs 1 to 6 and for IGF-IR were measured in several tissues obtained 72 to 74 hours after surgery.

RESULTS

At 72 to 74 hours, serum IGFBP-1 and IGFBP-2 levels were higher in rhIGF-I treated rats. Serum IGFBP-3 was affected by both ARF and rhIGF-I. IGFBP-4 rose transiently only in ARF groups. At 72 to 74 hours, mRNA for several IGFBPs was reduced in renal cortex of ARF rats. Low mRNA for IGFBP-4 and -6 was observed in renal medulla of the ARF rats, particularly in comparison to the sham-operated rats receiving vehicle. Renal medullary IGFBP-2 mRNA was decreased in ARF and sham rats given rhIGF-I as compared to sham animals given vehicle. Hepatic IGFBP-2 mRNA was higher in both rhIGF-I treated groups versus those given vehicle. Otherwise, there were no differences in IGFBP mRNAs among the four groups in lung, heart, and skeletal muscle. IGF-IR mRNA was decreased in renal cortex and medulla of both ARF groups and was not detected in liver in any group.

CONCLUSIONS

Thus, ARF and rhIGF-I treatment each affected certain serum IGFBPs and jointly affected some IGFBPs. ARF suppressed gene transcription for renal cortical and medullary IGF-IR and some IGFBPs. rhIGF-I independently affected some renal cortical or medullary IGFBP mRNAs. rhIGF-I increased hepatic IGFBP-2 mRNA and serum IGFBP-2. These effects of ARF or rhIGF-I may influence rhIGF-I actions in rats with ischemic ARF.

摘要

背景

重组人胰岛素样生长因子-I（rhIGF-I）可加速大鼠急性肾衰竭（ARF）的恢复。IGF-I通过IGF-I受体（IGF-IR）发挥作用，其作用可能会被IGF-I结合蛋白（IGFBPs）改变。因此，确定ARF和rhIGF-I治疗对血清IGFBPs以及IGFBPs和IGF-IR mRNA的影响具有重要意义。

方法

将ARF大鼠和假手术对照大鼠随机分组，自手术后5小时起，每日三次注射rhIGF-I或赋形剂，持续72至74小时。连续测定血清IGFPB 1至6，并在手术后72至74小时获取的多个组织中测定IGFBPs 1至6和IGF-IR的mRNA。

结果

在72至74小时时，rhIGF-I治疗组大鼠的血清IGFBP-1和IGFBP-2水平较高。血清IGFBP-3受ARF和rhIGF-I两者影响。IGFBP-4仅在ARF组中短暂升高。在72至74小时时，ARF大鼠肾皮质中几种IGFBPs的mRNA减少。在ARF大鼠的肾髓质中观察到IGFBP-4和-6的mRNA水平较低，特别是与接受赋形剂的假手术大鼠相比。与接受赋形剂的假手术动物相比，给予rhIGF-I的ARF和假手术大鼠肾髓质中的IGFBP-2 mRNA减少。在两个rhIGF-I治疗组中，肝脏IGFBP-2 mRNA均高于给予赋形剂的组。此外，在肺、心脏和骨骼肌的四组中，IGFBP mRNA没有差异。在两个ARF组的肾皮质和髓质中，IGF-IR mRNA均减少，且在任何组的肝脏中均未检测到。

结论

因此，ARF和rhIGF-I治疗各自影响某些血清IGFBPs，并共同影响一些IGFBPs。ARF抑制肾皮质和髓质IGF-IR以及一些IGFBPs的基因转录。rhIGF-I独立影响一些肾皮质或髓质IGFBP mRNA。rhIGF-I增加肝脏IGFBP-2 mRNA和血清IGFBP-2。ARF或rhIGF-I的这些作用可能会影响缺血性ARF大鼠中rhIGF-I的作用。