To investigate the in vivo therapertic effects of Cordyceps Sinensis in CsA-incuced nephrotoxicity in rats,and to evaluate the effects of different ingredients isolated from Cordyceps Sinensis in promoting cultured human tubular epithelial cells proliferation and preventing CsA cytotoxicity in vitro. METHODOLOGY In vivo studies,CsA nephrotoxicity was induced in rats by high dosage CsA subcutaneous injection(15 mg/kg·d).Cordyceps Sinensis was given by gavage dayly after CsA injection.Kidney function,biochemical parameters and histopathology were examined four weeks later.In vitro studies,ingredients of different molecular weight isolated from Cordyceps Sinensis were used.Human kidney proximal tubular cell(HKC)proliferation was dectected by 3H-TdR incorporation and cell cycle analysis.LDH level in culture supernatant was dectected.Intracellular EGF and c-met mRNA expression was quantitated by RT-PCR assay. RESULTS In vivo studies,at the fourth week of observation,rats injected with CsA showed significantly elevated serum creatitinine,blood urea nitrogen(BUN),sodium level and markedly decreased serum albumin and creatinine clearance rate.
Urinary NAG and lysozyme excretion elevated significantly.Histopathology revealed pachy tubular vacuolization at the second week,and pachy tubular atrophy at the fourth week.In Cordyceps Sinensis treated group,urinary NAG and lysozyme excretion,creatinine clearance rate were ameliorated markedly at the end of the experiment.Among the different ingredients from Cordyceps Sinensis,low molecular weight water extractant was the most potent in promoting HKC proliferation,as well as in the prevention of CsA-induced HKC cytotoxicity in vitro.EGF and c-met mRNA expression were not increased in HKC cells stimulated with Cordyceps Sinensis. CONCLUSION Cordyceps Sinensis can ameliorate CsA-induced nephrotoxicity in rats.Low molecular weight water extractant is the most potent in promoting HKC proliferation in vitro.