Objective:To investigate the protective effects of active ingredients of Sinomenine on the kidneys of db/db mice with Diabetes Mellitus(DM)and its underlying mechanisms.Methods:Thirty 6-week-old male db/db mice were randomly divided into five groups:a model group(treated with equal volume of saline),a positive group(treated with 195 mg/kg/d calcium dobesilate),and low,medium,and high-dose groups of Sinomenine Hydrochloride(SH)(treated with 31.2,62.4,and 124.8 mg/kg/d SH,respectively).Six age-matched db/m mice were selected as the control group and received an equal volume of saline.All mice were administered by ga-vage once daily for 6 consecutive weeks.At the end of 12 weeks,the general conditions of mice in each group were observed,and levels of urinary microalbumin(mAlb),serum creatinine(SCr),and blood urea nitrogen(BUN)were measured.Kits were used to detect the levels of malondialdehyde(MDA),reduced glutathione(GSH),and superoxide dismutase(SOD)in renal tissue homogenates;Luminex multi-factor detection technology to determine serum levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-10(IL-10);ELISA to measure serum levels of immunoglobulin G(IgG),immunoglobulin M(IgM),immuno-globulin A(IgA),and complement protein 3(C3);Hematoxylin-eosin(HE)and periodic acid-Schiff(PAS)staining to observe the renal histopathological changes;and transmission electron microscopy to observe the renal ultrastructural changes.Results:Compared with the model group,the levels of mAlb,SCr,and BUN in the positive group and the low,medium,and high-dose SH groups were all decreased(P<0.05);The level of MDA in renal tissue homogenates was decreased(P<0.05),while the levels of GSH and SOD activity were increased(P<0.05);The serum levels of TNF-α,IL-1β,IL-6,IgG,IgM,IgA,and complement C3 were all decreased(P<0.05),while the level of IL-10 was increased(P<0.05);The glomerular injury and tubular epithelial edema were improved,and the renal tissue damage observed under the microscope was reduced.Conclusion:The active ingredients of Sinomenine have a protective effect on the kidneys of diabetic db/db mice,and its mechanism may be related to improving oxidative stress response,alleviating inflammatory re-sponse,and enhancing immune function.
Sinomeninedb/db mice with DMoxidative stressinflammatory responseimmune function