SGLT2抑制剂对糖尿病小鼠炎性因子表达的影响

Effect of SGLT 2 inhibitor on the expression of inflammatory factors in diabetic mice

目的探讨糖尿病小鼠血管内皮炎性因子是否表达,SGLT2抑制剂对其作用的影响。方法将8周龄SPF级雄性CIR小鼠腹腔注射低剂量STZ(50 mg/kg),建模持续6 d,对照组皮下注射生理盐水,造模成功,随机分成对照组(普通饲料),模型组(普通饲料)和治疗组(普通饲料+达格列净干预治疗),动态观察4周、8周、12周末小鼠的体重、血糖变化,分别应用EILSA法检测血浆内肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、单核细胞趋化因子-1(MCP-1)表达变化和Western blot法测定血管壁各炎性因子蛋白的表达。结果各组小鼠体重和血糖在不同时间段比较,差异有统计学意义(P<0.05)。与对照组比较4周模型组血浆内TNF-α显著升高,差异有统计学意义(P<0.01),而4周模型组血浆内IL-1β、MCP-1表达亦增多,差异无统计学意义(P>0.05);与对照组比较8周、12周模型组血浆内TNF-α、IL-1β、MCP-1表达变化明显升高,差异有统计学意义(P<0.05);与模型组比较4周治疗组血浆内TNF-α、IL-1β、MCP-1表达变化不明显,差异无统计学意义(P>0.05);与治疗组比较8周、12周时模型组血浆内TNF-α、IL-1β、MCP-1表达变化明显下降,差异有统计学意义(P<0.05)。12周末血管壁组织内各炎性因子蛋白表达有变化,差异有统计学意义(P<0.05)。结论SGLT2抑制剂能有效抑制糖尿病小鼠血管内皮细胞内炎性因子的释放。

Objective To investigate the effect of SGLT2 inhibitor on vascular endothelial inflammatory factors in diabetic mice.Methods 8-week-old CIR mice were injected intraperitoneally with low-dose STZ(50 mg/kg)to establish a diabetic model,and the modeling lasted for six days.The control groups were injected subcutaneously with normal saline,the model group(common feed),and the treatment group(common feed)&dapagliflozin intervention treatment.Body weight and blood glucose changes were observed at the end of 4w,8w,and 12w.The expression of TNF-a,IL-1β,and MCP-1 in plasma was detected by the EILSA method,and the expression of inflammatory factors in the vascular wall was detected by Western blot.Results There were significant differences in body weight and blood glucose(P<0.05).Compared with the control group,the expression of TNF-a in the 4W model group increased significantly(P<0.01).However,the expression of IL-1βand MCP-1 in the 4W model group increased,but there was no significant difference(P>0.05).TNF-a,IL-1β,and MCP-1 levels in plasma were significantly increased in the model groups of 8w and 12w(P<0.05).Compared with the model group,the expression of TNF-a,IL-1β,and MCP-1 in the plasma of the treatment group did not change significantly at 4w(P>0.05).At the 8w and 12w,the expression of TNF-a,IL-1β,and MCP-1 in the plasma of the model group decreased significantly(P<0.05).The expression of inflammatory factor protein in vascular tissue was changed in the 12w(P<0.05).Conclusions SGLT2 inhibitors effectively inhibited the release of inflammatory factors from the endothelium of diabetic mice.