Abstract:
0bjective To study the effect of alpha-mangostin on inhibiting acid sphingomyelinase (ASMase)and endoplasmic reticulum stress signaling pathway under high glucose in mouse mesangial cells (MES13) apoptosis.Methods Synchronized MES13 were divided into following groups:(1) NG group (normal concentration of glucose group, 5.5mmol/L glucose); (2)NG+ a-M group (normal concentration of glucose + alpha-mangostin group); (3) HG group (high concentration glucose group, 30mmol/L); (4)HG+ low concentration of a-M group (HG+1μM alpha-mangostin); (5)HG+ medium concentration a-M group (HG+2μM alpha-mangostin); (6)HG+ high concentration of a-M group (HG+4μM alpha-mangostin); (7)HG+des group (HG+ desipramine). Cells were cultured for 24 hours, and cell activity was detected by cck-8 assay. cell apoptosis was detected by flow cytometry. The protein ex<x>pressionlevels of ASMase, GRP78, p-PERK, ATF4, CHOP and caspase12 were detected by western blot. Results 1. Compared with NG group, the apoptosis level of MES13 cells in HG group was significantly increased (P<0.05). Compared with HG group, the apoptosis rate of HG+ a-M group was decreased. 2. Compared with NG group, the ex<x>pression of ASMase protein in MES13 cells in HG group was significantly increased (P<0.05), and the ex<x>pression of ASMase protein was decreased in HG+ a-M group compared with HG group (P<0.05). 3. Compared with NG group, the ex<x>pression levels of GRP78, p-PERK, ATF4, CHOP and caspase12 were significantly increased in HG group (P<0.05). Compared with HG group,the ex<x>pression levels of GRP78, p-PERK, ATF4, CHOP and caspase12 were significantly decreased in HG+ a-M group (P<0.05). Conclusion Alpha-mangostin may reduce the endoplasmic reticulum stress signal pathway by inhibiting the ASMase activated by high glucose, so as to alleviate the apoptosis of MES13 cells cultured in high glucose.This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy