重组人表皮生长因子对中毒性急性肾小管坏死恢复的促进作用

Recombinant human epidermal growth factor accelerates the recovery of the toxic acute tubular necrosis

目的:探讨国产重组人表皮生长因子(recombinant human epidermal growth factor,rhEGF)对庆大霉素(gentamicin,GM)中毒性急性肾小管坏死的恢复是否具有促进作用并探讨其机制。方法:将成年Wistar大鼠随机分成3组。GM组,GM皮下注射2 d,400 mg/(kg.d);EGF组,按上法注射GM,于最后1次注射GM后2 h开始rhEGF皮下注射3 d,90μg/d;对照组,注射等量生理盐水代替GM。分别于首次注射GM后第2,5,8,11,15,22和29天处死各组大鼠并观察肾功能指标及肾脏组织形态学的改变,包括HE,PAS染色分级,并用免疫组织化学的方法检测肾脏组织中热休克蛋白27(heat shock protein 27,HSP27)的表达。结果:GM注射大鼠肾功能明显受损,但EGF组肾功能损伤程度较GM组轻,并提前恢复正常。组织学分级比较显示,第11和15天EGF组明显好于GM组。免疫组织化学结果显示,EGF组HSP27的表达强于GM组。结论:国产rhEGF具有促进GM中毒性急性肾小管坏死形态和功能恢复的作用,这可能与其促进小分子量热休克蛋白的表达有关。

Objective To study whether the domestic recombinant human epidermal growth factor （rhEGF） accelerates the recovery of gentamicin （GM）-induced toxic acute tubular necrosis in rats. Methods Mature Wistar rats were randomly divided into 3 groups. GM group given subcutaneous injection of GM[400 mg/（ kg · d） ] for 2 days; EGF group given GM injection as GM group and given subcu- taneous injection of rhEGF （90μ g/d） 2 h after the last GM injection for 3 days ; Control group given the same amount of normal saline instead of GM. At day 2, 5, 8, 11 , 15, 22, and 29 after the first injection of GM, the rats of 3 groups were killed. Renal function index, renal histological grading by HE and PAS staining, and the immunohistochemical expression of HSP27 in the kidneys were observed. Results After GM injection, the kidney functions were obviously damaged in both GM group and EGF group. But EGF group was not so serious as GM group and returned to normal levels earlier than GM group. Renal histological grading comparison indicated the difference of damage between the EGF and GM groups was significant at day 11 and 15, and the kidneys of EGF group were obviously improved compared with those of GM group, lmnmnohistochemically, the expression of HSP27 in EGF group rats was much more obvious than that of GM group rats. Conclusion The domestic rhEGF is effective in accelerating the morphological and functional recovery of GM-induced acute tubular necrosis in rats, which may be related with the high expression of small HSP.