Recombinant Human Epidermal Growth Factor Accelerates The Recovery Of The Toxic Acute Tubular Necrosis

Objective To study whether the domestic recombinant human Epidermal Growth Factor(rhEGF) accelerates the recovery of gcntamicin(GM)-induced toxic acute tubular necrosis in rats and the possible mechanism.Methods 3 groups of mature Wistar rats were applied: group 1(GM group), given subcutaneous injection of G\l(400mg/Kg/day) for 2 days; group 2(EGF group), given GM injection as GM group and given subcutaneous injection of rhEGF(90|ig/day) 2 hours after the last GM injection for 3 days; group 3(control group), given the same amount of normal saline instead of GM. At days 2, 5. 8, 11, 15, 22, and 29 after the first injection of GM, the rats of 3 groups were killed 6 hours after given peritoneal injection of BrdU and the followings were observed: 1. Renal function indices including urine voIume(UV). urine protein(UP), serum creatinine(SCr), blood urea nitrogcn(BUN), crcatinine clearancc(CCr). natrium excretion fraction(FE\a) and urine EGF(by radioimmunoassax); 2. Renal histomorphological changes including histological grading(0-3) by HE and PAS stain and the immunohistochemical expression of Bcl-2, BrdU and HSP27 in the kidneys.Results UV, UP, SCr, BUN levels and FEXa increased after GM injection both in GM group and EGF group. There was no significant difference between UV levels of the two groups. The UP, SCr and BUN levels of EGF group were significantly lower than those of GM group. The FEya and CCr of EGF group went back to normal 7 daysearlier than those of GM group. Urine EGF levels of the 2 groups decreased after the damage and then increased during the recovery course, but EGF group returned to normal levels 7 days earlier than GM group. Renal histological grading comparison indicated the difference of damage between the 2 groups \vas not significant at days 2 and 5 after the first injection, but significant at days 11 and 1 5, and the kidneys of EGF group were obviously improved compared with those of GV1 group. Immunohislochemically, the expression of Bcl-2 and HSP27 in EGF group rats was much more obvious than that of GM group rats. The expression of BrdU in EGF group reached its peak 3 days earlier than that in GM group.Conclusion 1 .The domestic rhEGF is effective in accelerating the morphological and functional recovery of gentamicin-induced acute tubular necrosis in rats, but not effective in protecting the kidneys from injury. 2.The effect of rhEGF promoting the recovery of gcntamicin- induced toxic ATN may be related to the inhibition of apoptosis and the promotion of expression of small weight heat shock proteins. 3.The effect of rhEGF promoting the recovery of gcntamicin-induccd toxic ATN may be related to the animal model of certain damage degree and the doses of rhEGF. 4.The dynamic analysis of urine EGF level can be used as a reference in the understanding of course of renal failure and the evaluation of the curative effect of medicine.