RESUMO
Objective To study the therapeutic effect of bitter gourd saponins on salt-sensitive kidney injury induced by high salt diet and its possible mechanism.Methods 50 Sprague Dawley (SD) rats were randomly divided into normal group,model group and low-dose,middle-dose and high-dose treatment group after 10 days of adaptive feeding.Each group had 10 rats.Except the normal group,the other four groups were given high salt diet (4.0％ high salt diet) to induce salt-sensitive kidney damage in rats.The normal group and the model group were given 1.0 m/(kg · d) normal saline,and the three dosage groups of total saponins of balsam pear were given 10 mg/(kg · d),20 mg/(kg · d) and 40 mg/(kg · d) respectively.After 8 weeks of treatment,rats were sacrificed and collect the 24-hour proteinuria,creatinine.Serum creatinine,serum aldosterone,serum sodium and serum potassium were measured,and renal histopathology and the expression of podocin and nephrin were detected.Results Pathological examination of model group showed obvious glomerular sclerosis and renal interstitial fibrosis,and glomerular sclerosis in the treatment group was obviously improved by bitter gourd saponins;The systolic pressure in the model group was 170 mmHg,significantly higher than that of the normal and treatment groups,the systolic blood pressure of the treatment groups were obvious decreased when treated by bitter gourd saponins (P ＜ 0.05);Compared with normal group,serum creatinine and 24 h proteinuria / urine creatinine in model group were significantly increased (P ＜ 0.05),while creatinine clearance rate and aldosterone were significantly decreased (P ＜ 0.05),and the above indexes in bitter gourd saponins treatment group were significantly improved;Compared with the model group,the protein and mRNA expression of podocin and nephrin were significantly decreased (P ＜ 0.05),while the two indexes can be revered by bitter gourd saponins in treatment group (P ＜ 0.05).Conclusions The bitter gourd saponins can significantly improve the symptoms of salt-induced hypertensive nephropathy in rats,which may be related with the expression of podocin and nephrin in renal tissue,thereby inhibiting glomerulosclerosis and improving renal interstitial fibrosis.
RESUMO
Objective To investigate the dynamic changes of endoplasmic reticulum stress-related molecules including glucose regulated protein (GRP78), C/EBP homologous protein (CHOP), and caspase-12 in sciatic nerve of diabetic rats and explore its mechanisms.Methods Rats were randomly divided into normal control group (NC) and diabetes mellitus group (DM) that were induced by intraperitoneal injection of Streptozocin after 4 weeks of high-fat chow feeding.Sciatic nerves were isolated for three times at 4 weeks, 8 weeks and 12 weeks after induction of diabetes.The expressions of GRP78, CHOP,and caspase-12 were detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.The morphology of sciatic nerve was investigated with electron microscope.Results With the extension of the course, demyelinating and axonal injury appeared in sciatic nerve of diabetic rats.The expressions of GRP78 mRNA and protein in DM group were significantly higher than NC group at 4 weeks and 8 weeks after induction of diabetes(P ＜0.05, P ＜0.01).The expressions of CHOP mRNA and protein in DM group were significantly higher than NC group at 8 weeks and 12 weeks after induction of diabetes (P ＜ 0.05).The expressions of caspase-12 mRNA and protein in DM group were significantly higher than NC group at 8 weeks after induction of diabetes(P ＜ 0.05, P ＜ 0.01).Conclusions Endoplasmic reticulum stress-related molecules (GRP78, CHOP, and caspase-12) contributed to the peripheral nerve injury of diabetic rats, and displayed dynamic changes.