糖络宁对高糖环境下雪旺细胞铁死亡的作用OA

Objective To investigate the effects of Tangluoning on the expression of ferritin,ferritin light chain(FTL),and heme oxygenase-1(HO-1),iron filament network-associated proteins,in Schwann cells(SCs)under high glucose environment.Methods RSC96 cells were exposed to 150 mmol/L glucose and allocated into three groups:blank control,high-glucose,and Tangluoning treatment.Both the high glucose group and the Tangluoning group were exposed to 150 mmol/L glucose;the Tangluoning group additionally received treatment with drug-containing serum,while the blank and high glucose groups were administered an equal volume of blank serum.Lipid-peroxidation-derived malondialdehyde(MDA)was measured using a colorimetric assay.The expression levels of ferroptosis-related proteins,including Ferritin,FTL,and HO-1,in SCs under high-glucose conditions(24 h and 48 h)were assessed by high-content analysis.A hyperglycemic model was established in SD rats by intraperitoneal injection of streptozotocin and maintained for 12 weeks to induce diabetic peripheral neuropathy(DPN).The rats were then randomly assigned to normal control,model,and Tangluoning treatment groups(n=6).After 12 weeks of intervention,the expression of Ferritin,FTL,and HO-1 in sciatic nerve tissues was evaluated by immunofluorescence(IF).Results The colorimetric assay results in SCs showed that compared to the control group,the MDA content in the high-glucose group was significantly increased(P＜0.01).In contrast,compared to the high-glucose group,the MDA content in the Tangluoning group was significantly decreased(P＜0.01).High Content Screening revealed that at 24 h post-treatment,compared with the control group,the expression of HO-1,FTL,and Ferritin was significantly elevated in the high-glucose group(P＜0.01).Compared with the high-glucose group,the expression of FTL and Ferritin in the Tangluoning group was significantly reduced(P＜0.01),while the expression of HO-1 was significantly in-creased(P＜0.01).At 48 h,the expression of Ferritin,FTL and HO-1was significantly higher in the high-glucose group than in the control group(P＜0.01 or P＜0.05).IF results in sciatic nerve showed that,compared with the normal control group,the expression of HO-1 and Ferritin was significantly increased in the model group(P＜0.01),while the expression of FTL was significantly decreased(P＜0.01).Compared with the model group,the expression of Ferritin in the Tangluoning group was significantly decreased(P＜0.01),whereas the expression of FTL and HO-1 was significantly increased(P＜0.01,P＜0.05).Conclusion Tangluoning can reduce ferroptosis in SCs by inhibiting the expression of FTL protein under high-glucose environment,thereby decreasing the synthesis of Ferritin.Additionally,it can also upregulate HO-1 protein expression,activating endogenous antioxidant stress pathways to effectively counteract mitochondrial oxidative stress.Moreover,Tangluoning also increases FTL levels in the sciatic nerve,suggesting that it may exert neuroprotective effects by regulating iron homeostasis and alleviating oxidative damage caused by iron accumulation.These findings provide new insights into the role of Tangluoning in treating DPN.